BMC Infectious Diseases 2016, Volume 16 Suppl 3
DOI 10.1186/s12879-016-1480-8
MEETING ABSTRACTS
Open Access
Proceedings of The 8th Romanian National
HIV/AIDS Congress and The 3rd Central
European HIV Forum
Sibiu, Romania. 5-7 May 2016
Published: 27 June 2016
ORAL PRESENTATIONS
Session title: epidemiology, subtypes, regional
issues
O1
HIV-1 diversity in Bulgaria (current molecular epidemiological
picture)
Ivailo Alexiev1, Reneta Dimitrova1, Anna Gancheva1, Asya Kostadinova1,
Mariyana Stoycheva2, Daniela Nikolova3, Ivaylo Elenkov4
1
National HIV Reference Laboratory, National Center of Infectious and
Parasitic Diseases, Sofia, Bulgaria; 2Department of Infectious Diseases,
Medical University, Plovdiv, Bulgaria; 3Clinic of Infectious Diseases,
Medical University, Varna, Bulgaria; 4Hospital for Infectious and Parasitic
Diseases, Sofia, Bulgaria
Correspondence: Ivailo Alexiev (ivoalexiev@yahoo.com) – National HIV
Reference Laboratory, National Center of Infectious and Parasitic
Diseases, Sofia, Bulgaria
BMC Infectious Diseases 2016, 16(Suppl 3):O1
Objectives
In Bulgaria 1606 cases with HIV/AIDS were diagnosed from 1986 until
2012. Epidemiological data indicated greater heterogeneity of HIV-1
positive population, including minority groups, migrants, and recent increase of men who have sex with men (MSM) and intravenous drug
users (IDUs). The aim of the present study was to investigate the current
molecular epidemiological picture of HIV-1 diversity among different
transmission groups in Bulgaria.
Materials and Methods
HIV-1 diversity was analyzed in 637 (39.7 %) of all HIV/AIDS patients in
the country. HIV-1 pol sequences were generated with TruGene and/or
ViroSeq Genotyping Systems. The sequence alignment contained Bulgarian sequences and reference sequences from Los Alamos and GenBank.
Phylogenetic relationships were inferred by ML and Bayesian analysis.
Recombinations were analyzed with bootscan analysis using SimPlot
software.
Results
The most prevalent HIV-1 strain in the studied population was found to
be subtype B 38.8 %. That strain was followed by CRF01_AE 20.3 %,
CRF02_AG 13.8 %, subtype C 3.6 %, subtype A1 1.6 % and the rest of
strains were defined as 3 different HIV-1 subtypes (F, G and H) and 7 circulating recombinant forms (05_DF, 14_BG, 03_AB, 04_cpx, 12_BF,
33_01B and 36_cpx). In addition, 30 different unique recombinant forms
consisting of 18.2 % were identified. We found that unlike in the most
European countries, where subtype B is dominating, non-B HIV-1 subtypes were the most prevalent in Bulgaria. Phylogenetic analysis showed
multiple clusters demonstrating rapid development of sub-epidemics in
different transmission groups. In addition, unequal distribution of HIV-1
clades across different regions and transmission groups of the populations were found. Moreover, we found that various viral clades were introduced in Bulgaria from abroad by migrants.
Conclusions
Our analysis revealed wide HIV-1 diversity and unequal distribution of
different strains among MSM, IDUs and heterosexual individuals. Phylogenetic analysis showed multiple clusters demonstrating development
of local-epidemics. Significant number of HIV-1 clades were introduced
from abroad by migrants. Our findings indicated that providing of detailed molecular epidemiological surveillance of HIV-1 in Bulgaria is of
great importance to better understand the epidemic in the country.
O2
Knowledge, attitudes and practices of the general population on
HIV/AIDS, hepatitis B and C in Romania
Cătălin Tilișcan1,2, Mioara Predescu1, Bogdan Păunescu3, Anca StreinuCercel1,2, Oana Săndulescu1,2, Claudiu Mihai Șchiopu1, Mădălina
Hristache1, Lăcrămioara Aurelia Brîndușe4, Adrian Streinu-Cercel1,2
1
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest,
Romania; 2Carol Davila University of Medicine and Pharmacy, Bucharest,
Romania; 3Totem Communications, Bucharest, Romania; 4National
Institute of Public Health, Bucharest, Romania
Correspondence: Cătălin Tilișcan (catalin.tiliscan@gmail.com) – National
Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O2
Background
Hepatitis B (HBV), hepatitis C (HCV) and HIV infections are important global public health issues. Assessing the level of knowledge, attitudes and
practices regarding HIV, HBV and HCV infections in the general population represents a very important basis for an effective strategy that aims
to inform and raise awareness in this field.
Methods
The study was based on two query methods: an opinion poll and a face
to face interview based on a questionnaire applied by the interview operator to two target populations – adults over 18 years of age from
general population and injecting drug users from Bucharest. There
were two sample groups - a probabilistic, bistadial, stratified group consisting of 1005 respondents from the general population (GP) and a
group of 200 injecting drug users (IDUs). The questionnaires were processed by TOTEM Communications during August-September 2015.
Results
Most respondents know about HIV/AIDS and hepatitis B and C. One
of five respondents from the general population considers that hepatitis B/C is caused by lack of hygiene compared to only 1 % of IDUs.
In terms of transmission risks, IDUs have higher knowledge on ways
of transmission of HIV/AIDS, HBV, HCV as they benefitted from detailed information in this area. Three quarters of IDUs shared injecting equipment with other persons. Persons from the general
population living in rural areas shared needles with other persons
more than their peers in urban locations. Approximately a third of respondents from the general population are comfortable around a
person infected with HIV/HBV/HCV compared with over eight out of
© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
BMC Infectious Diseases 2016, Volume 16 Suppl 3
ten IDUs. Half of the respondents from the GP would conceal that
one of their kin is infected with HIV. Two of ten respondents from GP
and three out of ten IDUs consider that a child infected with HIV
should not be granted access to school. Almost three quarters of respondents disapprove of a teacher’s academic career if he or she is
infected with HIV, HBV or HCV. Three quarters of respondents in the
target populations would get a vaccine against HBV.
Conclusions
We noted significant differences between GP and IDUs regarding
knowledge and attitudes on HIV, HBV and HCV infections.
Acknowledgement
This study is part of the RO 19.02. Project “Strengthening the prevention and
control of HIV/AIDS, HBV, HCV in Romania”, financed by the Norway Financial
Mechanism 2009-2014, “Public Health Initiatives”.
O3
The prevalence of human leukocyte antigen-B*57:01 allele carriers
and CXCR4 tropism among newly diagnosed HIV infected patients
in Serbia
Marija Todorovic1, Marina Siljic1, Dubravka Salemovic2, Valentina Nikolic1,
Ivana Pesic-Pavlovic3, Jovan Ranin1,2, Djordje Jevtovic1,2, Maja Stanojevic1
1
University of Belgrade Faculty of Medicine, Belgrade, Serbia; 2Infectious
and Tropical Diseases University Hospital, Clinical Center Serbia, HIV/AIDS
Unit, Belgrade, Serbia; 3Virology Department, Clinical Center Serbia,
Belgrade, Serbia
Correspondence: Marija Todorovic (mtodorovic5@gmail.com) –
University of Belgrade Faculty of Medicine, Belgrade, Serbia
BMC Infectious Diseases 2016, 16(Suppl 3):O3
Background
Abacavir is an effective antiretroviral drug, among the most commonly used nucleoside reverse transcriptase inhibitor (NRTI) in
Serbia. Although generally well tolerated, a percentage of patients
experience a potentially life-threatening hypersensitivity reaction
(HSR), shown to be associated with the presence of the class I MHC
allele, HLA B*57:01. Genotyping for HLA B*57:01 prior to starting abacavir is nowadays recommended in international HIV treatment
guidelines for avoiding abacavir-induced HSR. On the other hand,
CCR5 (R5) tropic viruses are known to be associated with early stages
of infection, whereas CXCR4 (X4) HIV-1 tropic strains prevail in advanced infection. Recently, a change in the genotype-predicted tropism frequency in early disease has been described with increased
frequency of non R5 strains. The aim of our study was to estimate
the prevalence of HLA B*57:01 allele and genotype-predicted viral
tropism among newly diagnosed HIV-1 infected patients in Serbia.
Methods
The presence of HLA B*57:01 allele was analyzed in 273 HIV-1 infected
patients aged 18 or more, who were abacavir naive. Buccal swab samples were obtained from all participants and assayed for the presence
of HLA B*57:01 using a commercial HLA B*57:01 real time PCR kit. Baseline plasma samples were used to assess the HIV-1 genotypic tropism
with triplicate V3-loop sequencing. The non-R5 tropism prediction
thresholds were assigned using a false positive rate (FPR) of 10 %.
Results
The presence of HLA B*57:01 allele was found in 22 of 273 tested individuals (8 %, 95 % CI 5.4-11.9 %). The overall non-R5 tropism frequency was 15.4 %.
Conclusions
Abacavir still remains one of the key drugs of antiretroviral regimens
against HIV-1 in Serbia as in other countries. This is the first study
that estimated HLA-B*57:01 prevalence in Serbia. Very high prevalence of HLA B*57-01 found in our study, strongly supports HLA
B*57:01 genotyping that should be implemented prior to initiation of
abacavir containing therapy to reduce the risk of potentially life
threatening hypersensitivity reaction. R5 tropism predominates
among the treatment of naive individuals, however, the frequency of
non-R5 tropic variants needs to be monitored.
Page 2 of 29
Acknowledgement
This work was partially funded by the Ministry of Education and Science
Republic of Serbia (grant MNTR175024).
O4
HIV transmission among stable serodiscordant couples from the
former Pediatric Cohort follow up in the National Institute of
Infectious Diseases
Ana Maria Tudor1,2, Delia Vlad1, Mariana Mărdărescu1, Sorin Petrea1,
Cristina Petre1, Ruxandra Neagu-Drăghicenoiu1, Rodica Ungurianu1, Alina
Cibea1, Odette Chirilă1, Cristian Anghelina1, Ileana Coserea1
1
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest,
Romania; 2Carol Davila University of Medicine and Pharmacy, Bucharest,
Romania
Correspondence: Ana Maria Tudor (tudoranamaria@yahoo.com) –
National Institute for Infectious Diseases “Prof. Dr. Matei Balș” Bucharest,
Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O4
Background
In the last years, patients from the former Romanian Pediatric Cohort
engaged in stable couples. Some of those couples are serodiscordant. Our aim is to evaluate the risk of HIV transmission among those
patients.
Methods
We retrospectively collected the data on results of HIV tests performed in patients’ partners followed up in the Pediatric HIV Department between 2012 and 2015. We also collected the data on viral
load in HIV positive patients and the declared use of condoms in
studied partners.
Results
We identified 81 serodiscordant couples, in 70 couples one partner
was part of the former Pediatric Cohort. The incidence of HIV infection in patients’ partners was 2.4 % (2/81cases). In these two couples,
the male partner was diagnosed with HIV in early childhood, but at
the moment of partner diagnosis the viral load was high (5log10),
since they refused the antiretroviral treatment. In our study 35/81
(43.2 %) of discordant couples the male was positive. During the
studied period we encountered 33 pregnancies. Just one couple
used safe methods of conception, sperm washing. The use of condoms was declared in 24 discordant couples. 8 out of 35 (22.8 %)
HIV positive males and 17 out of 49 (34.7) positive females declared
the use of condoms.
Conclusions
One third of our patients used condoms in HIV discordant couples,
but we found only 2 cases of transmission. We need to focus more
on education for HIV prevention and safe conception in our patients
in the context of patients’ desire of starting a traditional family.
O5
Unemployment is associated with syringe sharing among people
who inject drugs in Greece
Pantelia-Amalia Krikelli1, Eirini Pavlitina2, Mina Psichogiou3, Demetris
Lamnisos1, Leslie Williams4, Anya Korobchuk5, Britt Skaathun6,
Pavlo Smyrnov5, John Schneider6, Vana Sypsa7, Dimitrios Paraskevis7,
Angelos Hatzakis7, Samuel R. Friedman4, Georgios K. Nikolopoulos2,8
1
European University of Cyprus, Nicosia, Cyprus; 2Transmission Reduction
Intervention Project, Athens, Greece; 3Laikon General Hospital,
Department of Propedeutic Medicine, Athens, Greece; 4National
Development and Research Institutes, New York, NY, USA; 5Alliance for
Public Health, Kyiv, Ukraine; 6University of Chicago Medical Center,
Center for AIDS Elimination, Chicago, IL, USA; 7Medical School, University
of Athens, Athens, Greece; 8Hellenic Centre for Disease Control and
Prevention, Amarousio, Greece
Correspondence: Dimitrios Paraskevis (dparask@med.uoa.gr) – Medical
School, University of Athens, Athens, Greece
BMC Infectious Diseases 2016, 16(Suppl 3):O5
BMC Infectious Diseases 2016, Volume 16 Suppl 3
Background
Greece has been hit hard by a serious economic and social crisis. An
HIV outbreak among people who inject drugs (PWID) started early in
2011 and resulted in more than 1000 new diagnoses by 2013. This
work studied the association between needle/syringe sharing and
unemployment and homelessness, which comprise two salient characteristics of economic instability.
Methods
Data on PWID were collected by a social network tracing project (Transmission Reduction Intervention Project - TRIP). Baseline interviews were
conducted between June 2013 and July 2015 in Athens, Greece. The
statistical analyses included chi-squared test and logistic regression modeling. The multivariable models included age, sex, level of education, nationality, employment, homelessness, married status, sexual orientation,
years of injection and knowledge about recent HIV infection.
Results
322 PWID (mean age 35.7 ± 8 years, females 18.9 %) were interviewed.
The proportion of PWID who reported they never used syringes someone else had used before was 64 %. The proportion of never sharing
was lower among participants who were non-Greeks (41.9 %) vs.
Greeks (66.3 %, p = 0.05), homeless (52.6 %) vs. with stable accommodation (67.5 %, p = 0.07), without a job (69.1 %) or unable to work because of drug use or illness (57.4 %) vs. those who were employed
(81.3 %; p = 0.05), and with elementary education (55.6 %) vs. high
school (67 %) or university graduates (85.7 %, p = 0.26). Age, education
level and employment retained their significance in multivariable logistic regression. The adjusted odds ratios (OR) for never sharing were: for
the unemployed vs. the employed: 0.36; 95 % Confidence Interval (CI):
0.17-0.79; for age (per year increase) 1.05; 95 % CI: 1.02-1.08; and for
high school/university education vs. elementary 1.68; 95 % CI: 1.02-2.74.
Conclusion
Needle/syringe programs scaled-up after the start of the outbreak in
2011 but unemployed PWID in 2013-2015 were 64 % less likely to report they never shared syringes than PWID who were economically
active. The unemployment rate in Greece is higher than 25 % and
shows no signs of decreasing. Efforts to help PWID get a job may reduce risky behaviors among PWID in an unstable setting, and following a serious HIV outbreak.
Funding
US National Institute on Drug Abuse (NIDA) (Grant: DP1 DA034989
and Hellenic Scientific Society for the Study of AIDS and STDs).
ORAL PRESENTATIONS
Session title: comorbidities, ageing with HIV
O6
Correlation of adipocytokine levels in different types of
lipodystrophy in HIV/AIDS patients
Gordana Dragović1, Danica Srdić1, Al Musalhi Khawla2, Ivan Soldatović3,
Jelena Nikolić4, Djordje Jevtović4, Devaki Nair2
1
Department of Pharmacology, Clinical Pharmacology and Toxicology,
School of Medicine, University of Belgrade, Belgrade, Serbia;
2
Department of Clinical Biochemistry, Royal Free Hospital and University
College London, London, United Kingdom; 3Institute for Biomedical
Statistics, School of Medicine, University of Belgrade, Belgrade, Serbia;
4
Infectious and Tropical Diseases Hospital, School of Medicine, University
of Belgrade, Belgrade, Serbia
Correspondence: Gordana Dragović (gozza@beotel.net) – Department
of Pharmacology, Clinical Pharmacology and Toxicology, School of
Medicine, University of Belgrade, Belgrade, Serbia
BMC Infectious Diseases 2016, 16(Suppl 3):O6
Background
Combination antiretroviral therapy (cART) can induce metabolic complications including lipodystrophy, dyslipidemia, and insulin resistance in HIV-infected patients. Adipokines may play important roles in
these alterations, especially in lipodystrophy. The aim of this study
was to evaluate the relationship between serum levels of adipocytokines in four different categories of fat distribution: lipoatrophy
Page 3 of 29
(LA), lipohypertrophy (LH), mixed fat redistribution (MFR) and nolipodystrophy in HIV-infected patients.
Methods
Cross-sectional study of 66 HIV-infected adults. Levels of adiponectin,
resistin, leptin, interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10),
plasminogen-activator-inhibitor-1 (PAI-1), C-peptide, cystatin-C, tumor
necrosis factor alpha (TNF-α), vascular-endothelial-growth-factor (VEGF),
epidermal-growth-factor (EGF), interferon-gamma (IFN-γ) and monocytechemoattractant-protein-1 (MCP-1) were measured. Differences between
groups were tested using t-test and Mann-Whitney test, and analysis of
covariance to examine relationship between adiponectin and leptin and
lypodystrophy categories adjusted for confounding variables.
Results
The lipodystrophy was observed in 29 (44 %) patients, while 15 (52 %)
of them had LA, 4 (14 %) had LH and 10 (34 %) patients had MFR. LH
patients had higher levels of adiponectin (p = 0.011), leptin (p = 0.039),
cystatin-C (p = 0.001), IL-6 (p = 0.065), and lower levels of IL-4 (p =
0.052). LA patients had lower levels of IL-4 (p = 0.043), IL-10 (p = 0.031)
and IL-1α (p = 0.051). Correlation of adiponectin with lipodystrophy remains statistically significant in the subgroup of patients with lipohypertrophy after adjustment for age, BMI, cystatin-C, PAI-1, IFN-γ (p = 0.001).
Conclusions
Adiponectin was shown to be an important marker in fat disturbances in patients undergoing cART and directly associated with
lipohypertrophy, and could be the possible target for new therapeutic strategies in HIV/AIDS patients.
O7
IP10 – a possible biomarker for the progression of HIV infection
Aura Temereanca1,2, Adelina Rosca1,2, Luminita Ene3, Benchawa
Soontornniyomkij4, Carmen Diaconu2, Claudia Dita2, Cristian Achim4,
Simona Ruta1,2
1
Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;
2
“Stefan S. Nicolau” Institute of Virology, Bucharest, Romania; 3“Dr Victor
Babeș” Hospital for Infectious and Tropical Diseases, Bucharest, Romania;
4
University of California San Diego, La Jolla, San Diego, CA, USA
Correspondence: Aura Temereanca (auratemereanca@yaoo.com) –
Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O7
Background
IP10 (interferon gamma-induced protein) is associated with chronic
immune activation and HIV-1 viral replication. Our study evaluates
the relationship between IP10 and immunologic and virologic status
in a group of extensively-treated HIV-infected Romanian patients,
long term survivors.
Materials and methods
90 HIV+ subjects (median age: 23 years, males: 53.3 %) with a median duration on cART of 12 years were included. Paired plasma and
CSF samples were available for 45 patients. Current median HIV viral
load and CD4 count were 1.53 log10 HIV RNA copies/mL and 464.16
cells/cmm (range 2-1720), respectively. 43 % had undetectable viral
load and 38 % had CD4 > 500 cells/cmm. Plasma and CSF concentration of IP-10 was measured using multiplex assay on the Meso Scale
Discovery platform (Meso Scale Diagnostics, LLC. Gaithersburg, MD).
Patients were classified into two groups based on the median threshold value of IP10 (median = 444 pg/mL; IQR = 296-756 pg/mL): group
1 with higher and group 2 with lower values, respectively.
Results
Plasma and CSF IP10 levels were positively correlated with HIV viral
load (rho = 0.54, p < 0.001; rho = 0.58, p < 0.002) and the degree of
immune suppression (rho = 0.45, p < 0.001; rho = 0.32, p < 0.03). The
group of patients with higher plasma and CSF IP10 levels had significantly higher median HIV RNA (0 log copies/mL vs. 2.46 log copies/
mL; p < 0.001) and significantly lower median time from VL Zenith (5
vs. 8 years; p = 0.01). Elevated IP10 levels were associated with lower
CD4 T-cell counts (419 vs. 663 cells/cmm, p < 0.001) and lower
CD4:CD8 ratio (57 % vs. 36 %, p = 0.03). No differences were observed among the 2 groups in terms of sex, median age, CD4 count
nadir, AIDS-defining events (stage C) and cumulative ART exposure.
BMC Infectious Diseases 2016, Volume 16 Suppl 3
Patients with active viral replication (HIV viral load > 1000 copies/mL)
had significantly higher concentrations of IP10 in both plasma and
CSF compared with those presenting undetectable HIV RNA (1007 vs.
376 pg/mL, p < 0.0001; 4943 vs. 557 pg/mL, p = 0.04).
Conclusions
Elevated IP10 levels are associated with high viral load and immune
suppression in heavily-treated HIV-infected Romanian patients, suggesting that IP10 could be a marker of HIV-1 disease progression.
O8
A permanent challenge: persistent low viremia in HIV positive
patients on ART
Șerban Benea1,2, Ruxandra Moroti1,2, Raluca Jipa1, Eliza Manea1, Andrada
Stan1, Elisabeta Benea1,2, Dan Oțelea1, Adriana Hristea1,2
1
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest,
Romania; 2Carol Davila University of Medicine and Pharmacy, Bucharest,
Romania
Correspondence: Șerban Benea (serbanb_16@yahoo.com) – National
Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O8
Background
With new and potent antiretroviral drugs, the goal of maintaining a
HIV viral load below the limits of assay detection seems to be within
reach. Nevertheless, persistent low-level viremia (LLV) remains a challenge for clinicians, with unclear consequences regarding virologic
failure and resistance mutations.
The main goal of our study was to identify and describe characteristics associated with persistent low-level viremia in HIV infected patients from one department.
Methods
We performed a retrospective, descriptive study, analyzing the records of HIV infected patients in our department, Adult Clinic IV of
the National Institute for Infectious Diseases “Prof. Dr. Matei Balș”
over a period of 15 years (2001-2015). The inclusion criteria for our
patients were: antiretroviral therapy (ART) for more than 24 weeks,
with two consecutive detectable viral loads (VL) of >20 and <1000
copies/mL. We analyzed demographical data, CDC stage, the
immune-virological status (last evaluation and at baseline), ART regimen (drugs used and duration).
Results
Out of 153 patients monitored in our department, 143 (93.4 %) are
on ART. Eighty-seven (60.8 %) patients on ART had undetectable VL
at the last evaluation, including 23 of them (26.4 %) that had at least
one episode of persistent LLV followed by undetectable VL and 18
(20.6 %) had one or more VL blips. Fifty-six patients had detectable
VL at the last evaluation in 2015. Eighteen (12.6 %) of patients on
ART met the inclusion criteria for our study. Most patients (66.6 %,
n = 12) were men and the median age was 39 years. Based on CDC
classification 4 patients (22.2 %) were A, 8 (44.4 %) were B and 6
were C (33.3 %). The median nadir CD4 cell count was 172 cells/cmm
(IQR, 86-240) and the median baseline VL was 5.66 log10 (IQR, 5.09
log10-6.38 log10). The median duration of ART was 36 months (IQR,
12-96). Our patients received a median number of 2 (IQR, 1-4) ART
regimens. Only 7 (39 %) patients had at least one undetectable VL
while on ART. At the moment of our study, all patients were on a
regimen containing two NRTIs combined with: a PI (boosted- lopinavir, n = 3; boosted-atazanavir, n = 3, boosted-darunavir, n = 10), an
integrase inhibitor (n = 1) or a NNRTI (n = 1). All patients experienced
an increase in the CD4 cell count, with the current median value of
574 cells/cmm (IQR, 403-739). The last median VL was 52 copies/mL
(IQR, 25-179). Notably, all our patients with a persistent LLV had less
than 500 copies/mL, although the median number of detectable VL
was 3 (IQR, 2-8).
Conclusions
Despite new regimens containing potent drugs, LLV remains a problem for HIV positive patients on ART. Clinicians need to closely monitor this category of patients while further studies will be required to
investigate the consequences of persistent LLV.
Page 4 of 29
O9
Infections in IDUs according to their HIV status
Adriana Hristea1,2, Irina Lăpădat1, Raluca Jipa1, Ruxandra Moroti1,2,
Șerban Benea1,2, Doina Antonică1, Irina Panait1, Roxana Petre3
1
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest,
Romania; 2Carol Davila University of Medicine and Pharmacy, Bucharest,
Romania; 3National Institute of Aerospace Medicine, Bucharest, Romania
Correspondence: Adriana Hristea (adriana_hristea@yahoo.com) –
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest,
Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O9
Background
The introduction of new psychoactive substances on the Romanian
market in 2008 was associated with high risk behavior for HIV acquisition compared to opioid abuse, which resulted in an increased
number of new HIV infections among injecting drug users (IDUs).
One hundred and forty nine (21 %) patients were IDUs out of a total
of 698 newly diagnosed with HIV infection in Romania, in 2015. Our
aim was to analyze the characteristics of IDUs according to their status for HIV infection.
Methods
We performed a retrospective descriptive study, analyzing the records of IDUs hospitalized between January and December 2015 in
our institution.
Results
We identified 93 IDUs, of which 79 (85 %) tested positive for HIV infection. Seventeen (22 %) HIV infected patients were diagnosed in
2015. There was an overall male predominance in both groups, 64
(81 %) in HIV infected patients and 12 (86 %) in HIV non-infected patients. Fifteen (19 %) HIV infected patients were on opioid substitution therapy versus 4 (29 %) HIV non-infected patients (p = 0.3, OR:
0.6, 95%CI: 0.2-2.1). The median age was similar in both groups, 31
(IQR: 26-35) in HIV infected patients versus 30 years (IQR: 25-33) in
HIV non-infected patients (p = 0.7). The median CD4 cell count was
92 (IQR: 12-340). Most of the patients (81 %) were in stage B and C
of HIV disease. Antiretroviral treatment (ART) coverage was of 37 %.
Median length of hospitalization was 13 days (IQR: 5-30) in HIV infected patients vs 7 days (IQR: 3-10) in HIV non-infected patients
(p = 0.1). Chronic hepatitis B was identified in 6 (8 %) HIV infected
vs 2 (14 %) HIV non-infected patients (p = 0.3, OR: 0.5, 95%CI: 0.092.7) and chronic hepatitis C in 66 (84 %) HIV infected vs 12 (86 %)
in HIV non-infected patients (p = 0.5, OR: 0.8, 95%CI: 0.2-4.2). The
main causes of hospitalization were: cellulitis in 27 (34 %) HIV infected vs 2 (14 %) HIV non-infected patients (p = 0.3, OR: 3.4,
95%CI: 0.2-46.4); pneumonia in 30 (38 %) HIV infected vs 4 (29 %)
HIV non-infected patients (p = 0.3, OR: 1.5, 95%CI: 0.4-5.3); tuberculosis in 21 (27 %) HIV infected vs 1(7 %) HIV non-infected patients
(p = 0.5, OR: 1.7, 95%CI: 0.1-20.7) and endocarditis in 9 (11 %) HIV
infected patients. Nine (11 %) HIV infected patients died during
hospitalization.
Conclusion
The majority of IDUs were young men, with HIV/HCV co-infection.
Most HIV infected IDUs were hospitalized in a late stage of HIV infection and had a longer duration of hospitalization. The ART coverage
in this population is very low. Cellulitis, pneumonia and tuberculosis
were more frequently seen in HIV-infected patients.
O10
Trends in combined antiretroviral therapy used in methadone
program integrated with HIV care - 20 years of experience
Justyna D. Kowalska1,2, Ewa Pietraszkiewicz1,2, Ewa Grycner1, Ewa FirlagBurkacka1, Andrzej Horban1,2
1
Hospital for Infectious Diseases, HIV Out-Patient Clinic, Warsaw, Poland;
2
Medical University of Warsaw, Department for Adult's Infectious
Diseases, Warsaw, Poland
Correspondence: Justyna D. Kowalska (jdkowalska@gmail.com) –
Hospital for Infectious Diseases, HIV Out-Patient Clinic, Warsaw, Poland
BMC Infectious Diseases 2016, 16(Suppl 3):O10
BMC Infectious Diseases 2016, Volume 16 Suppl 3
Background
In 1995 a methadone program was started at HIV clinic as integrated
services. The main purpose was to increase uptake, retention and adherence to cART among HIV-infected IDU in Central Poland. Here we
evaluate trends in antiretroviral therapy regimens used across
20 years of observation.
Methods
This is a retrospective analysis of observational database cohort of
cART naive, HIV-infected adults enrolled at registration to HIV care.
The cohort has been established with the purpose of prospective, active observation of HIV-positive patients routinely followed in HIV
Out-Patient Clinic, in the Hospital of Infectious Diseases in Warsaw.
Data are collected in real-time from the clinic database and include
demographic characteristics, history of clinical visits, cART history and
results of all tests performed in the clinic. In statistical analyses Chisquared and Kruskal-Wallis tests were used as appropriate for group
comparisons, all tests of significance were two-sided. Confidence
interval (CI) of 95 % was accepted. All analyses were performed using
SAS version 9.4 (SAS Institute, Cary, NC, USA).
Results
In total 267 (6.5 %) of 4062 patients registered in HIV Out-Patient
Clinic entered integrated methadone program (MET). There was a
significant difference between MET and non-MET groups in terms of
age at registration (median 35.2 [IQR: 30.3 - 41.2] vs. 33.27 [28.5
-40.0] years; p = 0.004), baseline lymphocyte CD4 count (440 [255 619] vs. 370 [211 - 531] cells/uL; p < 0.0001), nadir CD4 count (129
[49 - 217] vs. 242 [114 - 359]; p < 0.0001), baseline HIV RNA (4.16
[3.22 - 4.80] vs. 4.31 [3.39 - 4.93] log copies/mL; p = 0.012), most recent CD4 count (362 [207 - 560] vs. 503 [346 - 672]; p < 0.0001) and
most recent HIV RNA (1.69 [1.27 - 2.96] vs. 1.69 [1.27 - 1.97]; p =
0.006). In general MET participants had longer person-years of
follow-up (9.4 [6.0 - 12.7] vs. 4.8 [1.9 - 8.7]; p < 0.0001) and were longer on cART (7.6 [3.8 - 12.0] vs. 3.2 [1.0 - 7.0] years; p < 0.0001). Of all
MET patients 251 (94.0 %) started cART, 199 (79.3 %) with protease
inhibitor (PI) and 52 (20.7 %) with non-nucleoside reverse transcriptase inhibitor (NNRTI), p = 0.53. Among non-MET patients 3179
(83.3 %) started cART, 2227 (70.0 %) PI based, 853 (26.8 %) NNRTI
based, 68 (2.1 %) integrase inhibitor (INI) based and 31 (1.0 %) fusion
inhibitors based regimen, p < 0.0001 (for cART group comparison between MET and non-MET p = 0.003).
Conclusions
MET participants were more likely to start PI-containing cART, as
compared to non-MET patients. The utilization of INI is not yet an option used for MET patients. Data from clinical trials are showing no
drug-drug interactions between methadone and INI, thus encouraging to move this experience into clinical practice. Forming observational cohorts investigating the effects of this new drug group,
especially in respect to adverse drug reactions, seems to be rational
and valid approach.
O11
Extracellular cyclophilin A – inflammatory mediator in HIV infected
patients
Ovidiu Vlaicu1, Leontina Bănică1, Simona Paraschiv1, Ana-Maria Tudor2,
Ruxandra Moroti3, Dan Oțelea1
1
Molecular Diagnostic Laboratory, National Institute for Infectious
Diseases “Prof. Dr. Matei Balș”, Bucharest, Romania; 2Pediatric
Department, National Institute for Infectious Diseases “Prof. Dr. Matei
Balș”, Bucharest, Romania; 3Clinical Department III, National Institute for
Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest, Romania
Correspondence: Ovidiu Vlaicu (vlaicu.ovidiu@yahoo.com) – Molecular
Diagnostic Laboratory, National Institute for Infectious Diseases “Prof. Dr.
Matei Balș”, Bucharest, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O11
Background
Cyclophilin A (CypA) is known for its intracellular roles in protein folding, trafficking and T cell activation. However, a soluble form of CypA
was reported to be secreted as a result to inflammation. CypA
Page 5 of 29
proinflammatory potential was validated in some pathologic and
physiologic conditions (cardiovascular diseases, rheumatoid arthritis,
sepsis, cancer, ageing). Based on these facts we aimed to evaluate the
level of CypA and the soluble form of its receptor CD147 (sCD147) in
HIV infected patients and their association with inflammation.
Methods
Plasma samples from 29 HIV infected patients and 17 healthy controls (HC) were tested for levels of IL-6, C-reactive protein (CRP),
CypA, sCD147 by ELISA. Statistical evaluation of the data was performed with Man Whitney t test and Spearman correlation test, in
GraphPad Prism and p values < 0.05 were considered significant.
Results
HIV infected patients showed higher levels of inflammatory markers
(CRP and IL-6) as compared to HC, while CypA and sCD147 levels
were not significantly different. However, when HIV infected patients
were stratified according to viral loads (VL), those with detectable VL
had significantly higher levels of plasmatic CypA. As expected, HIV infected patients with detectable VL had significantly lower CD4 T cell
counts and CD4/CD8 ratios than those with undetectable VL. CypA
levels correlated negatively with CD4/CD8 ratios and positively with
VL; sCD147 was directly correlated with CD8 counts in HIV infected
patients.
Conclusion
HIV infection may induce CypA secretion with a positive feedback effect on inflammation.
Acknowledgment
This study was partly supported by UEFISCDI, Grant HIV-ID (260/2015) and
POSCCE Program, CRCBABI Project (642/2014).
O12
High cardiovascular disease risk in Serbian population, an issue of
concern
Bozana Dimitrijević1, Ivan Soldatović2, Đorđe Jevtović3, Jovana Kusić1,
Dubravka Salemović3, Jovan Ranin3, Gordana Dragović1
1
Department of Pharmacology, Clinical Pharmacology and Toxicology,
School of Medicine, University of Belgrade, Belgrade, Serbia; 2Institute for
Biomedical Statistics, School of Medicine, University of Belgrade,
Belgrade, Serbia; 3Infectious and Tropical Diseases Hospital, School of
Medicine, University of Belgrade, Belgrade, Serbia
Correspondence: Bozana Dimitrijević(drdimitrijevicb@gmail.com) –
Department of Pharmacology, Clinical Pharmacology and Toxicology,
School of Medicine, University of Belgrade, Belgrade, Serbia
BMC Infectious Diseases 2016, 16(Suppl 3):O12
Background
Cardiovascular disease (CVD) and coronary heart disease (CHD) have
become major causes of morbidity and mortality in HIV infected patients, due to the usage of combination antiretroviral therapy (cART)
as well as the pro-inflammatory effects of HIV infection, and traditional risk factors. In addition of this, Serbia is a country with one of
the highest rates of age-standardized mortality from CVD and CHD
within South Eastern Europe in general population, with almost no
primary prevention programmes on National level. Thus the aim of
this study was to estimate CVD and CHD risk scores in HIV infected
patients receiving cART in the HIV-treatment center in Belgrade
(HCB).
Methods
A cross-sectional analysis of 202 consecutive HIV infected patients
aged between 40 and 79 years who received antiretroviral therapy
for at least 6 months at the HCB. We estimated CVD and CHD risk
scores using Data Collection on Adverse Effects of Anti-HIV Drugs
study (DAD) model prevalence of cardiovascular risks in HIV-patients.
The study was approved by the Clinical Center of Serbia Ethics
Committee.
Results
There were 51 (25.2 %) females and 151 (74.8 %) males included in
the study. Clinical AIDS was observed in 89 (43.9 %) patients. The
median CD4+ T-cells count was 461 (IQR = 194-625) cells/mm3. The
BMC Infectious Diseases 2016, Volume 16 Suppl 3
prevalence of current smoking, hypertension and hypercholesterolemia (>6.2 mmol/L) were 100 (49.5 %), 64 (31.5 %) and 72 (35.4 %),
respectively. Fifty-one (25.2 %) persons were overweight, 15 (7.4 %)
were obese, 45 (22.3 %) had metabolic syndrome and diabetes 7
(3.5 %). Forty-three (21.3 %) persons were eligible for statin therapy
according to EACS (95 % confidence intervals [CI], 16.3 % to 27.4 %).
A high 5-year DAD CVD and CHD risk scores were 2.5 % (95 % CI
1.2 % - 6 %) and 2.1 % (95 % CI 1 % - 5.2 %), respectively. High 10year DAD CVD and CHD risk scores were 6.8 % (95 % CI 2.8 % 15.5 %) and 5.4 % (95 % CI 2.5 % - 13.5 %), respectively. While high
(>20 %) DAD CVD and DAD CHD risk scores were recorded in 35
(17.3 %) and 24 (11.8 %) patients, respectively.
Conclusion
We have demonstrated that almost one third of patient population included in this study has elevated CVD and CHD risk scores in accordance with the DAD model. Thus, intervention for reducing high risk and
preventive activities needs to be done in next coming period.
ORAL PRESENTATIONS
Session title: coinfections
O13
Genotypic rifampicin resistance in HIV/ tuberculosis coinfected
patients from a tertiary level infectious diseases hospital
Dragoș Florea1,2, Ioana Bădicuț1, Alexandru Rafila1,2, Cornel Camburu1,
Adriana Histrea1,2, Mihaela Frățilă1 and Dan Oțelea1
1
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest,
Romania; 2Carol Davila University of Medicine and Pharmacy, Bucharest,
Romania
Correspondence: Dragoș Florea (dflorea2002@yahoo.com) – National
Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O13
Background
Tuberculosis occurs frequently and has a major prognostic impact in
HIV patients. Rapid and reliable diagnostic methods for Mycobacterium tuberculosis infection are important both for adequate treatment
decisions and timely infection control procedures. The objective of
the present study was to analyze the rate of tuberculosis coinfection
and rifampicin resistance in HIV infected patients from a tertiary level
infectious diseases hospital in Romania.
Methods
Retrospective analysis of tuberculosis coinfection in HIV positive patients admitted in the National Institute for Infectious Diseases,
Bucharest, Romania from January 2014 to December 2015. The diagnosis of tuberculosis and rifampicin resistance was based on genotypic (MTB/RIF Xpert) and routine phenotypic methods (microscopy,
Lowenstein-Jensen cultivation).
Results
A number of 190 samples from HIV positive patients were received
over a two years period. Pulmonary samples were predominant, but
non-pulmonary samples were also collected: sputum (36.8 %), cerebrospinal fluid (30 %), bronchial aspirate (20.5 %), pleural effusion
(4.2 %), lymph node aspirate (3.1 %), broncho-alveolar lavage (2.6 %).
In 56 samples from 54 patients M. tuberculosis was detected using
genotypic and/or phenotypic methods. The positivity rate was 35 %
for pulmonary samples and 21 % for non-pulmonary samples. Genotypic rifampicin resistance was detected in 10 HIV infected patients
(18.5 %), most of them with pulmonary tuberculosis (7 cases).
Conclusions
Rifampicin resistance is detected in a high proportion of HIV/tuberculosis coinfected patients from a tertiary level infectious diseases
hospital. Genotypic methods able to provide a rapid diagnosis of
Page 6 of 29
tuberculosis infection and rifampicin resistance are needed in the
management of HIV patients.
Acknowledgments
This study was partly supported by POSCCE Program, CRCBABI Project
(642/2014).
O14
Occurrence of residual HCV RNA in liver and peripheral blood
mononuclear cells among patients with chronic hepatitis C
infection and/or HCV/HIV coinfection after IFN-based therapy
Ivana Gmizic1,2, Dubravka Salemovic1, Ivana Pesic-Pavlovic1, Marina Siljic2,
Valentina Nikolic2, Miljana Djonin-Nenezic1, Ivana Milosevic1, Branko
Brmbolic1, Maja Stanojevic2
1
Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia,
Belgrade, Serbia; 2Faculty of Medicine, University of Belgrade, Belgrade,
Serbia
Correspondence: Ivana Gmizic (gmizic_ivana@yahoo.com) – Clinic for
Infectious and Tropical Diseases, Clinical Centre of Serbia, Belgrade,
Serbia
BMC Infectious Diseases 2016, 16(Suppl 3):O14
Background
An entity of occult HCV infection has been described in various studies in past decade defining it as detectable HCV-RNA in the liver or
peripheral blood mononuclear cells (PBMCs) in the absence of detectable serum or plasma HCV-RNA. Still, the clinical significance of
these findings remains uncertain, in both treated and untreated patients. Treatment with pegylated interferon (IFN) plus ribavirin (RBV)
has long been standard of care for patients with chronic hepatitis C
virus (HCV) infection. Usually, liver biopsy was used a prerequisite for
starting therapy. Response to this therapy is known to depend on
the HCV genotype, with rates of sustained virological response (SVR)
in 40-50 % of genotype 1-infected and in about 70-80 % of genotype
2-infected individuals. This rate is lower in case of persisting HCV/HIV
co-infection.
Material/methods
The aim of this study was to investigate the occurrence of occult
HCV infection among patients with chronic HCV infection and/or
HCV/HIV coinfection after achieved SVR with IFN based therapy in
Serbia. We report preliminary results of this study. We examined the
presence of HCV RNA in liver tissue and PBMC in 47 patients who
underwent liver re-biopsy after successful treatment with combination peginterferon plus ribavirin, that yielded negative plasma
viremia. All patients were over 18 years old and consenting to participate in the study.
Results
Average age of included patients was 45 ± 13.6 (range 26-73),
whereas 29/47 patients were male (61.7 %). Pre-therapy genotyping
revealed genotype 1 as the most common one, with 57.4 % (n = 27/
47), followed by genotype 3 with 34 % (n = 16/47), genotype 2
and 4 in 4.3 % (n = 2/47). The most common risk was intravenous
drug use and surgical procedures (25.5 %). Average therapy duration was 37.4 weeks, whereas re-biopsy was performed on average 24.3 months post therapy completion (range 2-80 months).
There were 5 patients (10.6 %) with HCV/HIV coinfection, 4/5 were
male with average age 46 ± 14.8, with genotype 3 as predominant,
and 7.6 ± 8.2 months passed after therapy till re-biopsy performed.
Our preliminary findings demonstrated HCV RNA in 3/47 (6.38 %)
liver samples where 2/3 had pre-therapy genotype 3, including
one patient who had HCV/HIV coinfection.
Conclusions
Residual HCV RNA is present in 6.38 % in this study including one of
the patients, who has HIV as coinfection. Further studies are underway.
BMC Infectious Diseases 2016, Volume 16 Suppl 3
Acknowledgement
Funded as project 157024, by Ministry of Education, Science and
Technological development.
O15
Romanian nationwide screening for infection with HIV and
hepatitis B and C viruses
Anca Streinu-Cercel1,2, Oana Săndulescu1,2, Alina Cristina Neguț1,2,
Mioara Predescu2, Alexandra Mărdărescu3, Mihai Săndulescu1, Adrian
Streinu-Cercel1,2
1
Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;
2
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest,
Romania; 3Romanian HIV Center, Bucharest, Romania
Correspondence: Anca Streinu-Cercel (anca_sc@yahoo.com) – Carol
Davila University of Medicine and Pharmacy, Bucharest, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O15
Introduction
Despite the introduction of national immunization against HBV since
1996 through neonatal vaccination and catch-up regimens, hepatitis
B remains prevalent and underdiagnosed in Romania in 2016. Hepatitis C and HIV infection also remain important public health concerns and require the implementation of nationwide screening
studies to ascertain real-life incidences and the extent to which they
are underdiagnosed.
Methods
We have implemented a study to screen for hepatitis B and C viruses
(HBV, HCV) and HIV infection in the general population in Romania.
Patients were referred to the National Institute for Infectious Diseases
“Prof. Dr. Matei Balș” from the general practitioner (GP). The GPs
were previously trained by infectious diseases specialists and received support during the program. All subjects voluntarily signed a
study-specific informed consent form and filled out a questionnaire
assessing risk factors for transmission of HBV, HCV and HIV. We
present the results of the first 9937 patients screened in this study
from May to August 2015.
Results
The tested population was made up of 36 % males and 64 % females, with a mean age of 48 years old ± 29 years. Out of the total
number of 9937 persons tested, 540 were found positive for HBsAg
(5.4 %), 267 for anti-HCV (2.7 %), and 11 (0.1 %) had positive ELISA
tests for HIV infection. However, viral loads for HBV DNA, HCV RNA
and HIV RNA were negative in 230 (42.6 %), 104 (39.0 %) and 2
(18.2 %) cases, respectively. The Romani population group had
good addressability to general practitioners and to the screening
study. Notably, the incidence of HBV, HCV and HIV infection was
lower in the Romani group than in the rest of the patients: 2/186
(1.1 %) HBV, 1/186 (0.5 %) HCV, 0/186 (0 %) HIV infection vs. 308/
9751 (3.2 %) HBV, 162/9751 (1.7 %) HCV and 9/9751 (0.1 %) HIV
infection.
Conclusion
The preliminary results of the study characterized the relative incidence of HBV, HCV and HIV infection in Romania. The study
group was representative, and the age distribution was normal,
suggesting that the data are valid for the general population in
Romania, although specific high-risk groups still need to be defined. The relative incidences of HIV and hepatitis B and C in this
study were fairly low, and the Romani population had lower incidences compared with the rest of the group, suggesting that
these viral infections may still be underdiagnosed in the general
population.
Page 7 of 29
O16
Treatment emergent variants to combined direct antiviral agents
therapy against hepatitis C virus
Ana Belen Pérez1, Natalia Chueca1, Marta Álvarez1, Juan Carlos Alados2,
Antonio Rivero3, Francisco Vera4, Marcial Delgado5, Javier Salmeron6,
Miguel Jiménez7, Maria José Blanco8, Moises Diago9, Miguel Garciadeltoro10, Francisco Téllez11, Federico García1
1
Servicio de Microbiologia. CHUG, Hospital San Cecilio, Instituto de
investigacion IBS, Granada, Spain; 2Servicio de Microbiologia. Hospital de
Jerez de la Frontera, Cádiz, Spain; 3Servicio de Enfermedades Infecciosas,
Hospital Reina Sofia, Cordoba, Spain; 4Servicio de Enfermedades
Infecciosas, Hospital Santa Lucia, Cartagena, Spain; 5Servicio de
Enfermedades Infecciosas, Hospital Regional Carlos Haya, Malaga, Spain;
6
UGC Digestivo, HUSC, Granada, Spain; 7UGC Digestivo, Hospital
Regional Carlos Haya, Malaga, Spain; 8UGC Enfermedades Digestivas,
Hospital de Jerez de la Frontera, Cádiz, Spain; 9Servicio de Ap. Digestivo,
H General de Valencia, Valencia, Spain; 10Unidad de Enfermedades
Infecciosas, H General de Valencia, Valencia, Spain; 11Servicio de
Medicina Interna, Hospital de la Linea, Cadiz, Spain
Correspondence: Federico García (fegarcia@ugr.es) – Servicio de
Microbiologia. CHUG, Hospital San Cecilio, Instituto de investigacion IBS,
Granada, Spain
BMC Infectious Diseases 2016, 16(Suppl 3):O16
Background
Treatment emergent variants (TEVs) to first line direct antiviral agents
against HCV may represent a problem of major concern. The information on real life setting is scarce and may vary from that of clinical
trials. AASLD now recommend testing for Q80K and NS5a RAVs in patients that, having failed first line regimens, have cirrhosis and/or are
in need of urgent retreatment. Here we describe the first data of
TEVs in a real life setting in Spain.
Patients & Methods
We conducted an observational study, including all patients referred to our Reference Center for antiviral resistance from
across Spain, from July to November 2015. TEVs were investigated using population sequencing on the failing sample, and in
parallel stored baseline samples, when available. Genotype specific primers were used for NS5a (codons 1-99; positions 28, 29,
30, 31, 32, 58, 62, 92 & 93) and NS3 sequencing (codons 1-181;
positions 36, 43, 55, 56, 80, 122, 155, 156, 168 & 170). Pangenotypic primers were used for NS5b sequencing, which was also
used for re-genotyping.
Results
31 patients failing an interferon free DAA combination were included. Most of them were male (86.2 %) with a median age of
53 (IQR 50-61), and a median HCV viral load of 6.22 logs (IQR
5.64-6.49). 8 patients were HCV GT1a, 14 GT1b, 5 GT 3a and 4
GT4d. 15 patients had failed to Sofosbuvir-Simeprevir based
regimens, and 16 to a Sofosbuvir-NS5a inhibitor combination
(Daclatasvir or Ledipasvir). We did not observe any Sofosbuvir
TEV. TEVs were observed in 9 of the 15 patients failing Simeprevir based regimens (60.0 %), including S122T, n = 1; D168H, n = 1;
D168V, n = 4; V36D + D168V, n = 1; Q80K + R155K, n = 1; Q80K +
A156S, n = 1. For patients on an NS5A inhibitor based regimen,
TEVs were found for 14 out of 16 patients (87.5 %), including
Q30H, n = 2; Q30K, n = 1; Q30R, n = 1; L31M, n = 1; Y93H, n = 4;
L31M + Y93H, n = 2; L31V + Y93H, n = 2; T28A + Q30R, n = 1. NS5b,
NS3 & NS5A sequencing, reclassified two patients initially genotyped as GT1b as GT1a. Reinfection was confirmed using massive
parallel sequencing and phylogenetic analysis on baseline (GT1a)
and relapse samples (GT3a).
BMC Infectious Diseases 2016, Volume 16 Suppl 3
Conclusions
We present the first results on the genetic barrier and TEV characterization of patients that relapse to Sofosbuvir based regimens in
Spain. The high genetic barrier to Sofosbuvir was confirmed, as well
as a high prevalence of NS5a associated TEVs. We have also shown
the ability of resistance assays to detect errors in genotyping by
commercial genotyping assays, as well as to document reinfection rather than relapse.
O17
Clinical and epidemiological aspects in tuberculosis/HIV coinfected
patients
Diana Tănase, Eliza Manea, Rodica Bacruban, Dragoș Florea, Dan Oțelea,
Alexandru Rafila, Mariana Mărdărescu, Adriana Hristea
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest,
Romania
Correspondence: Diana Tănase (dianapetrache07@yahoo.com) –
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest,
Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O17
Page 8 of 29
O18
Resistance to NS3 protease inhibitors in persons with chronic
hepatitis C infected with hepatitis C virus subtype 1a from Croatia
Ivana Grgic1, Ana Planinic1, Maja Santak3, Lana Gorenec1, Snjezana
Zidovec Lepej1, Adriana Vince2
1
Department for Molecular Diagnostic And Flow Cytometry, University
Hospital for Infectious Diseases Zagreb, Zagreb, Croatia; 2Department of
Viral Hepatitis, University Hospital for Infectious Diseases Zagreb, Zagreb,
Croatia; 3Centre for Research and Knowledge Transfer in Biotechnology,
Laboratory for Molecular Biomedicine, University of Zagreb, Zagreb,
Croatia
Correspondence: Ivana Grgic (ivanahobby@gmail.com) – Department
for Molecular Diagnostic And Flow Cytometry, University Hospital for
Infectious Diseases Zagreb, Zagreb, Croatia
BMC Infectious Diseases 2016, 16(Suppl 3):O18
Background
An NS3 inhibitor simeprevir is one of the treatment options for
chronic hepatitis C in Croatia (in combination with pegylated interferon alpha and ribavirin). Mutation Q80K in persons infected with
HCV subtype 1a is associated with reduced treatment response to
simeprevir. The aim of this study was to analyze the frequency of
Q80K mutations in persons with HCV subtype 1a infection prior to
treatment with direct acting antivirals and to analyze other mutations
associated with HCV resistance to NS3 inhibitors.
Methods
The study included 85 persons with chronic hepatitis C infected with
HCV subtype 1a receiving clinical care at the Department of Viral
Hepatitis of the University Hospital for Infectious Diseases, Zagreb
and Croatian Reference Center for Viral Hepatitis. HCV subtype was
determined by using Inno LiPA genotyping test. Detection of Q80K
and other mutations associated with resistance to NS3 inhibitors was
performed as a part of pre-treatment diagnostic workup by
population-based sequencing on ABI PRISM - 3100 Genetic Analyzer.
Geno2Pheno algorithm was used for the interpretation of resistance
analysis results.
Results
Resistance to Simeprevir was detected in 36 of 85 (42 %) of patients.
Subtype 1a clade I was detected in 41 patients and clade II in 44 patients. Mutation Q80K was detected only in patients infected with
HCV subtype 1a clade I (32 of 41 patients). The majority of patients
with clade I (n = 21) were infected with strains carrying Q80K mutation only whereas 11 patients carried a combination of Q80K and
other mutations associated with NS3 resistance mutations. Mutations
associated with resistance to NS3 inhibitors excluding Q80K were detected in 4 of 44 patients infected with subtype 1a clade II. The patterns of resistance mutations included: 155 T and 170 V (n = 1
patient), 36 L, 155 K and 170 V (n = 1), 138A, 155S, 168G, 170C and
43S (n = 1) and 36 L (n = 1, possible resistance).
Conclusion
The results of this study have shown a high prevalence of Q80K in
patients with chronic hepatitis C infected with clade I subtype 1a
from Croatia. The contribution of other mutations to NS3 inhibitors
resistance was limited.
Background
In Romania HIV and tuberculosis (TB) epidemics are independent and
most of the TB patients are not infected with HIV. Nevertheless, the
increasing prevalence of HIV infection, especially in high-risk populations like intravenous drug users (IDUs), may also contribute to an increased number of TB co-infected patients. In Romania, 113 of the
698 new HIV patients, were co-infected with TB in 2015.
Objective
The aim of this study was to describe the demographic, clinical profile and the HIV status of the patients diagnosed with TB in a tertiary
infectious disease hospital.
Methods
We studied retrospectively adults with suspected or confirmed TB, hospitalized in our institution between January and December 2015. We
collected demographic, clinical and laboratory data. TB confirmation
was based on routine microbiological methods and/or GeneXPERT.
Results
Out of 114 studied patients 63 (55.3 %) were HIV-positive, 40
(35.1 %) HIV negative and 11 (9.6 %) with status unknown. Male patients were predominant in both groups: 68.3 % in HIV infected and
57.5 % in HIV non-infected group, respectively (p = 0.1). The median
age was 32 (IQR 27-39) in HIV-positive patients compared with 39
(IQR 28-62) in HIV-negative patients (p < 0.01). A quarter (23.8 %) of
the 63 TB/HIV co-infected patients were IDUs. Thirteen (20.6 %) TB/
HIV co-infected patients were newly diagnosed with HIV and were
very late presenters, with a median CD4 of 33 cells/cmm (IQR 16108). There was no significant difference between the HIV-positive
and HIV negative group regarding TB localization. Pulmonary TB
(PTB) was found in 54 % versus 50 %, extra-pulmonary TB (EPTB) in
27 % versus 38 % and PTB associated with EPTB were found 19 %
versus 12 % of cases. TB was confirmed in 47 (74.6 %) HIV infected
patients versus 23 (57.5 %) non-infected patients. Microbiologically
confirmed TB (smear/culture) was seen in 26 (55.3 %) versus 10
(43.4 %) in HIV-infected versus HIV non-infected respectively (p =
0.06). TB was confirmed by PCR in 61 samples, 40 (63.5 %) in HIV infected and 21 (52.5 %) in HIV non-infected patients (p = 0.1). Ten
(16.4 %) samples were resistant to rifampicin, 8 (80 %) of them isolated from HIV-infected patients. A short duration from admission to
a positive diagnosis of TB (5.2 days) was obtained for both groups.
Conclusion
More than half of newly diagnosed TB patients were HIV-coinfected.
HIV/TB patients were younger, but there was no difference between
the two groups regarding the TB localization. We noticed a similar
proportion of EPTB regardless of HIV status. We found a high rate of
rifampicin resistance mainly in HIV-infected patients.
O19
Analysis of a simplified diagnostic score for tuberculous meningitis
in HIV-infected adults with meningitis
Eliza Manea1, Adriana Hristea1,2, Șerban Benea1,2, Ruxandra Moroti1,2,
Diana Tănase1, Cristian M. Niculae1, Simona Merisor1, Raluca Jipa1
1
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest,
Romania; 2Carol Davila University of Medicine and Pharmacy, Bucharest,
Romania
Correspondence: Eliza Manea (elizamanea10@yahoo.com) – National
Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O19
Acknowledgments
This study was partly supported by POSCCE Program, CRCBABI Project
(642/2014).
Background
Tuberculous meningitis (TBM) and cryptococcal meningitis (CM) are
the main causes of meningitis in HIV infected adults. A simplified
BMC Infectious Diseases 2016, Volume 16 Suppl 3
diagnostic score (SDS) based on four variables was created as a prediction rule to differentiate patients with TBM from those with viral
meningitis. (Hristea et al Int J Tuberc Lung Dis, 2012) The four variables were: duration of symptoms before admission of ≥5 days, presence of neurological impairment (altered consciousness, seizures,
mild focal signs, multiple cranial nerve palsies, dense hemiplegia or
paraparesis), CSF/blood glucose ratio <0.5 and CSF protein level >
100 mg/dL).We examined if the SDS would correctly identify TBM vs
CM in HIV-infected patients.
Methods
Retrospective study of HIV-infected patients hospitalized between
January 2012-December 2015 for TBM or CM. Patients were classified
according to the consensus definition and scoring system published
by Marais into three categories: definite (positive CSF culture for M.
tuberculosis and/or positive commercial nucleic acid amplification
test), probable and possible. CM diagnosis was established upon
positive India ink stain, culture and/or cryptococcal antigen assay.
Results
We identified 17 patients with TBM and 18 patients with CM. Out of
the 17 TBM patients 13 (77 %) had definite, 3 (17 %) probable and 1
(6 %) possible TBM. All patients with TBM had a duration of symptoms before admission of ≥5 days; presence of neurological impairment in 11(65 %); CSF/blood glucose ratio <0.5 in 15 (88 %); CSF
protein level >100 mg/dL in 13 (76 %). The SDS correctly identified
16 (94 %) cases (including all cases of microbiologically documented
TBM). In patients with CM, 12 (67 %) patients had a duration of
symptoms before admission of ≥5 days, 14 (78 %) patients had
neurological impairment, 13 (72 %) patients had CSF /blood glucose
ratio <0.5 and 6 (33 %) patients had CSF protein level >100 mg/dL.
The SDS would have labeled 13 (72 %) patients with CM as TBM.
The SDS sensitivity was 94.1 (95CI 71.3-99.8) and the specificity 27,8
(95CI 9.7-53.5) in differentiating TBM vs CM.
Conclusions
In HIV-infected patients the SDS does not satisfactorily differentiate
between the two causes of chronic meningitis, TBM and CM.
Acknowledgments
This study was partly supported by POSCCE Program, CRCBABI Project
(642/2014).
ORAL PRESENTATIONS
Session: resistance, tropism, laboratory monitoring
O20
Molecular tracing of the origin of HIV-1 infection among persons
who inject drugs in Athens: a phyloethnic study
Dimitrios Paraskevis1, Evangelia Kostaki1, Georgios K. Nikolopoulos2,
Vana Sypsa1, Mina Psichogiou3, Dimitra Paraskeva3, Athanassios
Skoutelis4, Meni Malliori5, Samuel R. Friedman6, Angelos Hatzakis1
1
Department of Hygiene, Epidemiology and Medical Statistics, Medical
School, University of Athens, Athens, Greece; 2Hellenic Center for
Disease Control and Prevention, Amarousio, Greece; 3Laikon General
Hospital, Department of Propedeutic Medicine, Athens, Greece; 4Fifth
Department of Internal Medicine and Infectious Diseases, Evangelismos
Hospital Athens, Athens, Greece; 5Medical School, University of Athens,
Athens, Greece; 6National Development and Research Institutes (NDRI),
New York, USA
Correspondence: Dimitrios Paraskevis (dparask@med.uoa.gr) –
Department of Hygiene, Epidemiology and Medical Statistics, Medical
School, University of Athens, Athens, Greece
BMC Infectious Diseases 2016, 16(Suppl 3):O20
Background
High numbers of HIV-1 infections among people who inject drugs
(PWIDs) have been diagnosed in Athens, Greece since 2011. We
aimed to trace the geographic origin of HIV-1 infection for migrant
PWIDs and to investigate if transmissions occur more frequently
among individuals with a non-Greek origin versus those between migrants and Greeks.
Page 9 of 29
Methods
Our sample included 2,977 HIV-1 infected individuals diagnosed in
Southern Greece between 1/1/2011-31/10/2014. Phylogenetic analyses used maximum likelihood method. The hypothesis of ethnic
compartmentalization was tested by reconstructing ancestral states
of characters at the tips using the criterion of parsimony over a set
of bootstrap trees (statistical phyloethnic study).
Results
In our sample, 29.4 % (N = 874) were PWIDs. Phylogenetic analyses
showed the existence of four major PWID-local transmission networks (LTNs): CRF14_BG (456, 58.3 %), CRF35_AD (149, 19.1 %), subtype B (118, 15.1 %), and subtype A (59, 7.5 %). The target
population was 190 individuals (184 non-Greek PWIDs and 6 nonPWID migrants) who had been infected within the PWID-LTNs. 150
(78.9 %) of our target population belonged to LTNs and therefore
the origin of their infection was assumed to be in Greece. Similarly,
24 persons (12.6 %) with recombinants with at least one subtype
identified in LTNs were probably infected in Greece. The putative origin of infection for 16 unclustered sequences was in: Greece (subtypes A, B, CRF01_AE; N = 7; 3.7 %), Romania (subtype F, CRF14_BG;
N = 2; 1.1 %), Turkey and Bulgaria (URF A/U; N = 1; 0.5 %), Greece or
Israel (CRF03_AB; N = 1; 0.5 %), Turkey (unclassified sequences, N = 4;
2.1 %), and a non-Greek region (unclassified; N = 1; 0.5 %). Statistical
phyloethnic analysis provided evidence for significant ethnic
compartmentalization for subtype A and CRF14_BG.
Conclusion
Our analysis showed that the majority (95.3 %) of infections among
migrants (PWIDs and non-PWIDs) clustered within PWID-LTNs originated in Greece. Our findings suggest that across different ethnic
groups, HIV infections are more likely to have been locally acquired.
This is a novel finding and contrasts with patterns of HIV spread
among migrants (non-B subepidemic) in Europe. We also showed the
existence of significant transmission networking between migrants.
These findings could have public health implications, especially in
PWID-related epidemics.
Funding
US National Institute on Drug Abuse (NIDA) (Grant: DP1 DA034989
and Hellenic Scientific Society for the Study of AIDS and STDs).
Acknowledgements
The study was implemented under NSRF 2007-2013 and cofounded by
European Social Fund and national resources. Additional financial support
was provided by the Hellenic Scientific Society for the Study of AIDS and
STDs and the grant “Preventing HIV Transmission by Recently-Infected Drug
Users” project (NIH National Institute of Drug Abuse grant DP1 DA034989).
O21
The dynamics of virological response to HIV-1 infection and
antiretroviral therapy initiation in patients with and without
HLA-B*5701 Allele
Malgorzata Hackiewicz1, Piotr Zabek2, Ewa Firlag-Burkacka2,
Andrzej Horban1,2, Justyna Dominika Kowalska1,2
1
Department for Adults Infectious Diseases, Medical University of
Warsaw, Warsaw, Poland; 2HIV Out-Patient Clinic, Hospital for Infectious
Diseases, Warsaw, Poland
Correspondence: Malgorzata Hackiewicz
(hackiewiczmalgorzata@gmail.com) – Department for Adults Infectious
Diseases, Medical University of Warsaw, Warsaw, Poland
BMC Infectious Diseases 2016, 16(Suppl 3):O21
Background
HLA-B*5701 is linked to better control of HIV-1 replication. We investigate the dynamics in HIV replication and suppression in relation to
HLA-B*5701 and antiretroviral therapy (ART).
Methods
HIV Out-Patient Clinic database collects information on laboratory
values and medical visits since 1994. Patients with available HLAB*5701 test and >3 HIV RNA measurements (or 3 before starting
ART) were eligible for analyses. HLA-B*5701 allele was determined
BMC Infectious Diseases 2016, Volume 16 Suppl 3
by PCR-SSP (Inno-Train HLA-B Ready Gene B57 PCR-SSP). Nonparametric tests were used for group comparison and KaplanMeier survival analyses to estimate the probability of achieving
HIV RNA <50 copies/ml.
Results
In total 440 patients were included and 31 (7 %) were HLAB*5701(+). 341 (77.5 %) patients started ART, 95.3 % achieved HIV
RNA < 50. Baseline, second and third HIV RNA values were lower in
the HLA-B*5701 positive. Baseline median values were 3.6 vs 4.16 log
copies/ml; p = 0.008, second HIV RNA median values were 3.45 vs
4.11 log copies/ml, and third median values were 3.82 vs 4.21 log
copies/ml. CD4 baseline count was not statistically significant in the
compared groups (553 cells/ul HLA-B*5701 positive, and 509 cells/ul
HLA-B*5701 negative p = 0.08). Median time to starting ART did not
differ significantly between HLA(+) and (-) group (2.83 and 2.34 years;
p = 0.16), but median time to achieving HIV RNA <50 did (0.14 and
0.34 years; p = 0.008). Median parameters showing HIV positive patients' general condition, like hemoglobin and CRP were the same in
both groups. Median hemoglobin was 14.8 mg% (p = 0.81) in both
HLA-B*5701 positive and negative. Median CRP was 5 mg/l in both
HLA-B*5701 (+) and (-) (p = 0.02). Median D-dimers did not differ significantly between two groups (236 ug/l HLA-B*5701 (+) and 220 ug/
l HLA-B*5701 (-) p = 0.91).
Conclusions
We present that patients with HLA-B*5701(+) have both lower viral
set point before starting treatment and shorter time to achieving undetectable HIV RNA after starting ART. HLA-B*5701 may play an additive role to HIV suppression in patients starting ARV.
O22
Increase in the numbers of non-B subtypes and potential
recombinant forms circulating among Slovenian MSM in the recent
years
Maja M. Lunar1, Jana Mlakar1, Mario Poljak1
1
Institute of Microbiology and Immunology, Faculty of Medicine,
University of Ljubljana, Ljubljana, Slovenia
Correspondence: Maja M. Lunar (maja.lunar@mf.uni-lj.si) – Institute of
Microbiology and Immunology, Faculty of Medicine, University of
Ljubljana, Ljubljana, Slovenia
BMC Infectious Diseases 2016, 16(Suppl 3):O22
Background
In Slovenia as in many Western countries subtype B is still a predominant subtype and was historically correlated with the epidemic among
men who have sex with men (MSM). In the recent years, several reports
demonstrating an increasing prevalence of non-B subtypes have been
published. The majority of infections with non-B subtypes were linked
with the heterosexual mode of transmission in previous Slovenian studies, thus the aim of this study was to investigate whether non-B subtypes are becoming more prevalent also among MSM in Slovenia.
Methods
Between the years 2000-2014 a total of 520 persons were diagnosed
with HIV-1 infection in Slovenia. Under the study of HIV-1 transmitted
drug resistance filled questionnaires were obtained for 440 patients
and amongst 326 patients reported homosexual contact as the most
probable mode of HIV acquisition. Subsequently, partial pol sequences were obtained for 252 MSM patients which were included
in the present study. Sequences were analyzed using the following
automatic subtyping tools: REGA 2.0, REGA 3.0, COMET HIV-1 1.0,
jpHMM and SCUEAL. Sequences that gave divergent subtyping results were considered to be potential recombinant forms. Temporal
trend of the proportion of non-B and potential recombinant sequences (both combined termed as “non-pure subtype B” sequences)
was evaluated with Fisher exact test used for the assessment of statistical significance.
Results
All five subtyping tools gave concordant subtyping results to 230/
252 (91.3 %) of sequences. Pure subtype B was assigned to 226/252
(89.7 %) sequences and subtype A, subtype C, subtype F and CRF01_AE
Page 10 of 29
were determined in one patient each (0.4 %). The remaining 22/252
(8.7 %) sequences yielded divergent results with at least one of the
subtyping tools, an indication to a possible recombination event in
the past. An increase in the proportion of “non-pure subtype B”
HIV-1 variants was noted over the years with 0 % (95 % confidence
interval (CI): 0-16 %), 5 % (95 % CI: 1-15 %), 4 % (95 % CI: 0-13 %),
11 % (95 % CI: 4-21 %) and 25 % (95 % CI: 15-39 %) determined in
the years 2000-2002, 2003-2005, 2006-2008, 2009-2011 and 20122014, respectively. The marked increase was on account of an increasing number of potential recombinant sequences with subtype
B as one of the founder subtypes, since this subtype was identified
in 21/22 of divergent sequences. The remaining divergent sequence was a complex recombinant containing subtypes D and G.
Additionally, all 4 pure non-B subtyped sequences were determined
in patients diagnosed in the last two years (2013-2014). The obtained results indicate that subtypes other than B are entering the
HIV-1 MSM epidemic in Slovenia, making recombination events
among different subtypes more plausible.
Conclusion
A marked increase in the numbers of non-B subtypes and potential
recombinant forms was observed among MSM in Slovenia in the recent years. This finding indicates that subtypes other than B are entering the MSM epidemic in our region bearing diagnostic and
clinical significance.
O23
Genotyping intrahost polymorphisms in hepatitis C virus E2
protein associated with resistance to antibody neutralization
Leontina Bănică1, Eliza Martin2, Valeriu Gheorghiță3, Andrei Petrescu2,
Dan Oțelea1, Costin-Ioan Popescu2, Simona Paraschiv1
1
Molecular Diagnostic Laboratory, National Institute for Infectious
Diseases “Prof. Dr. Matei Balș”, Bucharest, Romania; 2Institute of
Biochemistry of the Romanian Academy, Bucharest, Romania; 3Clinical
Department, National Institute for Infectious Diseases “Prof. Dr. Matei
Balș”, Bucharest, Romania
Correspondence: Leontina Bănică (leo_mirela@yahoo.com) – Molecular
Diagnostic Laboratory, National Institute for Infectious Diseases
“Prof. Dr. Matei Balș”, Bucharest, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O23
Background
Hepatitis C virus (HCV) represents a serious global health problem
with 170 million people infected worldwide. Despite the major advance in the HCV standard of care there is need of a vaccine for both
prophylactic and therapeutic purposes. The major challenge in vaccine development is represented by the genetic diversity of the HCV
envelope protein which may be overcome by a proper cellular and
humoral immune response. In chronic infection the antibodies generated are unable to neutralize the virus due to multiple immune evasion
mechanisms
among
which
neutralizing
resistance
polymorphisms. Herein, we present a method to evaluate intrahost
variability in HCV E1E2 region and to identify polymorphisms possibly associated with resistance to antibody neutralization.
Methods
Blood samples from two HCV genotype 1b infected patients with different stages of fibrosis were collected. Viral RNA was extracted from
patient sera and following reverse transcription, the E1E2 region of
HCV genome was specifically amplified in 2 rounds PCR reaction. The
amplicon was cloned in the mammalian expression vector
pcDNA3.1/V5-His TOPO TA following the manufacturer instructions.
For each clone, the E1E2 region was sequenced using 6 different
primers and 3500 ABI instrument. Seqscape software was used to assemble and generate the consensus sequences for each clone and
BioEdit and FastTree softwares were further used to analyse the genetic evolution and the intra and interhost viral diversity. Structural
modeling and sequence analysis bioinformatic techniques were used
to select E1E2 envelopes for further analysis. The functionality and
the sensitivity to neutralization of the selected HCV envelopes were
evaluated using the HCV pseudotyping system.
BMC Infectious Diseases 2016, Volume 16 Suppl 3
Results
Ten complete ORFs of HCV E1E2 envelope glycoproteins for each patient were cloned. High intra-host variability was observed for both
patients, one of them (F1 fibrosis stage patient) presenting two distinct viral sub-populations, as indicated by the phylogenetic analysis.
Further, we have focused on aminoacid positions previously reported
to be involved in resistance to antibody neutralization. The residues
were mapped on a 3D structural model of E2 glycoprotein based on
the crystal structure of the core domain of HCV E2. Relying on the
bioinformatic analysis, we selected variants which are likely to be resistant to antibody neutralization. Further, we tested the functionality and
sensitivity to neutralization of the HCV E1E2 envelopes. We are discussing possible mechanisms of resistance to antibody neutralization.
Conclusions
Mapping the intrahost diversity of HCV E1E2 glycoproteins will contribute to the understanding of the molecular mechanism governing
resistance to neutralizing antibodies and vaccine design.
Acknowledgments
This study was supported by ANCSI grant EEA-JRP-RO-NO-2013-1-0022, Grant
GreenVac and by POSCCE Program, CRCBABI Project (642/2014).
O24
Genotyping of HCV NS3 protease inhibitors resistance and
phenotyping of rare double resistance mutations in HCV cell
culture system
Emil Neaga1, Vlaicu Ovidiu1, Andrei Juncu2, Leontina Bănică1, Simona
Paraschiv1, Dan Oțelea1, Costin-Ioan Popescu2
1
National Institute for Infectious Disease “Prof. Dr. Matei Balș”, Bucharest,
Romania; 2Institute of Biochemistry of the Romanian Academy,
Bucharest, Romania
Correspondence: Costin-Ioan Popescu (pop@biochim.ro) – National
Institute for Infectious Disease “Prof. Dr. Matei Balș”, Bucharest, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O24
Background
For human immunodeficiency virus (HIV) infected patients, the hepatitis
C virus (HCV) co-infection represents a serious problem because HIVHCV co-infection represents the major cause of liver related morbidity
among this group. Recently, the HCV standard of care was profoundly
upgraded with direct acting antivirals (DAA) which are administrated
alone or in combination with pegylated interferon alpha and ribavirin.
Although the efficacy of the new therapies is quite high, drug resistance and viral genetic diversity are still issues to be investigated.
Methods
For our study, we selected sera from genotype 1b patients who
failed to achieve sustained virological response (SVR) after treatment
with triple therapy consisting of first or second generation HCV NS3
protease inhibitors (PI), alpha interferon and ribavirin. The resistance
was genotyped by population sequencing in the HCV NS3 serine protease region. To phenotype the resistance, we used two recombinant
viruses: genotype 1a TNcc cell culture adapted virus and 5’UTRNS5A1a/2a chimeric virus. The replication and secretion capacity were
evaluated by anti-HCV core ELISA assay and infectivity was assessed
by titration using the foci forming unit assay.
Results
Interestingly, we found a rare combination of double lower level resistance mutations (T54S, R155K, A156S) associated with elevated viral
loads suggesting a minimal effect on the viral fitness. We are discussing
possible compensation mechanisms between HCV NS3 PI resistance
mutations.
Conclusion
Phenotyping of drug resistance in clinical relevant cell culture systems will contribute to our understanding of drug resistance mechanisms in the emerging interferon-free HCV therapy era.
Acknowledgments
The project was supported by Grant POSDRU/1591/1.5/S/135760-CERO and
by POSCCE Program, CRCBABI Project (642/2014).
Page 11 of 29
ORAL PRESENTATIONS
Session: NeuroHIV
O25
Employment status controls the relationship between
neurocognitive impairment and depression in a cohort of young
HIV-infected adults since childhood
Adrian Luca1, Florin Lazăr2, Anca Elena Luca3, Luminița Ene3,
Cristian Achim4
1
Faculty of Psychology and Education Sciences, University of Bucharest,
Bucharest, Romania; 2Faculty of Sociology and Social Work, University of
Bucharest, Bucharest, Romania; 3“Dr. Victor Babeș” Hospital for Infectious
and Tropical Diseases, Bucharest, Romania; 4HIV Neurobehavioral
Research Center, University of California, San Diego, USA
Correspondence: Adrian Luca (adrianluca@gmail.com) – Faculty of
Psychology and Education Sciences, University of Bucharest, Bucharest,
Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O25
Background
Children with parenterally acquired HIV infection in childhood in the
early ’90, living with chronic HIV for over 25 years might have HIVassociated neurocognitive impairment (NCI). Moreover they face
challenges regarding everyday functionality, depression, social interactions and low employment that we aimed to investigate in relationship with their NCI.
Methods
A clinic-based survey among 233 HIV+ participants with a median
age of 24.3 years, 47.6 % males infected since childhood was carried
out between 2012-2015 in an infectious diseases hospital in
Bucharest, Romania. Patients’ functioning was assessed using two
self-report questionnaires that report level of competence in performing instrumental and basic tasks of everyday life (Activities of
Daily Living (ADL) (α = 0.67)) and subjective cognitive complaints
(Patient’s Assessment of Own Functioning Inventory (PAOFI) (α =
0.93)), NCI was investigated with a neurocognitive battery assessing 7 domains known to be most affected by HIV with a composite global deficit score (GDS). Other measures included: Beck
Depression Inventory II (BDI) (α = 0.89), a performance-based skills
assessment (UPSA, α = 0.65) together with data on their job status,
and social interactions (number of daily interactions outside family). The present analysis is focusing on the association between
depression and NCI.
Results
Depression is positively associated with impairment (GDS) (sig. = 0.026),
daily living dysfunctionalities (ADL) (sig. = 0.000), more cognitive psychological complaints (PAOFI) (sig. = 0.000) and fewer social interactions
(sig. = 0.006). Moreover, having a job controls the relationship between
depression and cognitive functioning (GDS), zero-order correlation (r =
0.145, sig. = 0.026) and correlation with control for employment status
is r = 0.119, sig = 0.070. Unemployed depressive persons demonstrate a
cognitive deficit (mGDS = 0.63, F = 2.899, sig. = 0.036, η2 = 0.037), a decline in daily functioning (mADL = 4.44, F = 9.329, sig. = 0.000, η2 =
0.109), more cognitive complaints (mPAOFI = 5.19, F = 18.922, sig =
0.000, η2 = 0.199) and the fewest social interactions (mSI = 7.33, F =
5.323, sig. = 0.001, η2 = 0.065) in comparison with employed depressed
persons or not-depressed ones. The employed people (with/without
depression) perform better at UPSA (mD + =81.81, mD- = 81.05). Being
employed without depression symptoms is associated with better
cognitive abilities (mGDS = 0.32), better functioning (mADL = 2.19),
less cognitive complaints (mPAOFI = 0.64) and more social interactions (mSI = 16.48). Being unemployed without depression is associated with a mild cognitive deficit (mGDS = 0.50).
Conclusion
Being employed supports HIV infected people to unravel at practical
activities, have less cognitive complaints, be more functional in
everyday tasks, less depressed, with more social contacts and a better cognitive functioning. Having a job increases person’s functioning
by putting cognitive abilities in action.
BMC Infectious Diseases 2016, Volume 16 Suppl 3
Acknowledgement
NIH-funded grant R01MH094159-01 “Long term effects of chronic HIV
infection on the developing brain”.
O26
Predictors of survival in parenterally-infected HIV positive children
and youth diagnosed with progressive multifocal
leukoencephalopathy
Cosmina Gingăraş1, Ștefan Adrian Anton1, Roxana Rădoi1, Simona
Tetradov1, Grațiela Țârdei2, Maria Nica3, Razvan Alexandru Capşa4,5,
Cristian L. Achim6, Cristiana Oprea1,7, Luminița Ene1
1 th
5 Clinical Department of Infectious Diseases (HIV Department),
“Dr. Victor Babeș” Hospital for Infectious and Tropical Diseases, Bucharest,
Romania; 2Virology, Immunology, Molecular Biology Department,
“Dr. Victor Babeș” Hospital for Infectious and Tropical Diseases, Bucharest,
Romania; 3Microbiology Department, “Dr. Victor Babeș” Hospital for
Infectious and Tropical Diseases, Bucharest, Romania; 4“Dr. Victor Babeș”
Medical Center for Diagnosis and Treatment, Bucharest, Romania;
5
Department of Radiology, Fundeni Institute, Bucharest, Romania; 6UC San
Diego, Departments of Psychiatry and Pathology, La Jolla, CA, USA; 7Carol
Davila University of Medicine and Pharmacy, Bucharest, Romania
Correspondence: Cosmina Gingăraş (cosminagingaras@gmail.com) –
5th Clinical Department of Infectious Diseases (HIV Department), “Dr. Victor
Babeș” Hospital for Infectious and Tropical Diseases, Bucharest, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O26
Background
Progressive multifocal leukoencephalopathy (PML) is a severe opportunistic infection of the central nervous system (CNS), with high mortality and rare spontaneous remissions, even in the setting of highly
active antiretroviral therapy (HAART). We aimed to investigate the
prevalence, outcomes and factors associated with survival in patients
with PML who belong to the cohort of children parenterally-infected
with HIV at the end of the 1980’s in Romania.
Methods
Retrospective chart review of all HIV positive patients parenterallyinfected and diagnosed with PML between 1990-2016 in a tertiary care
center. PML diagnosis was established based on clinical symptoms,
neuroimaging, cerebrospinal fluid (CSF) findings and neurohistological
examination. We performed summary statistics of demographic, clinical
and laboratory collected data. Logistic regression was used to determine predictors of survival at several time points. Data were analyzed
using STATA 11 (College Station, TX, USA).
Results
A total of 46 patients were diagnosed with PML, 45 % before 2006.
Half of the patients were male and the average age at diagnosis
(baseline) was 17.8 years (range: 8.2-27.7) with a bimodal distribution,
with peaks at 11 and 22 years. The median baseline CD4 count was
32.5 cells/uL (IQR: 10-90 cells/uL); median HIV viral load (VL): 5.44 log
copies/mL (IQR: 4.3-5.8); median HIV VL in CSF: 3.5 log copies/mL
(IQR: 2.6-4.2). Twenty-six (58 %) cases were confirmed by JCV PCR.
MRI lesions were supratentorial in 34.9 % of patients, subtentorial in
25.6 %, and mixed in 39.5 %. Seventeen patients (37 %) were alive at
the end of the study. Median survival time was 16 months (range:
one month-15.8 years). Survivors were older at diagnosis and had
better baseline clinical, immunological and virological parameters.
Those who died had a median survival of 2.8 months (IQR: 1.5-13.6)
after PML diagnosis and a preponderance of subtentorial or mixed
lesions on MRI. The strongest predictors of survival at the moment of
diagnosis were baseline CD4 count and VL. Univariate logistic regression analysis identified age at PML diagnosis, baseline viral load and
use of cART before diagnosis as strong predictors of survival beyond
one year from diagnosis, and a marginal significance for use of cART
with greater CNS penetrability scores, but none of these factors
maintained significance in multivariate models.
Conclusions
In our study period, PML was almost as prevalent after the introduction of HAART as it was before. However, being exposed to cART and
Page 12 of 29
having a lower baseline viral load and higher CD4 count were associated with long-term survival.
O27
Neurocognitive and brain functioning in HIV-infected young MSM
treated with cART
Bogna Szymańska1, Natalia Gawron2, Agnieszka Pluta3, Emilia Łojek2,
Ewa Firląg – Burkacka1, Andrzej Horban4, Robert Bornstein5,
et HARMONIA3 Study Group
1
Outpatients Clinic, Hospital for Infectious Diseases in Warsaw, Poland;
2
The Faculty of Psychology, University of Warsaw, Warsaw, Poland;
3
World Hearing Center, Institute of Physiology and Pathology of Hearing,
Nadarzyn, Poland; 4Medical University of Warsaw, Warsaw, Poland;
5
Department of Psychiatry and Behavioral Health, Ohio State University,
Columbus, OH, USA
Correspondence: Bogna Szymańska (bogna.szymanska@gmail.com) –
Outpatients Clinic, Hospital for Infectious Diseases in Warsaw, Poland
BMC Infectious Diseases 2016, 16(Suppl 3):O27
Background
There is growing evidence that despite successful antiretroviral treatment, neurocognitive and brain dysfunctions can be still observable
in HIV-infected individuals. The aim of this study was to investigate
neurocognitive and brain functioning in young HIV(+) MSM, treated
with cART, with undetectable HIV1-RNA in serum.
Methods
Fifty HIV(+) individuals and 42 HIV(-) controls aged 20-40, compared
on socio-demographic variables were analyzed in this study. The
characteristics of HIV(+) group were as follows: duration of HIV infection M = 3.7 years, SD = 3.2; CD4 + nadir M = 311 cells/μL, SD = 125;
CD4+ current M = 599 cells/μL, SD = 193; duration of cART M =
2.9 years, SD = 2.9; 54 % were diagnosed with STD (syphilis) in the
past. They were treated with ARV for a minimum 10 months. We analyzed 3 types of cART regimens: 2NRTI + PI/r, 2NRTI + NNRTI and
other regimens. Out of both groups, 30 HIV(+) and 27 HIV(-) individuals were examined on the n-back task in 3-Tesla MRI Scanner. The
participants were performed a battery of neuropsychological tests
and psychological questionnaires.
Results
Despite preserved abilities on general mental status, intelligence, reasoning, language, psychomotor skills and mood, HIV(+) individuals
showed significant impairment comparing with the controls in the
domains of working memory, psychomotor speed, attention and executive function: VMS Forward (p < 0.05) and Backward (p < 0.002),
WAIS Digit Span (p < 0.002), RFFT (p < 0.002), WCST (p < 0.05). We
have not observed differences between cART regiments. In the psychological questionnaires HIV(+)MSM exposed better coping strategy
(KPD) (p < 0.05), greater social activity (SAQ) (p < 0.004), social support (SSQ) (p < 0.05) and stronger masculine features than controls
(PAQ) (p < 0.001).
Although similarities of the results in the n-back task, the patterns
of brain activation during that task in fMRI were different in both
groups. Bilateral activation was observed in the middle frontal
gyrus, insula, putamen, thalamus and the parietal lobule in both
groups. Whereas the controls showed increased activation in superior parietal lobule in right hemisphere in comparison with HIV(+)
individuals.
Conclusion
Young HIV(+) MSM presented selected deficits in working memory,
psychomotor abilities, attention and executive domains although
good psychological factors. They also showed slight changes in brain
activity during the fMRI task. Thus despite effective cART HIV(+) MSM
manifested changes in the neurocognitive, psychological and brain
functioning comparing with the controls.
Acknowledgement
1. Hospital for Infectious Diseases in Warsaw, Poland.
2. The Faculty of Psychology, University of Warsaw, Poland.
BMC Infectious Diseases 2016, Volume 16 Suppl 3
O28
Clinical value of RT-PCR detection of Toxoplasma gondii DNA in
cerebrospinal fluid
Olivia Burcoș1, Simona Manuela Erscoiu2, Filofteia Bănicioiu Cojanu1,
Andreea Toderan1, Maria Nica2, Ionuț Cristian Popa1, Emanoil Ceaușu2,
Petre Iacob Calistru2
1
Clinical Hospital for Infectious and Tropical Diseases “Dr. Victor Babeș”,
Bucharest, Romania; 2Carol Davila University of Medicine and Pharmacy,
Bucharest, Romania
Correspondence: Olivia Burcoș (olivia_burcos@yahoo.com) – Clinical
Hospital for Infectious and Tropical Diseases “Dr. Victor Babeș”,
Bucharest, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O28
Background
Toxoplasma gondii encephalitis (TE) in HIV infected patients is a severe and frequent opportunistic infection, even in highly active antiretroviral era. Magnetic resonance imaging (MRI) is often suggestive,
but sometimes the differential diagnosis of cerebral mass can be very
difficult. Sensitivity of the PCR in CSF in the literature ranges between
33-100 % and specificity between 94-100 %. We calculated these
constants in our clinic.
Method
Probable toxoplasmosis was defined as neurological symptoms appeared in HIV patients, with typical MRI and favorable outcome
under etiologic therapy. Data were collected retrospectively from
January 2012 to January 2016. A control group consisted of HIV patients with no personal history of TE, confirmed with other central
nervous system conditions (HIV encephalopathy, progressive multifocal leukoencephalopathy, cryptococcal or tuberculous meningitis,
cerebral lymphoma-confirmed by RT-PCR of JC virus, Mycobacterium
or Cryptococcus cultures, pathologic examination), and no additional
lesions suggestive for TE coinfection. Lumbar puncture was performed in the first day after the diagnosis (media 0.47 days). For RTPCR technique was used nucleic acid extraction kit straight from CSF,
Master Pure Complete DNA&RNA Purification Kit (Illumina), commercial primer Primerdesign genesig Kit for Toxoplasma gondii genomes
and Light Scanner 32 Instrument (Idaho Technologies, USA). Chemiluminescense method was used for serologic tests.
For RT-PCR technique was used nucleic acid extraction kit straight
from EDTA blood, Master Pure Complete DNA&RNA Purification Kit/
Epicentre Biotechnologies, commercial primer Primer Design UK and
Light Scanner 32/Idaho Technologies.
Results
RT-PCR for Toxoplasma was performed in the CSF of 23 patients (out
33 suspected cases of TE). Only in 3 cases the RT-PCR was negative
(one of them had a positive RT-PCR in the brain biopsy). 7 patients
with compatible symptoms and characteristic MRI, with positive RTPCR for Toxoplasma in CSF, died of severe disease and were excluded
from the study. Serologic tests for Toxoplasma (IgG) in the plasma
were positive (18 of 23 tested) and all serologic tests in CSF were
negative (10 out of 23 tested). 17 patients with other neurologic conditions were selected for the control group. All had negative RT-PCR
in the CSF. The calculated sensitivity of the RT-PCR for Toxoplasma
gondii in CSF was 84.2 %, 100 % specificity, positive predictive value
100 % and negative predictive value 85 %.
Conclusion
RT-PCR for Toxoplasma gondii in CSF is a good diagnostic method
compared to CSF serologic tests, and relatively non invasive compared to brain biopsy.
O29
Characteristics of sleep disorders in Romanian adults infected with
human immunodeficiency virus
Manuela Arbune1, Mirela Alexandrache2, Anca-Adriana Arbune3,
Doina-Carina Voinescu1
1
Clinical Department, “Dunărea de Jos” University Galați, Galați, Romania;
2
Infectious Diseases Clinical Hospital Iași, Iași, Romania; 3Clinical
Department 6, Carol Davila University of Medicine and Pharmacy,
Bucharest, Romania
Page 13 of 29
Correspondence: Manuela Arbune (manuela.arbune@ugal.ro) – Clinical
Department, “Dunărea de Jos” University Galați, Galați, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O29
Background
Sleep disorders are common symptoms in chronic diseases and contribute to decreased quality of life. Increased frequency of sleep disorders in patients with HIV infection was associated with reduced
slow-wave sleep, but the influence of immunosuppression, opportunistic diseases or antiretroviral drugs (Efavirenz) is controversial. The
aim of the study is to characterize the sleep problems in a group of
Romanian HIV seropositive patients.
Methods
A cross sectional study assessed the sleep disorders by self-report of
Epworth sleep questionnaire and Pittsburgh Sleep Quality Index with
seven domains: subjective sleep quality, sleep latency, sleep duration,
habitual sleep efficiency, sleep disturbances, use of sleeping medication and daytime dysfunction. Patients with PSQI ≥5 were diagnosed
with poor sleep quality. Demographic data, antiretroviral therapy,
Beck-II depression score, CD4 cell count were collected from medical
records. Exclusion criteria were illiteracy and severe or moderate depression (Beck-II score >18). Categorical variables as gender, marital
status category, medication group category, CD4 cell count category
below or above 200 cells/cmm, Beck score bellow or above 13, are
presented as frequencies (%) and group differences compared using
Chi2 test, with the significance level <0.05.
Results
The characteristics of patients were age 30.66 ± 6.86, 50.6 % males,
56.6 % urban living area, 49.3 % married/stable relationship, 16.8 %
employed. Most patients had immunity LCD4 > 500 cells/cmm (56.2 %).
Risk factors of sleep disorder were: smoking (46.9 %), hypertension
(21.69 %), obesity (12.05 %), depression (33.73 % scoring Beck-II between 13 and 18), snoring (36.14 %). Epworth score was 5.20 ± 4.34
while 26.25 % patients with values >7 have the risk to fall asleep during
the daytime. The mean PSQI value was 4.89 ± 2.89 and 49.4 % patients
associate sleep dysfunctions. Sleep disturbance and daytime dysfunctions were the main disorders. The PSQI global score was correlated
with age and level of immunity. Snoring was correlated with age,
hypertension and obesity. Patients with Efavirenz treatment have reported frequently daytime dysfunction and sleeping pills use.
Conclusions
Practically half of adult patients with HIV infection under age 50 have
sleep problems and negative impact on daily functioning. The strategy to prevent and control those disorders in the coming years
should consider the effective and less neurotoxicity antiretroviral
therapy, the psychological support, hypertension and obesity care.
O30
Diagnosing neuroHIV: the rift between clinicians and pathologists
Ioan-Alexandru Diaconu1†, Laurențiu Stratan1†, Victoria Aramă1,2,
Luciana Nichita3, Alexandra Diaconu4, Anca Negru1,2, Alina Orfanu1,2,
Anca Leuștean1, Daniela Adriana Ion1,2
1
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest,
Romania; 2Carol Davila University of Medicine and Pharmacy, Bucharest,
Romania; 3Colentina Clinical Hospital, Bucharest, Romania; 4“Marius
Nasta” Pneumophtisiology Institute, Bucharest, Romania
Correspondence: Ioan-Alexandru Diaconu (diaconuia@yahoo.com) –
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest,
Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O30
†
The authors had equal participation.
Background
There has been little research conducted in Romania regarding the
neurological complications that arise from infection with the human
immunodeficiency virus 1 (HIV-1), from a histopathologist’s point of
view. Our study aims to create an extensive record of HIV-induced central nervous system involvement through post-mortem histopathological examination, immunohistochemistry and immunofluorescence
in correlation with clinical diagnoses issued ante mortem.
BMC Infectious Diseases 2016, Volume 16 Suppl 3
Methods
The investigated material consisted entirely of human brain tissue
samples collected during some of the autopsies conducted in the
Pathology Department of Colentina Clinical Hospital, Bucharest, over
a time span longer than 22 years (1993 - 2015) on 39 HIV+ patients
hospitalized in the National Institute for Infectious Diseases “Prof. Dr.
Matei Balș”. All cases were examined concurrently by two pathologists and quantified by common criteria in order to ensure a uniform
assessment of the studied material.
Results
The group, composed of 39 HIV-positive patients, was created during
a period of over 22 years and show marked heterogeneity, both in
age, variety of diagnoses, treatment, as well as immunological status.
From the group of 39 HIV-infected patients whose brain tissue was
examined post-mortem, a third received antiretroviral therapy, 10 %
of them for less than 5 months. The most common clinical diagnoses
were bronchial pneumonia, oropharyngeal candidiasis, meningoencephalitis, pulmonary tuberculosis and HIV encephalopathy. The
most common neurological histopathological diagnoses were
hyperemia with edema, cryptococcal meningoencephalitis and HIV
encephalopathy. In the non-cART branch, the top neurological histopathology diagnoses were hyperemia with edema, non-specific meningoencephalitis and cryptococcal meningoencephalitis. Hyperemia
and edema was discovered in 20 % of the patients, with only a few
being treated with antiretroviral therapy.
Conclusions
The results revealed that some of the clinical diagnoses, despite the
use of modern methods of imaging and serological investigation, are
inconsistent with the neurohistopathological findings, due to the
heightened difficulty of the differential diagnosis. This situation is
caused by the myriad of effects brought about by the HIV infection,
illustrating the origin of a 60 % accuracy of diagnosis.
O31
A challenging neurological complication in a HIV-infected young
woman with multiple opportunistic infections
Irina Ianache1, Cristiana Oprea1,2
1 th
5 Clinical Department for Infectious Diseases (HIV Department), “Dr. Victor
Babeș” Hospital for Infectious and Tropical Diseases, Bucharest, Romania;
2
Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
Correspondence: Irina Ianache (ianacheirina@gmail.com) – 5th Clinical
Department for Infectious Diseases (HIV Department), “Dr. Victor Babeș”
Hospital for Infectious and Tropical Diseases, Bucharest, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O31
Background
Diagnosis of CNS immune reconstitution inflammatory syndrome
(IRIS) is still an important challenge for the management of HIVinfected patients.
Case description
We present the case of a 25 year-old woman, who acquired HIV infection by parenteral mode (in the first years of life) and had a history of poor adherence to cART.
She was diagnosed with pulmonary tuberculosis (TB) with positive
cultures in July 2013, but abandoned anti TB treatment shortly (after
one month).
She was admitted in our department in January 2014, with fever, severe respiratory failure and left hemiparesis. The lab screen showed
severe anemia, hypoxemia, increased LDH levels, severe immunosuppression (CD4 cell count - 9 /cmm) and high plasma viral load (VL)
(5.92 log10 copies/mL). Pneumocystis jirovecii pneumonia (PCP) and
pulmonary TB were diagnosed (chest X-rays and bacteriological
exams). TB treatment and cotrimoxazole were initiated, with improvement of the respiratory symptoms but persistence of the
neurological deficits. Brain MRI showed a hypo-intense round lesion
on T1-sequence in the right parietal region, hyper-intense on T2, with
ring enhancement and important edema, suggestive for cerebral
toxoplasmosis. Cerebrospinal fluid (CSF) exam was unremarkable,
with negative MTB cultures and negative PCR-DNA tests for both TB
and toxoplasmosis. Serology for Toxoplasma gondii (IgG) was positive
Page 14 of 29
in plasma and CSF. After 6 weeks of cotrimoxazole and anti TB treatment and 3 weeks of cART (with integrase inhibitors) she was discharged with favorable clinical evolution and improved brain
neuroimaging. Two months later, she was readmitted in our department with headache, generalized seizures, left hemiplegia and left facial palsy. We noticed an important increase in CD4 cell count (111/
cmm) and a significant decrease in HIV-VL (2.5 log10 copies/mL).
Brain MRI showed an increase in size and number of the cerebral
lesions (parietal and frontal areas), with important edema, greater
contrast enhancement in T1 and mass effect on the right lateral ventricle. Non-adherence to anti-toxoplasma treatment and resistance to
cotrimoxazole were excluded. Paradoxical Toxoplasma IRIS was the
most probable diagnosis in a patient with important immunological
recovery, significant VL decrease after two months of cART, suggestive MRI imaging and increased inflammatory markers in plasma.
Clinical evolution was favorable after continuing anti-toxoplasma
treatment with pyrimethamine, sulphadiazine combined with corticotherapy with regression in size and number of the cerebral lesions.
Conclusion
We describe a particular case of paradoxical toxoplasma IRIS in a
woman with multiple concomitant opportunistic infections.
Consent
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of
the written consent is available for review by the Editor of this
journal.
O32
Brain abscess with uncertain etiology in a late-presenter HIV
infected patient
Anca Leuștean1, Cristina Popescu1,2, Alina Orfanu1,2, Anca Negru1,2,
Remulus Catana1,2, Cristina Murariu1, Ioan-Alexandru Diaconu1,2,
Mihaela Rădulescu1,2, Cătălin Tilișcan1,2, Victoria Aramă1,2
1
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”,
Bucharest, Romania; 2Carol Davila University of Medicine and Pharmacy,
Bucharest, Romania
Correspondence: Anca Leuștean (anca_leustean@yahoo.com) –
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest,
Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O32
Background
CNS infection in HIV patients may occur during any stage but most
frequent if CD4 count is below 200 cells/cmm. The onset of this infection can be acute, subacute or chronic and the most common etiology could be: toxoplasmosis (T), cryptococcal infection, primary
CNS lymphoma (PL), progressive multifocal leukoencephalopathy
(PML), AIDS dementia complex or CMV infection.
Case presentation
A 19-year old female was admitted in our clinic to investigate and
stage a recently discovered HIV infection. She first presented to another hospital for fever, fainting, headache, paraesthesia in her lower
limbs and fatigue. The laboratory results showed pancytopenia and a
positive test for HIV. On admission in our clinic, the patient was
afebrile, without neck stiffness but with positive Kernig sign and a
slight facial asymmetry. The laboratory results confirmed an HIV infection with a CD4 count of 42 cells/cmm, an HIV viral load of
295807 copies/ml, positive IgG and negative IgM for Toxoplasma
gondii and Cytomegalovirus, negative Quantiferon-TB, VDRL, IgM for
Herpes Simplex and hepatitis viruses. We performed a lumbar puncture which showed clear, hypertensive cerebrospinal fluid (CSF) with
15 cells/cmm, positive Pandy reaction, elevated protein level
(129 mg %), glucose level 26 mg % (serum glucose level 68 mg %),
normal lactic acid, negative Cryptoccocus, negative PCR for Mycobacterium and an HIV viral load in CSF of 347752 copies/ml. The CT scan
showed a low-density area of 2.8/2.1 cm, with peripheral contrast
and important surrounding edema, localized in the capsule-lenticular
and left parietal structures, with a mass effect and deviation of the
median line structures to the right by 6 mm, interpreted as a cerebral
abscess. The CT scan was repeated with cerebral perfusion to rule
BMC Infectious Diseases 2016, Volume 16 Suppl 3
out a cerebral lymphoma. The possible etiologies taken into consideration were: pyogenic brain abscess, cerebral toxoplasmosis, cerebral tuberculosis, Herpes Simplex Virus infection and cerebral
lymphoma. The antimicrobial treatment consisted in ceftriaxone
(2gx2/day), vancomycin (1gx2/day) for 14 days, cotrimoxazole 12 tablets/day, intravenous acyclovir 500mgx2/day and also MAC prophylaxis with clarithromycin. After 7 days of treatment, the CT scan
showed an improvement of the cerebral lesions. The treatment with
cotrimoxazole 12 tablets/day was stopped after 3 weeks because of
the aggravation of her pancytopenia. Given the high HIV viral load in
the CSF and the low CD4 count, with a negative HLA-B5701, the antiretroviral therapy (ART) was initiated with Efavirenz and Abacavir/
3TC, without any signs of Immune Reconstruction Inflammatory Syndrome (IRIS). The third CT scan (2 months later) showed a 6 mm lowdensity sechelar lesion lateral of the caudate nucleus, without any
mass effect. After another two months, the CT scan showed the same
sechelar lesion. Also, the hemogram was normal and the CD4 count
was of 426 cells/cmm. The lumbar puncture was repeated, with a
slightly hypertensive CSF, slightly elevated protein level and normal
glucose and lactic acid levels and an HIV viral load in the CSF of 88
copies/mL.
Conclusion
Although in HIV infected patients with cerebral abscess toxoplasmosis is the most frequent etiology, pyogenic abscess must be taken
into account. A less aggressive ART as a first regimen can sometimes
avoid IRIS in a patient with very low CD4 count.
Consent
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of
the written consent is available for review by the Editor of this
journal.
Page 15 of 29
the lingual swabs showed Candida albicans >10 CFU. Serum electrolytes, liver and kidney function tests were normal. CT scan of the
brain showed: hypodense areas, a fluid density image with a diameter of 2.2/1 cm in core lentiform left nuclei, a 1.5/2.2 cm image in
the right lentiform nuclei in the right saphenous capsule (1/0.5 cm).
Neurological exam revealed: conscious patient, cooperant, without
neck stiffness, walking is possible with support, crural monoparesis,
left Babinski reflex-plantar cutaneous left without objectives sensitivity disorders, upper limb myoclonus as predominantly left postural
action, anisocoric mild cranial nerves (right > left). Diagnosis: crural
monoparesis left upper limb myoclonus, right cerebral toxoplasmosis.
Despite the complex therapy instituted (clindamycin, pyrimethamine,
mannitol, glucose 10 %, NaCl 0.9 %, fluconazole, levetiracetam, dexamethasone, ARV, etc.), overall condition was aggravated, the patient
becomes uncooperative, with progressive dysphagia for solids and
liquids, with periods of unconsciousness and finally with unfavorable
evolution.
Conclusion
Late diagnosis of opportunistic brain infections in HIV-infected and
nonadherent patients, despite a complex rescue therapy may be associated frequently with unfavorable evolution of these patients. It is
required a rigorous therapeutic clinical monitoring, along with a repeated psychological counseling of patients with ARV treatment.
Consent
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of
the written consent is available for review by the Editor of this
journal.
O33
Cerebral toxoplasmosis and left crural monoparesis with fatal
evolution in a noncompliant patient with AIDS C3
Iosif Marincu1, Patricia Poptelecan1, Valeria Bică1, Florin Lazăr2,
Livius Tirnea1
1
Department of Infectious Diseases, Pneumology, Epidemiology and
Parasitology, “Victor Babeș” University of Medicine and Pharmacy,
Timișoara, Romania; 2Faculty of Sociology and Social Work, University of
Bucharest, Bucharest, Romania
Correspondence: Iosif Marincu (imarincu@umft.ro) – Department of
Infectious Diseases, Pneumology, Epidemiology and Parasitology, “Victor
Babeș” University of Medicine and Pharmacy, Timișoara, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O33
O34
Opportunistic infections still a problem in HIV-infected patients in
cART era: a Romanian single center experience
Irina Ianache1, Roxana Rădoi1, Manuela Nica2,4, Grațiela Țârdei3, Luminița
Ene1, Emanoil Ceaușu1,4, Petre Calistru1,4, Cristiana Oprea1,4
1
5th Clinical Department for Infectious Diseases (HIV Department), “Dr
Victor Babeș” Hospital for Infectious and Tropical Diseases, Bucharest,
Romania; 2Laboratory of Microbiology, “Dr Victor Babeș” Hospital for
Infectious and Tropical Diseases, Bucharest, Romania; 3Laboratory of
Virology, Immunology, Molecular Biology, “Dr Victor Babeș” Hospital for
Infectious and Tropical Diseases, Bucharest, Romania; 4Carol Davila
University of Medicine and Pharmacy, Bucharest, Romania
Correspondence: Irina Ianache (ianacheirina@yahoo.ca) – 5th Clinical
Department for Infectious Diseases (HIV Department), “Dr Victor Babeș”
Hospital for Infectious and Tropical Diseases, Bucharest, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):O34
Background
Cerebral toxoplasmosis remains the most frequent neurological opportunistic infection in patients with HIV/AIDS. We present a clinical
case of cerebral toxoplasmosis with fatal evolution in an unadherent
patient with C3 stage AIDS.
Case report
A 31 years old female patient coming from a rural area, diagnosed
with HIV Infection 2 years before, was hospitalized in the Clinic of Infectious Diseases Timișoara, accusing: dysphagia for solids and liquids, poor motor function, left hemiparesis and left facial paralysis,
paleness of skin, fatigue, loss of appetite. The patient is noncompliant at the antiretroviral (ARV) therapy and has a reduced level of
medical education. The positive diagnosis was based on clinical elements (the altered general condition, conscious, with left facial paralysis, pallor, lingual candidiasis, etc.), the biological samples (blood
cell identification, erythrocyte sedimentation rate (ESR), glucose, Creactive protein (CRP), blood cultures, CD4 count, viral load (VL),
Toxoplasma IgG and IgM antibodies, etc.) and paraclinical investigations (chest radiography, brain computed tomography (CT) scan,
abdominal ultrasound). Biological samples were analyzed in the hospital laboratory.
From the blood tests we highlight: total white blood cell 2930/μL, Hb
10.5 g/dl, CRP 95.69 mg/L, ESR 85 mm/1st hour, Toxoplasma IgG Ab
282 U/mL, CD4 count 31 cells/μL, VL 590381 copies/mL, cultures from
Background
Despite significant improvement of AIDS-related morbidity and mortality in the cART era, the incidence of opportunistic infections (OIs)
in HIV-infected patients in some middle income countries is still high.
The aim of our study was to evaluate the incidence, demographics
and outcome in patients diagnosed with OIs in a tertiary HIV care
center.
Methods
Prospective study on HIV-infected patients diagnosed with OIs at
“Victor Babeș” Hospital between January 2011 and December 2015.
Diagnosis of OIs was definitive in cases with positive microbiological
exams or presumptive (typical clinical, epidemiological, imaging techniques). Statistical comparison between OIs groups was performed
using SPSS v 19.0, survival being compared using Kaplan Meier
methods.
Results
Out of 5,728 person-years (PY), 250 HIV-infected patients were diagnosed with 314 OIs (incidence 54.8/1000 PY). The majority 169
(67.6 %) were males, with a median age at OIs diagnosis of 28 years
(IQR: 25-37). The route of HIV transmission was: heterosexual 35.6 %
(HSX), due to injecting drug use 32.0 % (IDUs), by parenteral mode
during childhood 28.8 % (PI), MSM 2.0 % and from mother-to-child
1.6 %. The incidence of OIs increased from 3.5 % in 2011 to 7.0 % in
2015 (p = 0.0005).
BMC Infectious Diseases 2016, Volume 16 Suppl 3
The median CD4 cell count/cmm and HIV viral load (copies/mL) at OIs
diagnosis was 41 (IQR: 16-136) and 5.19 log10 (IQR 3.91-5.67) respectively. In 111 cases (35.3 %) HIV and OI were diagnosed simultaneously
and among 143 patients who developed OIs on cART, 84.6 % were
non-adherent. The most common OIs were: tuberculosis (TB) 187
(59.5 %), progressive multifocal leukoencephalopathy (PML) 39
(12.4 %), Pneumocystis jirovecii pneumonia 23 (7.3 %), cerebral toxoplasmosis 22 (7.0 %), esophageal candidiasis 19 (6.0 %), cryptococcal meningitis (CM) 12 (3.8 %) and other 12 (3.8 %). TB was more frequent in
IDUs compared to HSX and PI (43.3 % vs 31.0 % vs 22.9 % p < 0.0001),
the latest developing more often cerebral toxoplasmosis (p = 0.0008)
and PML (p < 0.0001). Patients diagnosed with CM had the lowest CD4
cell count/cmm at diagnosis (12, p = 0.005). PI patients were younger
(median years) at OIs and HIV diagnosis compared to HSX and IDUs
(25, 9 vs 38, 33 vs 30, 29 respectively, p < 0.0001). The overall mortality
rate was high (27.0 %). IDUs had lower median survival time (months)
compared to HSX and PI (10.5 vs 16.7 vs 17.8 respectively, p = 0.002).
Conclusions
The incidence of OIs during the study period was high, TB being predominant. OIs are still contributing to the increased HIV-related morbidity and mortality, due to late presentations and/or non-adherence
to cART.
POSTER PRESENTATIONS
P1
Epidemiological aspects of co-infection of HIV/TB in Moldova
Iurie Osoianu, Ala Halacu
National Center of Public Health, Chișinău, Republic of Moldova
Correspondence: Iurie Osoianu (iurieosoianu@gmail.com) – National
Center of Public Health, Chișinău, Republic of Moldova
BMC Infectious Diseases 2016, 16(Suppl 3):P1
Purpose
To assess and study epidemiological particularities of co-infection of
HIV/TB and associated risk factors to provide appropriate recommendations directed to optimize the existing system of epidemiological
surveillance and control of these infections.
Objectives
- To study epidemiological particularities of co-infection of HIV/TB in
the Republic of Moldova associated with occupation, geographic
area, sex, age, social and behavioral factors, and identify the prevalent factors;
- Identify risk factors associated with TB/HIV cases;
- Provide recommendations directed to improve surveillance systems
of these infections.
Materials and methods
Cross-sectional study, conducted by interviewing 321 persons with
coinfection of HIV/TB during 2013-2014.
Results
71.2 percent are men, mean age 37 years; 72 percent live in urban
areas and 4.7 percent - do not have stable place of life; 85 percent
do not work. 84.4 percent (±3.82) have a history or are present intravenous drug users. Only 2.6 percent (±4.98) are on opioid substituent
treatment during TB treatment. 37 percent (±4.47) had experienced
or are heavy drinkers (53 percent are undocumented on alcohol use).
34 percent (±5.38) experienced or are in current detention. 28.9 percent (±4.78) were out of the country before TB case notification. 56
percent (±5.31) have at least one co-morbidity; 33 percent of them
have hepatitis C and 14 percent hepatitis B. No one received preventive treatment with isoniazid. There is a growing share of new
registered HIV/TB cases in the Republic of Moldova in recent years.
Conclusions
Patients with TB/HIV are the most vulnerable to the higher proportion of people living with HIV and affected by social vulnerabilities
Page 16 of 29
and risk factors and require careful management of the case. Most of
the cases were associated with drug use, few were opioid substituent
treatment during TB and HIV treatment, which could increase adherence to TB treatment and ARVs. A significant proportion of patients
are outside the viewfinder profile institution or occur in late stages of
HIV disease. A significant proportion of patients have history of alcohol consumption and detention.
P2
Perinatal exposure at HIV infection in Oltenia region
Andreea Cristina Stoian1, Florentina Dumitrescu1, Iulian Diaconescu1,
Augustin Cupșa1, Lucian Giubelan1, Loredana Ionescu2, Irina Niculescu1
1
Department of Infectious Diseases, University of Medicine and
Pharmacy from Craiova, Craiova, Romania; 2Clinical Hospital of Infectious
Diseases from Craiova, Craiova, Romania
Correspondence: Andreea Cristina Stoian (andreea_plr@yahoo.com) –
Department of Infectious Diseases, University of Medicine and Pharmacy
from Craiova, Craiova, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P2
Background
Through the correct implementation of the preventive measures, the
maternal transmission of HIV infection can be reduced to <2 %. The
aim of the study is the epidemiological analysis of mother-to-child
transmission of HIV in Oltenia region (Dolj, Olt, Mehedinți and Gorj
counties).
Methods
Retrospective study in the Regional Centre for Monitoring and Evaluation of HIV/AIDS in Craiova, between 01/01/2004-31/12/2015 on a
group of 131 children born of mothers HIV infected. There were analyzed: the moment of the mother’s HIV diagnosis, the mother’s
immuno-virological status, birth method, antiretroviral (ARV) treatment and the modality of the child’s alimentation. The statistical analysis used Epi Info programme, the p value being statistically
significant at <0.05.
Results
Demographics: the group of 131 children, F/M = 63 (48.09 %)/68
(51.91 %); U/R = 46 (35.12 %) /91 (64.88 %). Chronological distribution of the births showed a top of incidence in 2009 (19 births14.51 %) and in 2007 (17 births-12.98 %), with an upward linear
trend. The mother who was infected with HIV from the parenteral
group in 1987-1990 period, was 105 (80.16 %), 24 mothers
(18.33 %) were infected with HIV sexually, 1 (0.77 %) drugs consuming pregnant woman and 1 (0.77 %) pregnant woman, with unknown HIV transmission. Viral-immune evaluation of pregnant
women (with 1-3 months before birth) showed average of lymphocytes CD4 = 443.147 ± 32.52 cells/cmm and an average of viremia
HIV = 35051 copies/mL (4.54 log copies/mL). The method of birth
was: natural birth in 26 cases (19.85 %) and 105 (80.16 %) mother
through a cesarean. Antiretroviral treatment was gotten by 105
pregnant women (80.16 %), the most used schedule being: CBV +
LPV/r = 84 (80 %). Artificial alimentation was administered to 117
children (89.32 %), the postpartum ARV prophylaxis was administrated to 120 children (91.61 %). During the survey period, 11 children (8.39 %) were diagnosed with HIV; 2 children (1.52 %) are still
being evaluated. The characteristics of children HIV infected were: 5
children naturally born (p = 0.04), 3 children without ARV postpartum (p = 0.02), 6 children with artificial alimentation (p = 0.0010)
and 7 mothers without ARV treatment (p = 0.002)
Conclusions
In Oltenia region there was registered a progressive trend, upwards
for children born of HIV infected mothers, most of them coming from
the parenteral infected cohort, with a high transmission rate, according to the lack of complete preventing measures of materno-fetal
transmission.
BMC Infectious Diseases 2016, Volume 16 Suppl 3
P3
Women living with HIV in Mureș county
Carmen Chiriac1, Nina Șincu1, Iringo Zaharia Kezdi1, Anca Georgescu1,
Brândușa Țilea1, Cristina Girbovan1, Andrea Incze1, Andrea Fodor2
1
Department of Infectious Diseases, University of Medicine and
Pharmacy Tîrgu-Mureș, Tîrgu-Mureș, Romania; 2Department of
Laboratory Medicine, University of Medicine and Pharmacy Tîrgu-Mureș,
Tîrgu-Mureș, Romania
Correspondence: Carmen Chiriac (carmen.l.chiriac@gmail.com) –
Department of Infectious Diseases, University of Medicine and Pharmacy
Tîrgu-Mureș, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P3
Background
Women infected with human immunodeficiency virus (HIV) represent
one of the important phenomena in the present HIV pandemics. The
natural hormonal, emotional and social changes represent a supplementary burden in HIV-infected women compared to men.
Methods
We performed a cross-sectional observational study regarding the
women infected with HIV currently monitored in Mureș Regional
HIV/AIDS Center. We collected data regarding the patients’ sociodemographic features, immunologic and virologic status, the impact
of antiretroviral therapy, correlated with adherence, on the patients’
outcome and the risk of HIV transmission via vertical route.
Results
414 HIV-infected patients are monitored in Mureș Regional HIV/AIDS
Center, 42.27 % of them women, out of which 94.28 % are of fertile
age. As a peculiar feature of this group, 63.42 % of the female patients are long-term survivors, infected with HIV clade F1 during
childhood. 85.14 % of all HIV-infected women and 84.24 % of patients of fertile age receive HAART. In female patients of fertile age,
the median CD4+ T-cells count was 518 cells/μL, compared to a median of CD4+ T-lymphocytes of 519 cells/μL in men (p = 0.6633).
50.96 % HIV-infected female patients and 52.30 % men had undetectable HIV-RNA plasma viral load (p = 0.8378). In December 2015,
78 infants had been born to HIV-infected mothers from Mureș Regional Center during the past 10 years, 62 (87.17 %) of them born to
mothers with long history of HIV infection. Mother-to-infant transmission of HIV infection occurred in 3 cases (3.84 %).
Conclusions
The long-term surviving female patients infected with HIV clade F
have undergone major biological transformations in the natural evolution of women, from childhood to childbirth, due to effective antiretroviral therapy and monitoring. A new generation of HIV-negative
children was born to HIV-infected mothers.
P4
Late diagnosis of HIV infection in children - a challenge for
Romania
Alina Cibea1, Mariana Mărdărescu1, Cristina Petre1, Ruxandra
Drăghicenoiu1, Rodica Ungurianu1, Ana Maria Tudor1,2, Delia Vlad1,
Carina Matei1
1
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest,
Romania; 2Carol Davila University of Medicine and Pharmacy, Bucharest,
Romania
Correspondence: Alina Cibea (a_cibea@yahoo.com) – National Institute
for Infectious Diseases “Prof. Dr. Matei Balș” Bucharest, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P4
Background
In the past few years, the percentage of mother-to-child transmission
of HIV in Romania has remained under 4 %, similar to the percentage
reported for the European Union. This is a proof that the National
Program of Prevention and Control of HIV infection in Romania has
really worked. However, there are still children who are diagnosed
with HIV infection after their first months of life.
Objective
To assess some pediatric cases of late HIV diagnosis (after the neonatal period).
Page 17 of 29
Material and method
Medical records of 13 children, aged 3 months to 9 years, hospitalized in the NIID “Prof. Dr. Matei Balș” in the period Jan 2013 - Oct
2015 have been analyzed. The evaluated parameters: age at diagnosis, HIV status in child’s family, associated HIV diseases, CDC stage of
HIV infection at diagnosis, number of previous confinements, and
evolution of patients with antiretroviral treatment.
Results
10 of the 13 children (77 %) were diagnosed with advanced HIV infection and 5 of these (50 %) were hospitalized for a period longer
than 1 week on over 5 occasions before diagnosis. Among the associated diseases at diagnosis have been mostly opportunistic infections: tuberculosis, fungal infections and pneumocystosis.
Conclusions
Thanks to the prevention program of mother-to-child HIV transmission, Romania has a low percentage of perinatally acquired HIV infection. Nevertheless, children may still be diagnosed late, due to: lack
of compliance with medical care during pregnancy - the pregnant
woman and the new-born are not tested, lack of routine HIV testing for children with multiple confinements for various intercurrent illnesses.
P5
Cirrhosis Assessment in Patients Co-infected HIV-Hepatitis B Virus
Elena Dumea1,2, Lucian Cristian Petcu2, Simona Claudia Cambrea1,2
1
Ovidius University, Constanța, Romania; 2Infectious Diseases Clinical
Hospital, Constanța, Romania
Correspondence: Elena Dumea (elenadumea@yahoo.com) – Ovidius
University, Constanța, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P5
Background and aims
In HIV-infected patients, due to a decrease in AIDS related-deaths,
liver disease is now one of the most common causes of death. It is
necessary to find cheap, accessible tools to assess the amount and
progression of liver fibrosis and the risk for cirrhosis. We chose to use
as non-invasive bio-markers for liver damage APRI and FIB-4 because
these are easily calculated scores from the usual tests of laboratory,
that can be performed periodically and could be a method of assessing longitudinal progression of liver disease in the absence of other
methods invasive or more expensive or which would require special
equipment as transient elastography (FibroScan).
Methods
We evaluated FIB-4 and APRI’s ability to differentiate between cirrhosis (F4 Metavir) and non-cirrhosis (F < 4) taking as a reference value
Fibro-Scan. We used as cut-off Fibro-scan to differentiate cirrhosis
F4 > 12.5kPa. The APRI score is calculated using the patient's aspartate aminotransferase (AST) level and platelet count (PLT), and the
upper limit of normal of AST and FIB-4 results has generated utilizing
age, AST, alanine aminotransferase and PLT. AUROC was used to calculate the optimal value for each score to Identify significant fibrosis.
We studied 71 patients with a documented mean of HIV and hepatitis co-infection duration of 14.2 years, possible infected in early
childhood.
Results
AUROC for APRI to identify cirrhosis was 0.942 95 % CI (0.860, 0.983),
P <0.0001. Cut-off value for APRI in detection of cirrhosis in patients
with HIV + HBV infection with maximum sensitivity and specificity
was established > 1.49 (specificity 96.9 %).
AUROC for FIB-4 for identifying cirrhosis was 0.931 95 % CI (0.845,
0.977), P <0.0001. Cut-off value for detection of cirrhosis for FIB-4 in
HIV + HBV patients with maximum sensitivity and specificity was > 1.3
(96.9 % specificity).
There is a difference between areas of 0.011 with a p 0.792. There is
sufficient evidence that the tests used APRI and FIB-4 have the ability
to distinguish cirrhosis in this co-infected patients (F0-3 versus F4).
Conclusions
The performance validation of these diagnostic tests was not established yet for this group of HIV + HBV patients. This study is trying to
get the diagnostic criteria for liver disease in virus B co-infected HIV
BMC Infectious Diseases 2016, Volume 16 Suppl 3
patients, using available methods, non-invasive, reproducible. Will be
required large study trials to compare non-invasive methods with
liver biopsy or to discover new diagnostic scores, individualized for
these groups of patients.
P6
HIV late presenters in Craiova Regional Center, Romania
Florentina Dumitrescu1, Augustin Cupsa1, Andreea Cristina Stoian1,
Lucian Giubelan1, Irina Niculescu1, Iulian Diaconescu1, Dan Hurezeanu1,
Livia Dragonu1, Mioara Cotulbea2
1
Infectious Diseases Department, University of Medicine and Pharmacy
from Craiova, Craiova, Romania; 2“Dr. Victor Babeș” Hospital of Infectious
Diseases and Pneumology, Craiova, Romania
Correspondence: Florentina Dumitrescu (elenadumea@yahoo.com) –
Infectious Diseases Department, University of Medicine and Pharmacy
from Craiova, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P6
Background
Late presentation for HIV care remains a significant issue. The aim of
the study is to evaluate the proportion and the risk factors for late
HIV testing and presentation to care in the Craiova Regional Center
(CRC), Romania.
Methods
All patients newly HIV diagnosed in CRC between January 2010 and
December 2014 were included an initial CD4 count <350 cells/cmm
or an AIDS-defining illness within 6 months after diagnosis defined
late presenters (LP). Demographic, behavioral characteristics and biological data of LP were compared with those of non-late presenters
(NLP).
Results
Of 129 patients included, 79 (61.2 %) were LP. Characteristics of LP
vs NLP: male-46 (58.2 %) vs 20 (40 %), urban area-35 (44.3 %) vs 27
(54.0 %), heterosexual acquired HIV infection- 71 (89.8 %) average vs
43 (86 %), average age at HIV diagnosis-30.7 ± 10.1 years vs 26.2 ±
14.8 years, median CD4- 124 (IQR 1, 335) cells/cmm vs 607 (IQR 359,
3605) cells/cmm. LP were more likely to be older (p = 0.04), male (p
= 0.04), heterosexual (p = 0.01) and less likely to be highly educated
(p = 0.0001). LP were more likely to have the first HIV test following a
doctor recommendation (p = 0.001). NLP were tested for HIV after a
specific risk situation (p < 0.0001).
Conclusions
In CRC Romania, the proportion of LP was high. Older age, male, heterosexual acquired of HIV and low level of education showed a
higher risk of being diagnosed late. Better strategies for HIV testing
are needed.
P7
Some aspects of malignancies in patients HIV / AIDS
Simona Manuela Erscoiu1, Ionuț Cristian Popa2, Denisa Stroie2,
Petronela Ionescu2, Nedeea Duță2, Camelia Dobrea3, Irina Voican4,
Emanoil Ceaușu1, Petre Iacob Calistru1
1
Carol Davila University of General Medicine and Pharmacy Bucharest,
Bucharest, Romania; 2Clinical Hospital for Infectious and Tropical
Diseases “Dr. Victor Babeș” Bucharest, Bucharest, Romania; 3Monza
Hospital, Bucharest, Romania; 4Bucharest University Emergency Hospital,
Bucharest, Romania
Correspondence: Simona Manuela Erscoiu (serscoiu@yahoo.com) –
Carol Davila University of General Medicine and Pharmacy Bucharest,
Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P7
Background
Although 20 years have passed since the initiation of HAART which
has resulted in increased survival time and improved quality of life of
patients infected with HIV, they are at higher risk of developing certain cancers such as Kaposi sarcoma (KS), non-Hodgkin lymphoma
(NHL), and cervical cancer. Unfortunately, in recent years malignancies have increased in number to the entire population of the globe.
Page 18 of 29
The connection between HIV/AIDS and certain cancers is not completely understood, but the link likely depends on a weakened immune system. The incidence of KS and NHL has decreased markedly,
but there has been a relative increase in tumor types that collectively
are referred to as non-AIDS-defining cancers (NADCs) compared with
the general population. NADCs now are a major factor contributing
to mortality in HIV-infected people.
Methods
Retrospective, observational, descriptive study. Data were collected
from January 1990 to December 2015 from patients admitted in Casa
Andreea department. We included only patients in whom diagnostic
criteria for malignancy were confirmed. If in the 90s, diagnosis and
therapy were difficult, in last 5 years etiological and therapy possibilities have improved. Explored imaging cases, histological and immunohistochemistry examinations were done, the consequence being
targeted chemotherapy.
Results
We analyzed 72 patients, 83 % being heterosexually HIV infected
men. The median age was 39 years. 40 % of patients HIV had malignancies while only 20.34 % of them had been diagnosed with malignancy before HIV seropositivity. The rest had a range between
3 months and 10 years to malignancy diagnosis HIV viral load had a
median of 570 000 c/mL and the CD4 cell count was below 200 lymphocytes /cmm at the cancer diagnosis (40.28 %). Immunohistochemistry was made in 42 % patients. Malignancy were NHL 28 %,
KS 11 %, 10 % lung cancer, skin carcinoma 11 %, digestive cancer
11 %, 7 % cerebral lymphoma. At the time of diagnosis 58 % had
already metastasized neoplasia. Radiotherapy received 24 %, 42 %
had repeated courses of chemotherapy. HAART received 82 % of patients and at the end of the study 31.95 % had undetectable viral
load. However the death toll was 71 %, 79 % died in the same year
of malignancy diagnosis. Concomitant pulmonary TB had 34 % of
patients.
Conclusions
As patients live longer with HIV, morbidity and mortality from cancers are increasing. We must be able to quantify and characterize
cancers in HIV. Treatment of malignancies in HIV should be vigorous
and appropriate to the situation.
P8
Factors associated with resilience among people living with HIV in
Romania
Florin Lazăr
Bucharest University, Bucharest, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P8
Background
Resilience, defined as the ability to adapt to new circumstances, is
one of the major aims in the cascade of care of people living with
HIV (PLHIV), presumably ensuring an independent, reliable partner
during the management of the infection. The aim of the study is to
identify factors associated with resilience of PLHIV in Romania.
Methods
A cross-sectional survey using a self-reported questionnaire was carried out between November 2014 and March 2015 among 252 adult
PLHIV aware of their status for at least 6 months. A global score of
resilience representing the dependent variable was derived from Resilience Scale for Adults (RSA, alpha = 0.943) created by Friborg et al.
(2003, 2005) based on 33 pairs of situations/items with responses
using semantic differential (five points) grouped into four subscales
(personal strengths, family, relationships, social resources). Validated
measures of quality of life (alpha = 0.934), coping (alpha = 0.843), depression (alpha = 0.946), HIV Stigma Scale (alpha = 0.943), were tested
for association with RSA. Independent variables were subscales from
the above-mentioned scales accompanied by variables on social support (no. of close relatives and friends to talk to), importance of God
and adherence (no. of days of treatment interruptions in the last four
weeks). A linear multivariate regression was performed (adjusted r
square of the final model was: 0.841) to identify factors associated
with resilience.
BMC Infectious Diseases 2016, Volume 16 Suppl 3
Page 19 of 29
Results
The most important predictors of resilience are: not having lost interest in life (subscale from the depression scale) (ß CI95%: -0.499
[-7.228 - -4.140], p < 0.000), having a better quality of life, domain environment (ß CI95%: 0.338 [1.962- 4.845], p < 0.000), having more
social support from family and friends (ß CI95%: 0.220 [0.365- 1.478],
p < 0.002), having interrupted treatment less in the previous four weeks
(ß CI95%: -0.207 [-3.145 - -0.752], p < 0.002) and considering God less
important in life (ß CI95%: -0.184 [-2.686 - -0.528], p < 0.004).
Conclusion
PLHIV who are resilient have not given-up, receive more social support, live in a better environment (having a better quality of life) are
more adherent to treatment, but do not rely on religion/God, being
in control over their life. In building resilience in their patients professionals need to pay special attention to maintaining hope, enhancing
social support, ensure access to a qualitative living environment and
encourage PLHIV not to let their life in “God Will”, which in turn can
have a positive impact on adherence.
the written consent is available for review by the Editor of this
journal.
P9
Fever in HIV-infected patients: a thorny problem to be solved by
the clinicians
Lucian Giubelan1,2, Augustin Cupșa1,2, Iulian Diaconescu1,2, Florentina
Dumitrescu1,2, Dan Hurezeanu1,2, Livia Dragonu1,2, Irina Niculescu1,2,
Andreea Cristina Stoian1,2, Oana Obretin2, Mariana Stănescu2, Mihai
Jianu2
1
University of Medicine and Pharmacy, Craiova, Romania; 2Victor Babeș
Hospital of Infectious Diseases and Pneumology, Craiova, Romania
Correspondence: Lucian Giubelan (ligiubelan@yahoo.com) – Victor
Babeș Hospital of Infectious Diseases and Pneumology, Craiova, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P9
Background
The study is a retrospective analysis of cytokines expression on both
gene and protein levels in HIV-infected individuals receiving clinical
care at the Croatian Reference Center for HIV/AIDS of the University
Hospital for Infectious Diseases (UHID) in Zagreb, Croatia.
Methods
Thirty four patients were enrolled for cytokine expression analysis on
protein level in acute and chronic phase of HIV-1 infection. The expression of 84 cytokine genes was measured in 3 patients in acute
and 3 patients in chronic phase of HIV-1 infection using PCR array
technology. To measure the concentrations of Th1/Th2/Th9/Th17/
Th22 cytokines, bead-based cytometry was applied.
Results
The results showed statistically significant increase of 13 cytokine
gene expression (cd40lg, csf2, ifna5, il12b, il1b, il20, lta, osm, spp1,
tgfa, tnfsf 11, 14 and 8) and downregulation of the il12a expression
in chronic HIV-1 infection. Concentrations of IL-10, IL-4 and TNF-α
were increased in the acute HIV-1 infection when compared to the
control group. During chronic HIV-1 infection there was an increase
of IL-10, TNF- α, IL-2, IL-6, IL-13 and IL-22 levels when compared to
the control group. Comparison of cytokine expression between two
stages of infection showed significant decrease in IL-9 concentration.
Conclusion
In this study we showed the existence of cytokine profile change on
both gene and protein levels as the HIV-1 infection progresses from
acute to chronic stage. There was no Th1 to Th2 cytokine switch between these two stages of infection. In chronic HIV-1 infection 13
genes encoding different cytokines were overexpressed indicating
the hyperactivation of the immune system. Among HIV-infected individuals during chronic infection concentrations of IL-9 were significantly reduced when compared to the acute stage of infection. The
hyperactivation of the immune system is present even during
chronic HIV-1 infection with sustained viral replication.
Background
Fever in HIV-infected patients poses many problems to the clinicians,
forcing them to differentiate between the many possible causes (opportunistic infections, HIV itself, malignancies, various non-infectious
causes).
Case report
We present the case of a male patient, 53 years old, from Craiova, admitted in our department in November 2015 for isolated fever (max.
40 °C, lasting for the last three weeks before admission). He did not
consult his general practitioner, but he self-administered amoxicillinclavulanate and non-steroidal anti-inflammatory drugs, 7 days before
hospitalization. He was diagnosed with shingles 3 years ago; also he
has lost 13 kilograms in weight in the last year. On physical examination he appeared well despite high fever, having generalised paleness, laterocervical lymph nodes enlargement, oral thrush and
tachycardia (98/minute). Hematologic exploration revealed anemia
(8.8 g/dL), normal leukocyte counts (5540/cmm) with lymphomonocytosis (43.7 %) and elevated erythrocyte sedimentation rate
(115 mm/1 hour). Chest X-ray demonstrated a mediastinal widening
and disseminated micro-opacities. A CT scan confirmed the presence
of a tumoral mediastinal mass extending to the right thyroid lobe
and strangulating the right subclavian artery. ELISA and Western blot
tests for HIV were positive and further exploration showed at baseline a viral load of 574000 copies/mL and a CD4 count of 128 cells/
cmm. He started antibacillary treatment (based on a presumptive
diagnosis of tuberculosis) and, two weeks later, antiretroviral treatment with Abacavir, Lamivudine and Enfuvirtide. Under treatment
fever resolved, but, two months later, reappeared after immune reconstitution (CD4 count 392 cells/cmm), imposing corticosteroid therapy. Currently, tests for diagnosis of malignancy are undergoing
(non-Hodgkin lymphoma being suspected).
Conclusion
Fever in HIV-infected patients might be a thorny problem for the clinicians; based on epidemiological and statistical data, antibacillary
treatment might be the starting point for solving this matter.
Consent
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of
P10
Th1, Th2, Th9, Th17 and Th22 cytokines in acute and chronic HIV-1
infection
Lana Gorenec1, Snjezana Zidovec Lepej1, Ivana Grgic1, Ana Planinic1,
Janja Iscic Bes1, Adriana Vince2, Josip Begovac3
1
Department of Molecular Diagnostics and Flow Cytometry, University
Hospital for Infectious Diseases Zagreb, Zagreb, Croatia; 2Department of
Viral Hepatitis University Hospital for Infectious Diseases Zagreb, and
University of Zagreb, School of Medicine, Zagreb, Croatia; 3Department
of HIV/AIDS, University Hospital for Infectious Diseases Zagreb, and
University of Zagreb, School of Medicine, Zagreb, Croatia
Correspondence: Snjezana Zidovec Lepej (szidovec@gmail.com) –
Department of Molecular Diagnostics and Flow Cytometry, University
Hospital for Infectious Diseases Zagreb, Zagreb, Croatia
BMC Infectious Diseases 2016, 16(Suppl 3):P10
Acknowledgments
This research was funded by the Croatian science foundation project titled
“Molecular, epidemiological and clinical features of HIV infection in Croatia”
(principal investigator Prof. Josip Begovac).
P11
Dyslipidemia in HIV-infected patients treated with protease
inhibitors – case report
Luminița Elena Horga
Infectious Diseases Hospital Cluj-Napoca, Cluj-Napoca, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P11
Background
People with HIV infection are getting older, thus they could have comorbidities associated with aged persons, like dyslipidemia. The
treatment for the HIV infected patient who has also metabolic
BMC Infectious Diseases 2016, Volume 16 Suppl 3
Page 20 of 29
abnormalities is a challenge for all health care workers involved.
Goals of therapy include promoting long-term adherence, avoiding
drug interactions, minimizing toxic effects. The main objective of
this presentation was to assess the impact of clinical pharmacist
with significant issues related to the use of antiretroviral therapy
(ART) and lipid lowering agents in patients with HIV infection and
dyslipidemia.
Case report
We analyzed significant pharmacokinetic drug-drug interactions between statin and ART, the additive toxicities associated with concomitant ART and statin drug use.
A 47-year-old white male, light smoker, nondrug user, was confirmed
with HIV infection stage B3 in 2013; his CD4 cell number was 2/cmm
and presented elevated creatinine. He started antiretroviral treatment
(ART) with abacavir, atazanavir and ritonavir, well tolerated. Clinical,
immunological and virological evolution was very good. One year
after starting ART triglyceride values reached 2322 mg / dL. Recommended by the nutritionist, fibrates (fenofibrate) and statins (rosuvastatin) regimen was introduced for lowering triglycerides. The
pharmacist intervention was to reviewing the medication, screening
for toxicity and drug-drug interactions, proper use of statin. Rosuvastatin increases the risk of myopathy and rhabdomyolysis associated
with fenofibrates. If association is absolutely necessary, rosuvastatin
daily dose should not exceed 10 mg. Concomitant administration of
atazanavir/ritonavir and rosuvastatin may increase plasma concentrations of rosuvastatin- increasing the risk of rhabdomyolysis. If is required, it is recommended to administer the lowest concentrations
of rosuvastatin. The dose of rosuvastatin was decreased from 20 to
10 mg. But in this situation the best regimen should be fenofibrate
and fluvastatin because there are no interactions.
Conclusions
One of the duties of the clinical pharmacist is “to consult with the
patient’s physicians and other health care providers in selecting the
medication therapy that best meets the patient’s needs and contributes effectively to the overall therapy goals” (AACP).
Consent
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy
of the written consent is available for review by the Editor of this
journal.
values for total cholesterol, LDL-cholesterol, triglycerides and total
lipids were considered up to 220, 150, 200, 750 mg/dL.
Results
In the Cluj Regional Centre at the end of December 2015 were
followed 446 patients; 370 were under antiretroviral therapy (ART).
Above 50 years old there were 66 patients. We selected 60 patients,
59 with ART. Average age was 57 (54.7 for females). 19 were females,
in menopause. The number of patients with comorbidities was: 16
gastrointestinal, 14 cardiovascular, 4 with active TB, 1 with diabetes.
17 of 60 were with intercurrences. 32 out of 60 (52 %) had dyslipidemia (12 women, 37.5 %): 11 with mixed dyslipidemia, 14 with
hypercholesterolemia, 7 with hypertriglyceridemia. Average values
for total cholesterol, LDL-cholesterol, triglycerides and total lipids
were 250, 187, 303 and 923 mg/dL. Average CD4 cell count value
was 503/cmm. Daily dose of medicines was 5.8 for HIV, TB and
chronic comorbidities and 6.8 if adding the intercurrences. Only 4 patients (12 %) from 32 with dyslipidemia were on lipid-lowering drugs.
Conclusion
There is an important burden using many drugs in HIV infected
adults above 50. Daily average of medicines is 5.8 and increases at
6.8 in case of intercurrences. The priority is represented by ART and
drugs for acute comorbidities (like tuberculosis), drugs for chronic comorbidities and, unfortunately, least for dyslipidemia. There is a need
for initiating treatment for dyslipidemia, if the life style is changed
and dyslipidemia persists. Polypharmacy might be an obstacle in prescribing lipid-lowering medication.
P12
Why is less treatment used for the metabolic abnormalities in HIV
patients-too many drugs?
Corina Itu1, Luminița Elena Horga1, Laura Augusta David-Aldea1, Anca
Ciorogar1, Cristian Jianu1, Mihaela Lupșe2
1
Clinical Hospital for Infectious Diseases, Cluj-Napoca, Romania; 2Iuliu
Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
Correspondence: Corina Itu (corinaitu@yahoo.com) – Clinical Hospital
for Infectious Diseases, Cluj-Napoca, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P12
Background
Patients with HIV/AIDS due to immunosuppression may develop repeated episodes of Herpes Zoster. We report a clinical case of HIV
late presenter associated with sacral Herpes Zoster with a hyperalgesic form with favorable evolution.
Case report
The authors present the case of a patient of 35 years, known as a
HIV late presenter, with mental retardation, esophageal candidiasis
and gallstones, who was hospitalized in the Clinic of Infectious Diseases Timisoara for fever (T = 39 °C), maculo-papular-vezicular rash
metameric (S1-S5) disposed, with burning sensation and sharp pain,
sacral eschar, marked asthenia. The onset is acute two days before
hospitalization with chills, malaise, painful skin rash with blisters involving the sacral area. The diagnosis was based on the clinical
symptoms associated with biological samples (number of leukocytes,
erythrocyte sediment ratio (ESR), C reactive protein (CRP), serum glucose, blood culture, CD4, viral load (VL), sacral wound secretion culture, etc.) and the results of paraclinical investigations (chest
radiography). During hospitalization, the patient received treatment
with: acyclovir 400 mg, 5x2 cp/day, sulfamethoxazole/trimethoprim,
2x2 cp/day, ceftriaxone 1 g, 2x2 g/day, fluconazole 200 mg, 1cp/day,
Perfalgan 100 mL 1 fl/day when required, Arnetin f, 1 f/day, infusion solutions with NaCl 0.9 % 500 mL 1 fl/day, Ringer Solution 500 mL 1 fl/
day, blood transfusion 1 U/day, plasma transfusion 1 U/day, nonsteroids anti-inflammatory (NSAIDS), Algifen 1f/day if needed, etc.
We mention the following lab results: leukopenia (3330/μL), increased ESR (130 mm/1st hour), CRP = 82.04 mg/L, Hb = 7.9 g/dL,
platelet (49000/ μL), sideremia (16 pg/dL), total protein (4.93 g/dL),
Background
The etiology of dyslipidemia in HIV infected patients is multifactorial
and its treatment is crucial in preventing cardiovascular disease. The
life style changes are mandatory followed by medication. The lipidlowering agents are similar to those used in general population, but
polypharmacy (more than 5 daily), drug-drug interactions and adverse reactions are more frequent. Some studies showed that the
use of lipid-lowering drugs remains lower in HIV infected adults than
in the general population.
Methods
We conducted a cross sectional study during 2015 in HIV infected
adults aged above 50, from The Regional AIDS Centre Cluj. The objective was to identify metabolic abnormalities, lipid-lowering treatment and associated medications. We analyzed the parameters: age,
gender, comorbidities, lipid profile, CD4 cell number; also the number of concomitant HIV drugs, tuberculosis (TB) drugs and drugs for
other comorbidities, patients in lipid-lowering treatment. Normal
P13
Sacral Herpes Zoster, with hyperalgesic form, in a patient with C3
stage HIV infection
Iuliana Caramangiu1, Ovidiu Roșca2, Monica Cialma2, Andreea
Ardeleanu1, Iosif Marincu2
1
Department of Infection Diseases I, “Victor Babeș” Clinical Hospital of
Infectious Diseases Timișoara, Timișoara, Romania; 2Department of
Infection Diseases I, University of Medicine and Pharmacy “Victor Babeș”
Timișoara, Timișoara, Romania
Correspondence: Iuliana Caramangiu (balteanu.iuliana@yahoo.com) –
Department of Infection Diseases I, “Victor Babeș” Clinical Hospital of
Infectious Diseases Timișoara, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P13
BMC Infectious Diseases 2016, Volume 16 Suppl 3
CD4 = 15 cells/μL, VL = 457825 copies/mL; blood culture = the absence of microbial growth; urine culture, present Escherichia coli
100.000 CFU/mL; wound secretion culture present Staphylococcus
aureus meticilino rezistent and Acinetobacter baumannii, with sensitivity to ceftriaxone, amikacin and sulfamethoxazole/trimethoprim.
Under treatment with antibiotics, antivirals, analgesics, NSAIDs, infusion solutions and antipyretics, the eruption continued the evolutionary cycle, but the pain persisted throughout the affected dermatomes
(S1-S5). It was established antiretroviral treatment with: TDF 1/day +
FTC 1/day + RAL 2x1/day. There were no reported adverse drug reactions, and patient showed good adherence to treatment.
Conclusions
Severe immunosuppression during HIV infection in C3 stage may
favor the occurrence of infections with Herpes Zoster. Clinical, biological and therapeutical monitoring are required for early diagnosis
of opportunistic infections in patients with HIV/AIDS and the establishment of appropriate therapy.
Consent
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the
written consent is available for review by the Editor of this journal.
P14
Factors associated with in-hospital mortality in tuberculous and
cryptococcal meningitis
Raluca Jipa1, Eliza Manea1, Șerban Benea1,2, Irina Lăpădat1, Nicoleta
Irimescu1, Irina Panait1, Cristian Niculae1, Adriana Hristea1,2
1
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest,
Romania; 2Carol Davila University of Medicine and Pharmacy, Bucharest,
Romania
Correspondence: Raluca Jipa (ralucajipa@yahoo.com) – National
Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P14
Background
Mycobacterium tuberculosis and Cryptococcus spp. are the most frequent etiologies of meningitis in HIV infected patients. Both tuberculous meningitis (TBM) and cryptococcal meningitis (CM) are
associated with high risk of mortality, especially in HIV infected
patients. We assessed the risk factors for in-hospital mortality in
HIV infected patients with TBM and CM.
Methods
Retrospective study between January 2006 and December 2015. We
included HIV infected patients diagnosed with TBM and CM. Hospital
records were reviewed and data on patient history, epidemiological
characteristics, clinical findings including neurological examination,
cerebrospinal fluid (CSF) changes and cerebral imaging were analyzed. Patients were defined as having TBM according to a consensus
definition published by Marais et al.; CM diagnosis was established
upon positive India ink stain, culture and/or cryptococcal antigen
assay. Neurological staging was made according to Medical Research
Council definitions.
Results
We identified 41 HIV infected patients with TBM (26 definite, 12
probable and 3 possible) and 42 with CM. Fifteen (37 %) patients
with TBM died compared to 17 (41 %) patients with CM. Nine patients (60 %) with definite TBM and 6 (40 %) with probable TBM died.
No statistically significant differences were observed between patients with TBM and CM regarding demographic and clinical data except duration of symptoms before admission, 14 (9-15) days in
patients with TBM vs. 4 (3-6) in patients with CM (p < 0.001) and CD4
cell count, 68 (20-145) cells/cmm in patients with TBM vs 13 (8-38)
cells/cmm in patients with CM (p = 0.002). Most of the patients had
severe neurological involvement (stages 2 and 3): 14 (93 %) patients
with TBM vs 16 (94 %) patients with CM (p = 1, OR [95 % CI] = 1.1
[0.06-20]). A higher CSF protein level and number of cells per µL
were observed in patients with TBM vs patients with CM, 230
(118-778) mg/dl in patients with TBM vs 58 (45-129) in patients
with CM (p = 0.006), respectively 200 (9-1406) cells per µL in patients with TBM vs 60 (25-106) cells per µL in patients with CM
Page 21 of 29
(p = 0.013). Hydrocephalus was more frequent in patients with
CM (41 %) than in patients with TBM (20 %) (p = 0.6, OR [95 %
CI] =1.7[0.2-13.1]).
Conclusion
Patients diagnosed with TBM and CM were severely immunosuppressed and had a similar neurological involvement and high inhospital mortality. Demographic and clinical data were similar in patients who died within the two groups. Patients with TBM who died
had higher protein levels and numbers of cells per μL in the CSF vs
those with CM.
P15
Lipodystrophy: still present adverse event in resource-limited
settings
Jovana Kusic1, Djordje Jevtovic1, Dubravka Salemovic1, Jovan Ranin1,
Bozana Dimitrijevic2, Gordana Dragovic2
1
The HIV-AIDS Center, Institute of Infectious and Tropical Disease ‘Dr
Kosta Todorovic’, School of Medicine, University of Belgrade, Belgrade,
Serbia; 2Department for Pharmacology, Clinical Pharmacology and
Toxicology, School of Medicine, University of Belgrade, Belgrade, Serbia
Correspondence: Jovana Kusic (jovanakusic@yahoo.com) – The HIVAIDS Center, Institute of Infectious and Tropical Disease ‘Dr Kosta
Todorovic’, School of Medicine, University of Belgrade, Belgrade, Serbia
BMC Infectious Diseases 2016, 16(Suppl 3):P15
Background
Highly active antiretroviral therapy (HAART) has led to dramatic reductions in mortality and morbidity of HIV-infected patients. Lipodystrophy, a syndrome with peripheral fat wasting and central obesity,
is a well-documented side effect of old antiretroviral drugs, still prescribed as the first line regimen in resource-limited settings. The aim
of this study was to evaluate the incidence of lipodystrophy and to
determine its risk ratios in HIV-infected patients in a resource-limited
setting.
Methods
This cross-sectional study included all the antiretroviral-naive HIVinfected patients commencing HAART from 1st January 2001 to 31st
December 2013, at the HIV/AIDS Center, Institute of Infectious and
Tropical Diseases, Belgrade, Serbia. Univariate and stepwise multivariate logistic regression analyses were used to determine the odds
ratios (OR) with the confidence interval (CI) of 95 %, in order to establish the relative risk for development of lipodystrophy. The
Kaplan-Meier-method was used to determine the probability of development lipodystrophy over time. All statistical analyses were performed using SPSS software version using 0.05 as a p-threshold for
the significance.
Results
This study included 955 HIV/AIDS patients, 683 men and 272 women,
followed for 8.6 ± 3.8 years. The prevalence of lipodystrophy was
64.9 %. Univariate and stepwise multivariate regression analysis identified that the female gender, hepatitis C virus co-infection, AIDS
diagnosis prior to HAART initiation, nucleoside-reverse-transcriptaseinhibitors and protease-inhibitors based regimens had a high risk for
developing lipodystrophy in HIV-infected patients (OR = 1.9, 95 % CI
= 1.2-3.67, p = 0.04; OR = 3.97, 95 % CI = 1.1-7.1, p < 0.01; OR = 3.9,
95 % CI = 1.2-6.9, p < 0.01; OR = 2.9, 95 % CI = 1.4-3.8, p < 0.01; OR =
6.6, 95 % CI = 4.8-9.1, p < 0.01, respectively).
Conclusion
Despite much greater life expectancy of HIV-infected patients,
treatment-related toxicities still remain a major concern. Lipodystrophy, as side effect of HAART, is particularly still important in
resource-limited settings.
P16
TB and HIV coinfected patient, an emergent challenge - case
report
Laura-Augusta Aldea-David
Infectious Diseases Hospital, Cluj-Napoca, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P16
BMC Infectious Diseases 2016, Volume 16 Suppl 3
Background
Concomitant therapy for HIV and tuberculosis leads to polypharmacy.
This fact might be a challenge for the physician, but also for the
pharmacist. The objective of this presentation was to evaluate the
impact of clinical pharmacists on important issues related to the use
of antiretroviral therapy (ART) in patients with active tuberculosis
disease.
We analyzed significant pharmacokinetic drug-drug interactions between antituberculous and antiretroviral treatment, the additive toxicities associated with concomitant ARV and TB drug use.
Case report
A 59-year-old white male nonsmoker, nondrug user, was confirmed
with HIV advanced disease in January 2015. His CD4 was 9 cells/
cmm. He was coinfected with disseminated tuberculosis, with lung,
liver and spleen involvement. He was with bilateral stents and suprapubic drainage. Associated he presented tracheobronchitis with Candida krusei and urinary tract infection with Klebsiella, Serratia and
Enterococcus. His medications include TB drugs, ART, antifungal and
antibiotics. Patient tolerated drugs well, had immunological and virological response to ART. During the treatment his CD4 cell number
increased to 104 cells/cmm, the viral load decreased and his clinical
evolution was good. We reduced the polypharmacy by reviewing the
medication, medication reconciliation, introduced treatment for opportunistic infections, screening for toxicity and drug interactions,
proper use of rifampicin-isoniazid: rifampicin is a potent enzyme inducer of the cytochrome P-450 isozymes (CYP3A4, CYP1A2, CYP2A6,
CYP2B6, CYP2C8/9, CYP2C19), leading to decreased serum concentrations of medications metabolized by that isoenzyme. Isoniazid is a
potent inhibitor of the cytochrome P-450 isoenzymes (CYP2C9,
CYP2C19, and CYP2E1) but has minimal effect on CYP3A, so the inductive effect of rifampicin outweighs the inhibitory effect of isoniazid. When used in conjunction with rifampicin, isoniazid dosage
>10 mg/kg daily may increase the incidence of hepatotoxicity. The
risk of hepatotoxicity is greater when rifampicin and isoniazid are
given concomitantly than when either drug is given alone, so we delayed for 30 minutes the administration time between the two drugs;
they must be taken on an empty stomach. We administrated Pyridoxine (vitamin B6) 25-50 mg daily to reduce the occurrence of
isoniazid-induced side effects in the central and peripheral nervous
system.
Conclusions
A high percentage of pharmacists’ recommendations were accepted
by the physician, the majority of the pharmacist’s functions involved
ART dosing, detection of drug interactions or adverse drug reactions,
provision of drug information, ART adherence counseling. With the
growing number of HIV-positive individuals worldwide, the clinical
pharmacist may have a place in the multidisciplinary team, providing
care in people life.
Consent
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of
the written consent is available for review by the Editor of this
journal.
P17
Efficacy of prophylactic antiretroviral treatment in new-born
infants from HIV-positive mothers in 2012-2014, for the NorthEastern part of Romania
Carmen Manciuc1,2, Cristina Nicolau1, Liviu Prisăcariu1, Alexandra Largu1,2
1
“Sf. Parascheva” Infectious Diseases Clinical Hospital, Iași, Romania;
2
“Gr. T. Popa” University of Medicine and Pharmacy, Iași, Romania
Correspondence: Cristina Nicolau (crinic2004@yahoo.com) –
“Sf. Parascheva” Infectious Diseases Clinical Hospital, Iași, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P17
Background
In the North-Eastern region of Romania most of the female HIVpositive population are sexually active and at child bearing age. In
Romania there is a strict protocol regarding HIV vertical transmission.
Page 22 of 29
We aim to evaluate the efficiency of this protocol and the degree of
appliance, reflected in the HIV status of new-born infants from HIVpositive mothers for a period of 3 years.
Methods
Of the 1424 patients actively monitored in the HIV/AIDS Regional
Center in Iași, Romania, 46.5 % (663) are female. We evaluated retrospectively the files of all new-born infants from HIV-positive mothers
for a period of 3 years (January 2012 - December 2014).
Results
In the period mentioned above, 100 children were born (36 in 2012,
38 in 2013, 26 in 2014); one death occurred 10 days after birth, due
to multiple organ malformations; the lowest weight at birth was
750 g; 3 of the children (3 %) had a detectable viral load at birth; in
one case we could not evaluate the viral load; 98 children (98 %)
were born through caesarian section; 2 were born through natural
labor (2 %), one of which at home. Mothers received treatment with
lopinavir/ritonavir + zidovudine/lamivudine through the whole pregnancy in 81 cases; in 8 cases the mothers did not receive any treatment, being tested for HIV at birth. For all newborns prophylaxis was
made with zidovudine + lamivudine for 6 weeks. Three children
remained positive at 18 months, and therapy for them consisted in
zidovudine + lamivudine + nevirapine.
Conclusions
Evaluation of pregnant HIV-positive women and prophylaxis for newborn infants in the evaluated period were conducted according to
protocols, which resulted in a small percentage of HIV-positive children (3 %).
P18
Surveillance of mother to child transmission of HIV in Romania –
31 December 2015
Mariana Mărdărescu1,2, Adrian Streinu-Cercel1,2, Cristina Petre1, Marieta
Iancu2, Sanda Vintilă2, Daniela Vitelaru2, Iosif Ionel3, Claudiu Mihai
Șchiopu1, Alexandra-Henriette Mărdărescu1
1
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest,
Romania; 2Compartment for Monitoring and Evaluation of HIV/AIDS
Data in Romania, Bucharest, Romania; 3National Institute for Public
Health, Romania-National Centre for Surveillance and Control of
Transmissible Diseases, Bucharest, Romania
Correspondence: Mariana Mărdărescu (mardarescum@yahoo.com) –
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest,
Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P18
Background
The UNAIDS Report for 2015 revealed that out of a total of 36.9 million PLWHA (people living with HIV/AIDS) 17.4 million women were
infected with HIV. The same statistics showed that out of approximately 5600 new cases of HIV infections daily, 600 were pediatric HIV
new cases, with ages below 15 years, while around 5000 were adults
over 15, 48 % of them being women. 73 % of pregnant women living with HIV/AIDS had access to antiretroviral treatment in 2014. In
Romania statistics at 31 December 2015 for the period 1985-2015,
showed that out of 13.766 PLWHA and registered in the national
database, 5802 were women (48 %). Women at their fertile age (1529 years) accounted for 3358 cases (42 %). At the same time, 211
(1.53 %) cases were reported in children through materno-fetal transmission (starting with 1990).
Methods
The National Registry of materno-fetal transmission of HIV collects
and analyses data on mothers and their exposed infants from the
nine Regional HIV Centers in Romania. For the mothers the focus falls
on: time of HIV diagnosis, medical history, risk factors, disease and
therapeutic history, immunological and virological investigations. Regarding their children, the assessment concentrates on risk factors
such as type of birth, the newborn’s postpartum ART, type of feeding
and ART during pregnancy. Furthermore, they undergo virological
and immunological baseline investigations, and at 6 and 18 months
of surveillance.
BMC Infectious Diseases 2016, Volume 16 Suppl 3
Results
During 01.01.2013-31.12.2015, we registered 568 mothers and children. 36 % of mothers belong to the 1987-1990 cohort, 35 % are
cases with HIV sexual transmission who are already in surveillance
and another 10 % are sexual and IDU (injecting drug use) transmission cases as well as late presenters in the sanitary system. From the
overall female patients registered, 437 (77 %) were under ante- and
intra-partum treatment and 460 (81 %) had a Cesarean section.
Among infants with maternal exposure to HIV, 535 (94 %) received
post-partum prophylaxis. 512 infants (90 %) underwent virological
assay during the first 72 hours after birth. In terms of feeding, 540
(95 %) received formula. Early infant diagnosis revealed that 5 % of
the assessed children were HIV infected.
Conclusion
Taking into consideration 4 essential risk factors that determine the
status of infants to HIV positive mothers and by applying logistical
regression we concluded that the mother’s treatment during pregnancy and the newborn’s postpartum ART represent risk factors with
a significant impact on the infant’s status at birth (p value = 0.019
and p-value = 0.0001).
P19
The antiretroviral therapy failure and the need to select the
effective treatment in the Republic of Moldova
Pavel Micsanschi1, Tiberiu Holban1, Ina Bîstrițchi1, Lucia Pârțână2, Angela
Nagîț2, Svetlana Popovici2, Maria Talmaci2, Irina Cucerova2
1
Department of Infectious Diseases, Parasitology and Tropical Medicine,
Nicolae Testemițanu State Medical and Pharmacy University, Chișinău,
Republic of Moldova; 2Hospital of Dermatology and Communicable
Diseases, Chișinău, Republic of Moldova
Correspondence: Pavel Micsanschi (micsanschipavel@yahoo.com) –
Department of Infectious Diseases, Parasitology and Tropical Medicine,
Nicolae Testemițanu State Medical and Pharmacy University, Chișinău,
Republic of Moldova
BMC Infectious Diseases 2016, 16(Suppl 3):P19
Background
We observed a continuous recording of new cases of first-line antiretroviral treatment failure that have led to the need to select the individual second-line antiretroviral therapy for the HIV-infected
patients with therapeutic failure. The major facts which cause ARV
failure are poor adherence, inadequate drug levels or prior existing
drug resistance.
Methods
In this study we followed-up 45 patients who corresponded by immunological and clinical criteria for first line antiretroviral treatment
failure (AZT + 3TC + EFV/ d4T + 3TC + NVP/ AZT + 3TC + NVP/ ABC +
3TC + EFV/ (TDF + FTC) + NVP/ ABC + 3TC + NVP/ (TDF + 3TC + EFV)/
(TDF + FTC) + EFV/ (TDF + 3TC) + NVP) and started the second-line
therapy in 2011-2015. Included patients were aged between 23-69
years (38.4 ± 0.3 years). After first-line antiretroviral therapy failure
(HIV RNA viral load measurement >400 copies/mL after 5 months)
switching to a new second line regimen became necessary.
Results
All 45 patients who were confirmed with failure of first-line antiretroviral therapy started the second-line regimens of HAART. At the setting of first-line antiretroviral therapy failure approximately 2/3 of
patients had viral load >100000 copies/mL. From the individuals included in the study who have been defined with the failing to the
therapy, 38 patients were detected with CD4 counts <350 cells/cmm,
out of which 25 patients were detected with CD4 counts <200 cells/
cmm and 9 patients of them were detected with CD4 counts <50
cells/cmm that is associated with increased risk for morbidity or
death. After 6 months from initiation of second-line antiretroviral
treatment 41 patients had HIV RNA <25 copies/mL, three of them
responded more difficult to treatment, but one patient had not
responded to the therapy and maintained viral load >100000 copies/
mL and was detected with CD4 counts <200 cells/cmm. The duration
from initiation of first-line antiretroviral treatment until failure of it
Page 23 of 29
and initiation of second-line antiretroviral therapy was also significantly different for each patient but the median time was 4.13 years
(interquartile range: 1-10 years).
Conclusion
Due to detecting early first-line treatment failure and initiation the
second-line therapy in the majority of patients who had viral load
>100000 copies/mL and the average CD4 cell count was 205.4 cells/
cmm, antiretroviral treatment was successful. Our study outcomes
support the need for early identification of first-line treatment failure
because a delay in switching therapy in patients with high level of
viral replication may lead to greater development of resistance and
compromise the virological activity of second-line regimens.
P20
Disseminated cryptococcosis in a patient with C3 HIV stage and
multiresistant to antiretroviral therapy with lethal evolution
Sorina Georgiana Mitrescu1, Dana Mihalcea1, Iulia Caramangiu1,
Ovidiu Roșca2, Iosif Marincu2
1
Department of Infection Diseases I, “Victor Babeș” Clinical Hospital of
Infectious Diseases Timișoara, Timișoara, Romania; 2Department of
Infection Diseases I, University of Medicine and Pharmacy “Victor Babeș”
Timișoara, Timișoara, Romania
Correspondence: Sorina Georgiana Mitrescu (sorina.mitrescu@yahoo.ro) –
Department of Infection Diseases I, “Victor Babeș” Clinical Hospital of
Infectious Diseases Timișoara, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P20
Background
Cryptococcosis is a deadly opportunistic infection caused by an encapsulated yeast, Cryptococcus neoformans. The major predisposing
factor is the profound cellular immune defect caused by HIV infection. Cryptococcal meningitis is the most common life-threatening
fungal infection in patients with AIDS.
Case report
The authors present a clinical case of disseminated cryptococcosis in
a patient with HIV infection stage C3 with multiple ARV therapeutic
schemes from 2001 to 2014 and treatment failure. Clinical manifestations of infection associated with the diagnosis: lymphadenopathy
and recurrent oropharyngeal candidiasis, anemia, lingering pneumonitis, right pleural effusion, and hilari adenopathy, recurrent diarrhea, wasting syndrome, tuberculous pleurisy, HIV encephalopathy
seizure form, Toxoplasma chorioretinitis.
At first presentation in the clinic, the patient accuses fatigue, fever,
polymorphic eruption, sweating, left hemibody motor deficit, tachycardia, cough, abdominal pains, hematuria and headache. The positive diagnosis of cryptococcal sepsis and cryptococcal meningitis was
established based on following criteria: clinical (asthenia, fever and
stiff neck), biological (ESR, WBC, CD4, viral load, CSF viral load, blood
culture, CSF fungal culture), paraclinical (chest radiography, abdominal echography, cranial MRI).
We mention the following pathological results: ESR = 140 mm/h, CRP
= 33.52 mg/L, WBC = 1000 cells/μL, CD4 = 5 cells/μL, viral load =
323867 copies/mL, CSF viral load = 54359 copies/mL, blood culture =
Cryptococcus neoformans, CSF fungal culture = Cryptococcus neoformans. Paraclinical: chest radiography - right basal condensation block
with free pleural effusion, cranial MRI - supra tentorial gliotic lesions
probably of infectious origin. It was established medical therapy with
fluconazole 1200 mg/day, antibiotics, vitamins, antiepileptic, balancing solutions. We changed the Combivir and Viramune treatment
set from 2014, with Prezista 1200 mg/day, Norvir 200 mg/day, Intelence 400 mg/day and Isentress 800 mg/day. Under this treatment
the patient had improved general state but he developed an anxious
depressive syndrome and asked discharge against medical advice.
Adherence to ARV treatment was below 70 % with virological and
immunological failure despite more than 9 therapeutic regimens he
had from 2001 to 2014.
Conclusions
Patients with advanced HIV infection, non-adherent and uncooperative to ARV therapy may develop severe forms of disseminated
BMC Infectious Diseases 2016, Volume 16 Suppl 3
cryptococcosis with fatal outcome. Biological, therapeutical and clinical monitoring measures are required alonside individualized psychological counseling.
Consent
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of
the written consent is available for review by the Editor of this
journal.
P21
Aspects of tuberculosis infection in HIV-positive patients from
Romania – our experience
Anca Negru1,2, Daniela Munteanu1, Victoria Aramă1,2, Raluca Mihăilescu1,
Ioan Diaconu1, Remulus Catana1, Cristina Popescu1,2, Alina Orfanu1,2,
Anca Leuștean1, Mihaela Rădulescu1,2, Cătălin Tilișcan1,3, Raluca Năstase1,
Violeta Molagic1, Irina Duport1, Cristina Dragomirescu1, Ștefan Sorin
Aramă3
1
Adults 3 Department, National Institute for Infectious Diseases “Prof. Dr.
Matei Balș”, Bucharest, Romania; 2Infectious Diseases Department, Carol
Davila University of Medicine and Pharmacy, Bucharest, Romania;
3
Physiopathology and Immunology Department, Carol Davila University
of Medicine and Pharmacy, Bucharest, Romania
Correspondence: Anca Negru (anca1808@yahoo.com) – Adults 3
Department, National Institute for Infectious Diseases “Prof. Dr. Matei
Balș”, Bucharest, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P21
Background
Tuberculosis (TB) incidence in HIV infected patients is increasing especially in areas with high TB endemicity like Romania. Furthermore,
immunosuppression induced by the HIV infection changes the clinical presentation of TB, this group of patients presenting atypical
signs and symptoms, the extrapulmonary TB being more frequent.
Another aspect of TB infection is represented by the increase of multidrug resistant strains, leading to high morbidity and mortality.
Methods
We included into the study consecutive HIV infected patients diagnosed with tuberculosis in the Adults 3 Department of the National
Institute for Infectious Diseases “Prof. Dr. Matei Balș”, from January
until December 2015. TB diagnosis was established either through
sputum smears microscopy, positive blood cultures or protein chain
reaction (PCR) for Mycobacterium tuberculosis from pleural fluid, cerebrospinal fluid (CSF) or bronchial aspirate.
Results
We enrolled 13 patients with a median age of 33 (25; 38) years old,
seven of which had history of intravenous drug use. Median number
of CD4 cells at the time of TB diagnosis was 33 (15; 107) cells/cmm.
In six cases both infections were diagnosed at the same time. Regarding the symptoms, the majority of patients had prolonged fever,
without any respiratory symptoms, which persisted despite large
spectrum antibiotic treatment. Also the chest X-ray was not conclusive for TB. Five patients had pulmonary TB, five had systemic infection without clinical or radiological signs of pulmonary involvement
and three had both pulmonary and systemic TB. Out of those with
systemic TB 5 patients had hepatic and splenic abscesses identified
at ultrasound examination. In patients with systemic TB other sites of
infection included pericardium, pleura, peritoneum, kidney, lymph
nodes and central nervous system. In six cases the diagnosis was
established through sputum smear microscopy while three patients
had positive blood cultures. In the other cases the diagnosis was
established using Mycobacterium tuberculosis PCR from other biological fluids such as pleural fluid, bronchial aspirate and CSF. We isolated 2 resistant strains: one resistant to rifampin and the other one
to ethambutol and isoniazid. After initiation of anti-TB therapy two
patients developed toxic hepatitis, in one case the patient being coinfected with hepatitis C virus. Two patients had died during
hospitalization; none of them had resistant tuberculosis.
Conclusion
In HIV positive patients extrapulmonary TB is more frequent, this is
why the patient may present atypical symptoms, so this diagnosis
Page 24 of 29
must always be taken into consideration because early treatment decreases morbidity and mortality rates.
P22
Dyslipidemia in HIV-infected patients
Nicoleta M Negruț
Department of Neuroscience and Recovery, Faculty of Medicine and
Pharmacy, University of Oradea, Oradea, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P22
Background
Dyslipidemia is a common metabolic comorbidity in HIV-infected patients and may increase the risk for cardiovascular disease. According
to the World Health Organization ischemic heart disease will be the
leading cause of death in all countries by 2030. HIV-infected patients
have a high risk for cardiovascular disease due to toxicity from antiretroviral medications and uncontrolled HIV replication.
Methods
This retrospective study analyzed the lipid abnormalities mentioned
in the clinical database of all HIV-infected patients admitted in Hospital “Dr. Gavril Curteanu” Oradea, Romania, from January to December 2015. Dyslipidemia was classified according to the European
Atherosclerosis Society. The program IBM SPSS statistics version 22
was used for analysis of the dates.
Results
During 01.01-31.12.2015, a total of 42 files of HIV-infected patients,
were available for analysis. In the study group the lipid abnormalities
were found in 28 cases (66.67 %), hypercholesterolemia in 6 cases
(21.43 %), hypertriglyceridemia in 6 cases (21.43 %) and mixed hyperlipidemia in 16 cases (54.14 %). We found positive correlation between
the period of HIV infection and lipid values (Bravais-Pearson correlation
coefficient r = 0.33, p = 0.02). No correlation was found between age of
the patients and lipid values (Bravais-Pearson correlation coefficient r =
0.29, p = 0.058). Female patients developed hyperlipidemia in 11 cases
and males in 17 cases (p = 0.49, chi-square test).
Conclusion
In our study, 66.67 % of HIV-infected patients had lipid abnormalities.
Dyslipidemia was associated with HIV length infection, but not with
gender and age of the patient.
Acknowledgement
Financing of this study was supported by own sources.
P23
Challenges in the management of an HIV seropositive patient with
psoriasis undergoing immunomodulator therapy
Violeta Elena Niță1, Daniela Ioana Munteanu1, Raluca Mihăilescu1,
Ioan Diaconu1, Anca Negru1,2, Cristina Popescu1,2, Victoria Aramă1,2
1
National Institute for Infectious Disease “Prof. Dr. Matei Balș”, Bucharest,
Romania; 2Carol Davila University of Medicine and Pharmacy, Bucharest,
Romania
Correspondence: Violeta Elena Niță (violeta.nita@yahoo.com) –
National Institute for Infectious Disease “Prof. Dr. Matei Balș”, Bucharest,
Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P23
Background
Psoriasis is recognized as a systemic autoimmune inflammatory disease and the association between HIV and psoriasis represents a
challenge for the clinicians because both diseases have in the center
of the pathophysiology the T-lymphocyte. Frequently the autoimmune disease (AI) is refractory to treatment and moreover the
drugs themselves induce immunosuppression leading to increased
morbidity and mortality. Our aim is to present the management difficulties in the setting of immunological failure in a patient with HIV
and psoriasis.
Case report
A 34-year-old former intravenous drug user, with HCV chronic infection,
psoriasis vulgaris and psoriatic arthritis was diagnosed in December
BMC Infectious Diseases 2016, Volume 16 Suppl 3
2014 with HIV infection stage B3 (CD4 cell count 93 cells/cmm) and
started on combined antiretroviral therapy (cART)/DRV/r + 3TC + ABC.
Subsequently he was admitted into the hospital multiple times due to
worsening of the arthropathy. He was initiated on Sulfasalazine (SSZ)
and a low dose of corticosteroid (Prednisone 30 mg). But the lack of improvement imposed the increase of cortisone dose (Medrol 32 mg)
with slow tapering, and the replacement of ABC with AZT, the latter
having better results on AI. When cortisone was about to be stopped
the arthritis aggravated, requiring a prolonged period of therapy
(6 months). In this context the patient’s immunological status deteriorated (CD4 cell count 20 cells/cmm, August 2015), even though the
viral load was undetectable after 3 months of cART. The patient
returned to the hospital with a right crural zoster infection accompanied by VZV meningitis, responsive to IV acyclovir. Next, the patient was
diagnosed with left deep venous thrombosis which required sc anticoagulant therapy for 3 months. Because of drug-drug interactions
(DDI) between protease inhibitor (PI) and acenocoumarol, PI was
switched to an integrase inhibitor which induced toxic hepatitis. Therefore we resumed the PI and kept the sc anticoagulant therapy. One
month later the patient was diagnosed with pulmonary TB (on microbiological and imaging grounds). He was started on standard antituberculous therapy and the PI was replaced with Efavirenz due to DDI. The
patient’s AI deteriorated, needing multiple dermatological and rheumatologic consultations which recommended Methotrexate in place of
SSZ and further reduction of Medrol dosages.
Conclusions
Both HIV and the treatment for AI lead to poor immune status rendering this sort of patients susceptible to opportunistic infections.
ART should be selected cautiously in order to avoid DDI, and also the
deterioration of the AI. These patients have complex unpredictable
poly pathology, which brings supplementary challenges in their
management.
Consent
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of
the written consent is available for review by the Editor of this
journal.
P24
Acute peritonitis as a sign of IRIS in an HIV-infected patient with
MAC latent infection
Alina Orfanu1,2, Cristina Popescu1,2, Anca Leuștean1, Anca Negru1,2,
Remulus Catana1, Ioan Diaconu1, Cătălin Tilișcan1,2, Victoria Aramă1,2,
Sorin Ștefan Aramă2
1
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest,
Romania; 2Carol Davila University of Medicine and Pharmacy, Bucharest,
Romania
Correspondence: Alina Orfanu (alina.lobodan@yahoo.com) – National
Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P24
Background
Immune reconstruction inflammatory syndrome (IRIS) is a severe, lifethreatening complication in HIV-infected patients under antiretroviral
therapy (ART). Mycobacterium avium complex (MAC) is a common infection in immunosuppressed individuals (CD4 count < 50 cells/cmm)
which is often localized in the respiratory and gastro-intestinal tract.
HIV-infected patients are at high risk of MAC reactivation that can be
responsible for disseminated infection.
Case presentation
A 35-year-old patient was admitted to our clinic for prolonged febrile
syndrome associated with weight loss, diarrhea for one month, extreme odynophagia and laterocervical lymphadenopathy. At the clinical exam we found oral candidiasis, wasting syndrome, generalized
lymphadenopathy, hepatosplenomegaly. The laboratory tests confirmed stage-C3 HIV infection (CD4 count = 7 cells/cmm), with a viral
load of 120000 copies/ml. ART was initiated with CBV + LPV/r, with a
favorable outcome. Furthermore, Pneumocystis jiroveci pneumonia
(PCP) prophylaxis with trimethoprim/sulfamethoxazole and MAC
prophylaxis with clarithromycin were initiated. After two weeks, the
Page 25 of 29
patient developed high fever and severe abdominal pain, especially
in the right flank and iliac fossae, associated with signs of peritoneal
irritation. The laboratory tests indicated an important biologic inflammatory syndrome and a CD4 count = 214 cells/cmm (after only two
weeks of ART). The patient needed emergency surgery that showed
several necroses in the cecum and ascending colon wall, with secondary peritonitis. The cecum and the first part of the ascending
colon were ablated and the histopathological examination of the
operatory piece indicated granulomas suggestive for mycobacterial
infection. In situ PCR for Mycobacterium tuberculosis and MAC was effectuated and it was positive for Mycobacterium avium. The final
diagnosis was probably IRIS with digestive necrosis in an HIVinfected patient with the reactivation of a MAC latent infection. The
patient received clarithromycin, ethambutol and ciprofloxacin for
6 months and continued the same ART regimen, with favorable outcome. The prophylaxis for PCP and MAC weren’t necessary anymore
because the CD4 count was over 200 cells/cmm at discharge.
Conclusions
Every patient diagnosed with HIV should be rigorously monitored at
the start of ARV, not only for the potential side effects, but for the
risk of IRIS apparition. MAC etiology should be evocated in an HIVinfected patient who develops acute abdominal pain concomitant
with a rapid immune reconstruction.
Consent
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of
the written consent is available for review by the Editor of this
journal.
P25
The virologic outcome of the treatment of chronic hepatitis B
among HIV co-infected patients on HAART
Ivana Pesic Pavlovia1, Dubravka Salemovic2, Jovan Ranin2, Djordje
Jevtovic2
1
Department of Microbiology, Clinical Centre of Serbia, Belgrade, Serbia;
2
Belgrade University School of Medicine Infectious & Tropical Diseases
Hospital, Belgrade, Serbia
Correspondence: Ivana Pesic Pavlovia (ivanapesic69@yahoo.com) –
Department of Microbiology, Clinical Centre of Serbia, Belgrade, Serbia
BMC Infectious Diseases 2016, 16(Suppl 3):P25
Background
Since chronic hepatitis B (CHB) is associated with considerable morbidity and mortality, in HIV co-infected patients, it should be properly
treated. The main goal of antiviral therapy of CHB has been to maintain durable suppression of viral replication, precisely by achieving
and maintaining undetectable viremia by a sensitive PCR assay. All
HBV/HIV co-infected patients initiated lamivudine containing HAART,
which was switched to a tenofovir (TDF) based one when it became
available, and after HBV developed resistance to lamivudine.
Patients and methods
The study included all HBV/HIV co-infected patients who underwent
lamivudine containing HAART between 2000 and 2015, and were
switched to TDF based HAART, if experienced lamivudine failure. The
HBV infection status was assessed using commercial immunoassays
for different serological markers, such as HBsAg/Ab, HBeAg/Ab and
HBcAb, according to the manufacturer’s protocol. To detect and
quantify HBV DNA, real time PCR (Cobas TaqMan HBV Test version
2.0, Roche Molecular Systems, Branchburg, NJ, USA) was used. All
HBV DNA values are reported in IU/mL. For the presentation of HBVDNA levels logarithmic scale was used.
Results
After the mean duration of lamivudine containing HAART of 7.3 ±
3.2 years (range 1-15 years), lamivudine failure was recorded in 35/67
patients (52.2 %). Out of twenty-two remaining subjects with favorable virologic response to lamivudine, all achieved HBsAg loss, out of
which 2 patients developed anti-HBs antibodies, after 4.1 ± 3.1 years
(1-15 years), and 9 ± 2.8 years (7-15 years), respectively. After additional
2.1 ± 1.1 years of TDF containing HAART, hepatitis B viral load was
1.3 ± 1.1 log10 IU/mL HBV DNA. After TDF introduction, the probability
BMC Infectious Diseases 2016, Volume 16 Suppl 3
of achieving optimal treatment response, which included either suppression of HBV DNA to less than 20 IU/mL, and/or HBsAg loss, was
20 %, 60 % and 90 % after additional 2, 3 and 5 years of TDF containing
HAART, respectively. Taken together, among lamivudine, and/or TDF
containing HAART treated patients with HBV/HIV co-infection the estimated median time to achieving optimal anti-HBV treatment response
was 7 years. Since no HBV viral breakthrough occurred while on TDF,
we consider that a prolonged treatment with TDF containing HAART is
mandatory among those with suboptimal virologic suppression.
Conclusion
The benefit of tenofovir containing HAART among HBV/HIV co-infected
patients, who previously failed HBV therapy with lamivudine containing
HAART, was rather modest after approximately two years of treatment,
while the estimated treatment success reached 90 % after 5 years suggesting that the prolonged TDF therapy is mandatory to achieve the favorable response.
P26
A case of HIV encephalopathy with aphasia, agnosia, apraxia and
right homonymous hemianopsia
Ovidiu Roșca1, Andreea Ardeleanu2, Iulia Caramangiu2, Daniela Desaga1,
Valerica Bică2, Sorina Mitrescu2, Iosif Marincu1
1
Department of Infectious Diseases I, “Victor Babeș” University of
Medicine and Pharmacy Timișoara, Timișoara, Romania; 2Department of
Infectious Diseases, Clinical Hospital of Infectious Diseases and
Pneumology “Victor Babeș”, Timișoara, Romania
Correspondence: Ovidiu Roșca (roscaovidiu2003@yahoo.com) –
Department of Infectious Diseases I, “Victor Babeș” University of
Medicine and Pharmacy Timișoara, Timișoara, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P26
Background
The central nervous system (CNS) plays an important role in human
immunodeficiency virus (HIV) infection, being a major target of this
virus. In the CNS, which acts as a unique compartment and as a sanctuary, HIV can replicate independently from the plasma being protected from the host immune system and antiretroviral therapy. The
authors present a case of HIV encephalopathy with aphasia, agnosia,
apraxia and right homonymous hemianopsia.
Case report
We report the case of a 30 year-old male patient admitted in our department in January 2011, for receptive and expressive language disorders progressively installed (mixed aphasia); subsequently occur:
apraxia, agnosia for colors, right homonymous hemianopsia. The
patient's symptoms started two months before admission; he was
admitted to the neurology department where he tested HIV-positive.
Based on clinical elements, biological samples (number of leukocytes,
erythrocyte sedimentation ratio (ESR), C reactive protein (CRP), serum
glucose, blood culture, CD4, viral load (VL), HIV-RNA from cerebrospinal fluid (CSF), etc.), and imagistic evaluation (cerebral magnetic
resonance imaging - MRI) the diagnosis of HIV infection stage C3 and
HIV encephalitis was established. Antiretroviral treatment was started
with lopinavir/ritonavir 200/50 mg 4 tb/day and lamivudine/zidovudine 150/300 mg 2 tb/day. The clinical and biological evolution was
initially favorable. The patient was admitted again in November 2011
presenting in addition to the first admission right hemiplegia, seizures, urinary incontinence.
Cerebral MRI revealed extensive encephalitis lesions. In January 2011:
CD4: 164 cells/μL, HIV-RNA from blood: 210319 copies/mL, HIV-RNA
from CSF: 59240 copies/mL. Neurological exam: conscious, alert
(within aphasia), disoriented, possible walk, positive Romberg with
slight oscillations, Babinski sign positive in the right, expressive and
receptive language disorders, mixed aphasia, apraxia, agnosia for
colors, right homonymous hemianopsia. In November 2011, after
10 months of antiretroviral therapy: CD4: 495 cells/μL, HIV-RNA from
blood: undetectable, HIV-RNA from CSF: 9444 copies/mL. Despite administration of ARV with good CNS penetration, the evolution was
unfavorable and the patient died.
Page 26 of 29
Conclusion
Highly active antiretroviral therapy (HAART) is not enough to control
HIV associated dementia (HAD), the proof being the lack of reversibility of dementia in the presence of HAART in some cases, like the appearance of neurocognitive disorders in patients with good cellular
immunity. In our case, there was probably a compartmentalization of
HIV-1 in CSF, leading to the emergence of a resistant virus.
Consent
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the
written consent is available for review by the Editor of this journal.
P27
Molecular footprints on human immunodeficiency virus -1 genome
and association with phylogenetic clustering among subtype B
infected patients in Serbia
Marina Siljic1, Dubravka Salemovic2, Valentina Nikolic1, Djordje Jevtovic2,
Ivana Pesic-Pavlovic3, Jovan Ranin2, Marija Todorovic 1, Maja Stanojevic1
1
Institute of Microbiology and Immunology, University of Belgrade
Faculty of Medicine, Belgrade, Serbia; 2University Hospital for Infectious
and Tropical Diseases CCS, HIV/AIDS Unit, Belgrade, Serbia;
3
Microbiology Department, Clinical Center Serbia, Belgrade, Serbia
Correspondence: Marina Siljic (marinasiljic@gmail.com) – Institute of
Microbiology and Immunology, University of Belgrade Faculty of
Medicine, Belgrade, Serbia
BMC Infectious Diseases 2016, 16(Suppl 3):P27
The HIV evolutionary process is driven by complex interplay between
viral and host factors. Within hosts, the viral evolution is strongly influenced by natural selection as a result of a continuous effort to
evade the immune response. HIV successively fixes mutations that
allow it to evade immune response, acquiring combinations of polymorphisms in viral genome termed molecular footprint. The most
clearly defined footprints are those associated with HLA alleles that
are linked to successful control of HIV infection. Additionally, other
viral features may have important influences on viral evolution,
pathogenesis and disease outcomes, often through indirectly disturbing replicative capacity of virus, including resistance mutations to
antiretroviral drugs and other mutations in different HIV-1 genes. The
impact of positive selective pressure on viral diversity inter-host, as
opposed to spatial and temporal factors, is not equally clear.
We investigate the prevalence of different molecular footprints in
HIV pol region among subtype B infected patients in Serbia and their
persistence in HIV-1 transmission clusters. The presence of molecular
footprints associated with HLA alleles considered to be protective
(HLA B*57, HLA B*58, HLA B*13), as well as risk allele HLA B*35, transmission associated drug resistance mutations (TDR) and other mutations in viral pol sequences within the clades, will be explored.
Subtype B viral sequences obtained from patients at the Center for
HIV/AIDS, Institute for Infectious and Tropical Diseases in Belgrade, in
the period 2002-2015 will be included. Additionally we will include a
number of viral sequences downloaded from Los Alamos database.
Maximum likelihood phylogenetic trees will be constructed using
Mega and Paup software under the nucleotide substitution model
that will be chosen using JModelTest. Bootstrapped replicates of phylogenies will be sampled to assess support for clades. Bayesian
methods will be performed for reconstruction of phylogenetic trees.
Transmission clusters will be defined as those clades consisted of
three or more sequences with bootstrap value higher than 90 %,
Bayesian posterior probability higher than 0.9 and genetic distance
among sequences in the clade less than 1.5 %. In order to maintain
specificity in identifying true transmission clusters, we will perform
Phylopart software. Mutations specifically associated with transmitted
HIV-1 drug resistance will be analyzed with the Calibrated Population
Resistance Tool (CPR) and Stanford Genotypic Resistance Interpretation Algorithm.
Revealing how viral evolution within hosts is translated into viral
evolution inter hosts in one population is an important aspect in
BMC Infectious Diseases 2016, Volume 16 Suppl 3
determining how immune escape polymorphism and drug resistance might spread.
Acknowledgement
This work was partially funded by the Ministry of Education and Science
Republic of Serbia (grant No 175024).
P28
Neurosyphilis and human immunodeficiency virus infection:
double challenge
Nina-Ioana Șincu, Anca Georgescu, Brândușa Țilea, Iringo Zaharia Kezdi,
Andrea Incze, Cristina Gârbovan, Carmen Lucia Chiriac
Department of Infectious Diseases, University of Medicine and Pharmacy
Tîrgu-Mureș, Tîrgu-Mureș, Romania
Correspondence: Nina-Ioana Șincu (ninasincu@yahoo.com) –
Department of Infectious Diseases, University of Medicine and Pharmacy
Tîrgu-Mureș, Tîrgu-Mureș, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P28
Background
Treponema pallidum and human immunodeficiency virus share similar routes of transmission, as well as a predisposition for central nervous system impairment, with intertwining clinical symptoms. Coinfection represents a challenge, from the point of view of diagnosis,
possible complications and complex therapy.
Case report
We present the case of a young, 46-year-old male patient, with risk
factors for sexually transmitted diseases. The disease had an abrupt
onset, with repeated episodes of transient right limbs deficit, interpreted by the neurologist as repeated transient ischemic attacks,
with complete remission of symptoms between attacks.
Cerebral CT scan was negative, but cerebral angiography raised the
suspicion of left anterior cerebral artery dissection. Since the patient
had no obvious risk factors for cerebro-vascular disease, the neurologist considered a possible underlying infectious etiology. TPHA and
VDRL were positive, and the neurosyphilis diagnosis lead to investigations regarding other sexually transmitted diseases. Anti-HIV antibodies were positive, which is when the patient was referred to the
Clinic of Infectious Diseases. CD4+ T-lymphocytes count was 398
cells/μL. Positive TPHA and VDRL both from the patient’s serum and
from his cerebro-spinal fluid confirmed the diagnosis of neurosyphilis. The patient received antibiotic treatment with iv penicillin G for
neurosyphilis and started antiretroviral therapy: tenofovir + emtricitabine + darunavir + ritonavir. He tolerated therapy well. A cerebral
angio-MRI scan was performed in order to clarify the suspicion of left
anterior cerebral artery dissection, but the examination did not reveal
any arterial impairment.
Conclusions
Both syphilis and HIV infection raise significant diagnostic issues regarding central nervous system impairment. Complex diagnosis and
therapy of this co-infection requires the involvement of a multidisciplinary team. Central nervous system involvement can represent an inaugural manifestation in the course of HIV infection.
Consent
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the
written consent is available for review by the Editor of this journal.
P29
Differences between HIV-infected adults since childhood and non
HIV-infected persons on managing everyday life
Anca Elena Luca1, Florin Lazăr2, Adrian Luca3, Luminița Ene1, Roxana
Rădoi1, Adina Talnariu1, Silvia Suciu1, Cristian Achim4
1
“Dr. Victor Babeș” Hospital for Infectious and Tropical Diseases,
Bucharest, Romania; 2Faculty of Sociology and Social Work, University of
Bucharest, Bucharest, Romania; 3Faculty of Psychology and Education
Sciences, University of Bucharest, Bucharest, Romania; 4HIV
Neurobehavioral Research Center, University of California, San Diego,
USA
Page 27 of 29
Correspondence: Anca Elena Luca (ancaluca@gmail.com) – “Dr. Victor
Babeș” Hospital for Infectious and Tropical Diseases, Bucharest, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P29
Background
Children parenterally infected with HIV in the ‘90s are living for more
than 25 years. The study aimed to investigate the long-term neurocognitive consequences of living with HIV compared to an agematched control group.
Methods
HIV positive (HIV+) and negative (HIV-) young adults have undergone
extensive neurocognitive testing (2012-2015) using a standardized
battery assessing cognitive performance in 7 domains. Cognitive deficit was estimated by a composite global deficit score (GDS) > 0.5. Patients’ functioning was assessed using two self-report questionnaires:
Activities of Daily Living (ADL, α = 0.69) which reports the competence in performing basic tasks of everyday life required for independent living such as housekeeping, shopping, cooking, managing
finances etc. and Patient’s Assessment of Own Functioning Inventory
(PAOFI α = 0.93): rated patients’ self-perceptions regarding the adequacy of their functioning in various everyday tasks and activities
for items in five subscales (memory, language and communication,
use of hands, sensory-perceptual, cognitive and intellectual functions) with answers ranging on a 6-point scale. Depressive symptoms
were assessed with Beck Depression Inventory II (BDI α = 0.89). Analysis of variance (ANOVA) compared HIV+ with HIV- patients in terms
of cognitive performance (GDS), depression (BDI), self-perceived functioning (PAOFI), cognitive complaints, level of education, parent’s
education, use of academic abilities, different confounders (medical,
psychiatric etc.) employment status and incomes.
Results
The study group included 233 HIV+ and 53 HIV- participants with
median age of 24.3 years for both groups. HIV+ participants were
less educated (F = 9.419, sig. = 0.002), less likely to be employed (F =
15.25, sig. = 0.000), more depressed (F = 4.572, sig. = 0.033), and had
a higher GDS (F = 14.617, sig. = 0.000) than their HIV- counterparts.
Based on ANOVA the effect size of employment status on depression
(F = 5.970, sig. = 0.003) is significant and higher than the effect of HIV
status (F = 4.712, sig. = 0.031). However, there were not statistically
significant differences in terms of PAOFI, ADL, social interactions,
various confounding factors (e.g. medical, psychiatric, language, educational), parents’ education or monthly incomes.
Conclusion
Overall young adults with chronic HIV infection had higher rates of
neurocognitive impairment, more depressive symptoms, and were less
likely to have a job than HIV uninfected matched controls. Having similar levels of self-perceived functioning and cognitive complaints suggests a coping mechanism developed by HIV+ participants to face the
everyday challenges of living with the infection.
Acknowledgement
NIH-funded grant R01MH094159-01 “Long term effects of chronic HIV
infection on the developing brain”.
P30
Molecular detection of Bartonella quintana in a HIV
immunodepressed patient with fever and isolated
lymphadenopathy - Case report
Diana Gabriela Iacob1, Dragoș Florea1,2, Simona Iacob1,2
1
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest,
Romania; 2Carol Davila University of Medicine and Pharmacy, Bucharest,
Romania
Correspondence: Diana Gabriela Iacob (dianagiacob@gmail.com) –
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest,
Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P30
Background
Bartonella quintana is an opportunistic pathogen with a wide array of
presentations, including isolated lymphadenopathies. We report a
BMC Infectious Diseases 2016, Volume 16 Suppl 3
Page 28 of 29
case of Bartonella quintana detected using a PCR assay in a HIVpositive patient with axillary lymphadenopathy in which the gold
standard culture tests were unavailable.
Case report
We describe the case of a 31 year-old patient with HIV-HCV coinfection, previously diagnosed and treated for tuberculous lymphadenopathy who presented for fever, headaches, weight loss and painful
axillary lymphadenopathy for the past 6 weeks. The patient was nonadherent to the antiretroviral treatment and reported close contact
with cats. Clinical examination revealed an isolated, well defined left
axillary lymphadenopathy of 5/6 cm, tender and mobile, with no
overlying inflammatory signs. Laboratory assays revealed a severe immunosuppression (CD4 = 11 cells/cmm) and a moderate inflammatory syndrome, with negative procalcitonin. Blood culture and PCR
for Mycobacterium tuberculosis (Cepheid GeneXpert MTB/RIF) were
negative, as were the serologic analysis for Toxoplasma and syphilis.
Nevertheless a blood sample sent for PCR coupled with mass spectrometry retrieved Bartonella quintana. Other imaging studies did not
reveal any other mediastinal, retroperitoneal or mesenteric lymphadenopathies, cerebral MRI showed cortical atrophy and cerebrospinal fluid studies were normal. Unfortunately, the patient refused
lymph node biopsy and we could not rule out a co-infection with
Mycobacterium tuberculosis in the setting of an incomplete antituberculosis therapy. He underwent a successful 2 week-course of ciprofloxacin
(the patient was allergic to clarithromycin and cotrimoxazole) along
with the anti-tuberculous treatment with izoniazid/rifampicin/streptomycin and antiretroviral treatment.
Conclusions
The case raises the awareness for the importance of molecular diagnostic assays and also highlights the possibility for Bartonella infections in previous tuberculous lymphadenopathies.
Consent
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of
the written consent is available for review by the Editor of this
journal.
56.3 % lived in urban area, 13.5 % had low education, 51.4 % were
married/couples, 62.2 % travelled or worked abroad more than
6 months, especially in Italy (38.8 %). Positive HIV tests in other countries were found in 31 % adults. Symptomatic diseases were indicative for HIV testing in 21.3 %. The main reasons for volunteer HIV
testing were the screening programs for sexually transmitted diseases (23.3 %), tuberculosis (10.68 %), blood donors (15.5 %), pregnancy (45.6 % of fertile women) and circumstances of a HIV positive
partner (36.8 %). Frequency of the viral hepatitis was 21.3 % for HBV
and 8.5 % for HCV. Baseline LCD4 was 379 ± 336.7/μL, corresponding
to 56.3 % late presenters and 23.3 % very late presenters. Antiretroviral treatment was initiated in 63.2 % patients, mostly with protease
inhibitors. The retention in care was 91.3 %, while 9 patients were
lost from evidence. Mortality was 14.6 %. The risk of death was correlated with older age, single status, work abroad, lower immunity and
tuberculosis as “sentinel” disease.
Conclusions
Mortality in patients newly diagnosed with HIV infection tends to increase, although late presentation and the retention in care were improved in the last years. Travel and work migration are run on risks
for HIV transmission and poor prognostic. The current strategy for
better control of HIV infection, is earlier time diagnostic, continuing
the screening programs and encouraging the volunteer testing.
P31
Present epidemiological characteristics of HIV/AIDS newly
diagnosed cases in South-Eastern Romania
Manuela Arbune1,2, Miruna Drăgănescu1,2, Alina Iancu2,3
1
Clinical Department, “Dunărea de Jos” University Galați, Galați, Romania;
2
Infectious Diseases Clinical Hospital Galați, Galați, Romania;
3
Morphologic and Functional Sciences Department, “Dunărea de Jos”
University Galați, Galați, Romania
Correspondence: Manuela Arbune (manuela.arbune@ugal.ro) – Clinical
Department, “Dunărea de Jos” University Galați, Galați, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P31
Background
We are living in symbiosis with a large variety of viruses, bacteria,
fungi and parasites. Some of them act like opportunists when the immune defense gets weak. Part of our immunological reactivity is
gender-related and we can speculate that there could be a genderlinked permissiveness for specific microbes or, vice-versa, specific
germs have predilection for males or for females. Our objective was
to explore a group of patients with very low immunological status, in
order to find if there is a gender affinity of the opportunistic agents
implied in their infections.
Method
Our retrospective study analyzed all HIV-positive adult patients
(>18 years-old) admitted in one year interval (01 January-31 December 2015) in the National Institute for Infectious Diseases with a
newly diagnosed invasive opportunistic infection (OI): mycobacteriosis - tuberculosis (TB) and atypical mycobacteriosis, P. jirovecii pneumonia (PJP), cryptococcosis, toxoplasmosis, cytomegalovirus (CMV)
infections, Kaposi sarcoma (KS), progressive multifocal leukoencephalitis (PML). Three parameters were further analyzed: sex, age and the
patient’s outcome.
Results
There were 118 HIV-positive patients admitted with at least one OI,
76 male patients (64 %) and 42 female patients (36 %), with a sex
distribution of 1.8:1. The median age of the entire group was 33 [2640] years old. There is significant difference between median age in
men (34) and in women (32), p = .028. The outcome was fatal in 13
patients (11.01 %), with a mortality rate being double in male
(13.1 %) versus female (7.1 %), p = 0.3. There was TB predominance
among IO, consisting in 63 cases (53.38 %), 2:1 male:female ratio,
with a fatal course in 4 cases: 3:1 male:female. PJP was diagnosed as
IO in 20 cases, 3:2 male:female, with one death. For toxoplasmosis
(10 cases), the sex-ratio was 2:3 male:female, with one death. PML
Background
Patients from the Romanian HIV/AIDS pediatric cohort have grown
up to the current age 25-29 years old. They signify 53.3 % from 328
beneficiaries of HIV Clinic Galați. New HIV/AIDS cases with various
transmission ways are continuing to be diagnosed year by year. A
previous evaluation (2005 - 2010) in Galați reported 73 % HIV late
presenters (LCD4 < 350/μL). The social, economic, and political
changes that occurred in Europe have impact on HIV epidemic.
Methods
We have retrospectively evaluated the new HIV diagnosed cases in
Galați Clinic, from 2011 to 2015. The analysis of the HIV case report
form included demographic data, risk factors of virus transmission,
baseline immunity, co-morbidities and the antiretroviral treatment.
The data were compared with situation 2005-2010. Statistical analysis
performed descriptive and correlation tests, with significance level
<0.005.
Results
An average of 20.2 new HIV cases were diagnosed yearly. Three children under age 13 were perinatally HIV infected. The average age in
adults was 33.1 ± 12.3 years. Among 106 patients, 61.7 % were males,
P32
The gender’s preferences among opportunists?
Ruxandra Moroti1,2, Cristian M Niculae1, Simona Merisor1, Eliza Manea1,
Serban Benea1,2, Andrada Stan1, Raluca Hrisca1, Raluca Jipa1,2,
Diana Tanase1, Adriana Hristea1,2
1
Clinical Department, National Institute for Infectious Diseases “Prof. Dr.
Matei Balș”, Bucharest, Romania; 2Carol Davila University of Medicine and
Pharmacy, Bucharest, Romania
Correspondence: Ruxandra Moroti (ruxandra_moroti@yahoo.com) –
Clinical Department, National Institute for Infectious Diseases “Prof. Dr.
Matei Balș”, Bucharest, Romania
BMC Infectious Diseases 2016, 16(Suppl 3):P32
BMC Infectious Diseases 2016, Volume 16 Suppl 3
was an IO in 10 cases, 4:6 male:female, with a fatal outcome in 3
male patients. Kaposi was diagnosed in 10 cases, 4:1 male:female
and 2 cases were fatal (2 males). PML was IO in 10 cases, 1:1, with 3
fatal cases in males. In 7 cases, CMV was implied (4:3 male:female).
Cryptococcosis was involved in 5 cases, all males, with 4 deaths.
Conclusions
OI roughly predominated in males in our study. Within specific OI
categories, the sex-ratio seems to be different, the male predominance being perceptible for Cryptococcus, MTB and Kaposi and a female predominance for Toxoplasma and polyomaviruses.
P33
Polymorphism of interleukin-28B gene in persons with chronic
hepatitis C from Croatia
Ivana Grgic1, Ana Planinic1, Lana Gorenec1, Snjezana Zidovec Lepej1,
Adriana Vince2
1
Department for Molecular Diagnostic and Flow Cytometry, University
Hospital for Infectious Diseases Zagreb, Zagreb, Croatia; 2Department of
Viral Hepatitis, University Hospital for Infectious Diseases Zagreb, Zagreb,
Croatia
Correspondence: Ivana Grgic (ivanahobby@gmail.com) – Department
for Molecular Diagnostic and Flow Cytometry, University Hospital for
Infectious Diseases Zagreb, Zagreb, Croatia
BMC Infectious Diseases 2016, 16(Suppl 3):P33
Page 29 of 29
Background Polymorphism of the promoter region in the gene coding for interleukin-28B (IL-28B) is associated with the natural history
of HCV infection and response to antiviral and immunomodulatory
therapy. Despite the fact that the predictive role of IL-28B genotyping is decreasing in the era of highly successfully direct acting antiviral (DAA)-based treatment, it remains to be useful in resourcelimited settings with limited access to new treatment options.
Methods
The study included 380 Caucasian patients with chronic hepatitis C
receiving clinical care at the Department of Viral Hepatitis of the University Hospital for Infectious Diseases, Zagreb and Croatian Reference Center for Viral Hepatitis. Human DNA was extracted from
whole blood by using Qiagen Blood Mini kit. Detection of single nucleotide polymorphism (SNP) rs12979860 was determined by using a
real-time PCR test IL28B LightMix® Kit IL28B rs12979860 (TIB Molbiol,
Berlin, Germany) and LightCycler® FastStart DNA Master HybProbe
(Roche Diagnostic, Germany).
Results
Analysis of rs12979860 SNP in the IL-28B gene revealed 222 of 380
(58.4 %) CT heterozygotes, followed by C homozygotes (102 of 380
patients, 26.8 %) and T homozygous patients were the least frequent
(56 of 380 patients, 14.7 %).
Conclusion
The patterns of IL-28 polymorphism in Croatian patients with chronic
hepatitis C is in accordance with other results for Caucasians.
Submit your next manuscript to BioMed Central
and we will help you at every step:
• We accept pre-submission inquiries
• Our selector tool helps you to find the most relevant journal
• We provide round the clock customer support
• Convenient online submission
• Thorough peer review
• Inclusion in PubMed and all major indexing services
• Maximum visibility for your research
Submit your manuscript at
www.biomedcentral.com/submit