Additional file 1: Table S1. Sociodemographic, clinical, and laboratory data of HIV-1-positive in... more Additional file 1: Table S1. Sociodemographic, clinical, and laboratory data of HIV-1-positive individuals included in the study categorized according to the presence (G1) or absence (G2) of TB. Table S2. Distribution of HLA-B, HLA-C, and KIR genetic profiles found in this study. Table S3. Distribution of HLA-B and HLA-C serological epitopes of subjects included in this study stratified by groups. Table S4. Distribution of HLA-B alleles of the subjects included in this study and the Brazilian general population (data from the Brazilian Registry of Bone Marrow Donors - REDOME). Table S5. Frequency of KIR genotypes and mapping of the inhibitory/activator genes among the subjects included in this study. Table S6. Distribution of KIR genotypes of subjects included in this study stratified by groups. Table S7. Sociodemographic, clinical, and laboratory data of HIV-TB individuals with and without IRIS.
Background Tuberculosis (TB) and AIDS are the leading causes of infectious disease death worldwid... more Background Tuberculosis (TB) and AIDS are the leading causes of infectious disease death worldwide. In some TB-HIV co-infected individuals treated for both diseases simultaneously, a pathological inflammatory reaction termed immune reconstitution inflammatory syndrome (IRIS) may occur. The risk factors for IRIS are not fully defined. We investigated the association of HLA-B, HLA-C, and KIR genotypes with TB, HIV-1 infection, and IRIS onset. Methods Patients were divided into four groups: Group 1- TB+/HIV+ (n = 88; 11 of them with IRIS), Group 2- HIV+ (n = 24), Group 3- TB+ (n = 24) and Group 4- healthy volunteers (n = 26). Patients were followed up at INI/FIOCRUZ and HGNI (Rio de Janeiro/Brazil) from 2006 to 2016. The HLA-B and HLA-C loci were typed using SBT, NGS, and KIR genes by PCR-SSP. Unconditional logistic regression models were performed for Protection/risk estimation. Results Among the individuals with TB as the outcome, KIR2DS2 was associated with increased risk for TB ons...
We evaluated acceptability of cervico-vaginal self-collection (CVSC) and prevalence of human papi... more We evaluated acceptability of cervico-vaginal self-collection (CVSC) and prevalence of human papillomavirus (HPV) in Human immunodeficiency virus (HIV)-infected and HIV-uninfected women living in the Tapajós region, Amazon, Brazil. Cross-sectional study recruited 153 non-indigenous women (HIV-uninfected, n = 112 and HIV-infected, n = 41) who voluntarily sought assistance in health services. Peripheral blood for HIV screening and cervical scraping (CS) for HPV detection were collected. Women who accepted to perform CVSC received instructions and individual collection kits. Risk factors for high-risk HPV genotypes (hrHPV) were identified by uni- and multivariate analyses. The overall acceptability of CVSC was 87%. Only HIV-infected women had cytological abnormalities (12.2%). Prevalence of any HPV and hrHPV infection was 42.9% and 47.9% for HIV-uninfected and 97.6% and 77.5% for HIV-infected women, respectively. There was significant agreement in the detection of HPV (88%, 0.76, 95% c...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2018
Rates of adverse pregnancy outcomes for women who conceive on ART may be increased, but data are ... more Rates of adverse pregnancy outcomes for women who conceive on ART may be increased, but data are conflicting. Asymptomatic HIV-infected, non-breastfeeding women with pre-ART CD4 counts ≥400 cells/mm3 who started ART during pregnancy were randomized after delivery to continue (cART) or discontinue ART (dART). Fifty-six sites in Argentina, Botswana, Brazil, China, Haiti, Peru, Thailand and the US participated. Women randomized to dART were recommended to restart if a subsequent pregnancy occurred or for clinical indications. Using both intent-to-treat (ITT) and as-treated approaches, we performed Fisher's exact test to compare subsequent pregnancy outcomes among women randomized to cART versus dART. Subsequent pregnancies occurred in 277/1652 (17%) women (cART: 144/827, dART: 133/825). A pregnancy outcome was recorded for 266 (96%) women with median age 27 years (IQR 24, 31) and median CD4+ T-cell count 638 cells/mm3 (IQR 492, 833). When spontaneous abortions and stillbirths were ...
The Pediatric infectious disease journal, Jan 10, 2018
HIV exposed uninfected (HEU) infants are a growing population with potentially poor health outcom... more HIV exposed uninfected (HEU) infants are a growing population with potentially poor health outcomes. We evaluated morbidity and mortality in HEU formula-fed infants enrolled in the NICHD HPTN 040/PACTG 1043 trial. Infectious morbidity, mortality, and undernutrition were evaluated within a cohort of 1,000 HEU infants enrolled between 4/2004 and 4/2010 in Brazil (N=766) and South Africa (N=234) as part of the NICHD/HPTN 040 trial of three different antiretroviral regimens to decrease intrapartum HIV vertical transmission. Twenty three percent of infants had at least 1 infectious serious adverse effect (ISAE). Infants born to mothers with <12 years of education (AOR 2.6, 95% CI 1.2-5.9), with maternal viral load of >1,000,000 copies/mL at delivery (AOR 9.9, 95% CI 1.6-63.1) were more likely to have ISAEs. At 6 months, the infant mortality rate per 1,000 live births overall was 22 ± 2.6, 9.1 ± 1.8 in Brazil, and 64.1 ± 3 in South Africa. Undernutrition and stunting peaked at 1 mon...
The Pediatric infectious disease journal, Jan 9, 2018
Congenital cytomegalovirus (CMV) infection (cCMV) is an important cause of hearing loss and cogni... more Congenital cytomegalovirus (CMV) infection (cCMV) is an important cause of hearing loss and cognitive impairment. Prior studies suggest that HIV-exposed children are at higher risk of acquiring cCMV. We assessed the presence, magnitude, and risk factors associated with cCMV among infants born to HIV-infected women, who were not receiving antiretrovirals during pregnancy. cCMV and urinary CMV load were determined in a cohort of infants born to HIV-infected women not receiving antiretrovirals during pregnancy. Neonatal urines obtained at birth were tested for CMV DNA by qualitative and reflex quantitative real-time PCR. Urine specimens were available for 992 (58.9%) of 1684 infants; 64 (6.5%) were CMV-positive. Mean CMV load (VL) was 470,276 copies/ml (range: <200-2,000,000 copies/ml). Among 89 HIV-infected infants, 16 (18%) had cCMV versus 42 (4.9%) of 858 HIV-exposed, uninfected infants (p <0.0001). cCMV was present in 23.2% of infants with in utero and 9.1% infants with intra...
Revista do Instituto de Medicina Tropical de Sao Paulo, Jan 8, 2018
The increase in HIV transmissibility in non-ulcerative sexually transmitted infection is already ... more The increase in HIV transmissibility in non-ulcerative sexually transmitted infection is already well-established. It is estimated that symptomatic carriers of N. gonorrhoeae and C. trachomatis have a relative risk of 4.8-fold and 3.6-fold, respectively, for the sexual acquisition of HIV. This type of evaluation for asymptomatic urethritis is necessary to reinforce strategies to combat HIV transmission. This study aims to assess the prevalence of patients with asymptomatic urethritis among men diagnosed with HIV-1 and determine the risk factors associated with this infection. We enrolled a total of 115 male patients aged 18 years or older who have been diagnosed with HIV infection and have no symptoms of urethritis or other sexually transmitted infections and who have been evaluated between May and August 2015 in a follow-up visit at the Immunology Outpatient Clinic of a Brazilian University Hospital. Four asymptomatic patients were positive for C. trachomatis and were considered as...
Sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), Neisseria gonorrhoea... more Sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and cytomegalovirus (CMV) may lead to adverse pregnancy and infant outcomes. The role of combined maternal STIs in HIV mother-to-child transmission (MTCT) was evaluated in mother-infant pairs from NICHD HPTN 040. Urine samples from HIV-infected pregnant women during labor were tested by polymerase chain reaction (PCR) for CT, NG, and CMV. Infant HIV infection was determined by serial HIV DNA PCR testing. Maternal syphilis was tested by VDRL and confirmatory treponemal antibodies. A total of 899 mother-infant pairs were evaluated. Over 30% had at least one of the following infections (TP, CT, NG, and/or CMV) detected at the time of delivery. High rates of TP (8.7%), CT (17.8%), NG (4%), and CMV (6.3%) were observed. HIV MTCT was 9.1% (n = 82 infants). HIV MTCT was 12.5%, 10.3%, 11.1%, and 26.3% among infants born to women with CT, TP, NG or CMV respectivel...
Journal of acquired immune deficiency syndromes (1999), Jan 28, 2017
We evaluated HIV drug resistance in adults who received early versus delayed antiretroviral thera... more We evaluated HIV drug resistance in adults who received early versus delayed antiretroviral therapy (ART) in a multi-national trial (HPTN 052, enrollment 2005-2010). In HPTN 052, 1,763 index participants were randomized to start ART at a CD4 cell count of 350-550 cells/mm3 (early ART arm) or <250 cells/mm3 (delayed ART arm). In May 2011, interim study results showed benefit of early ART, and all participants were offered ART regardless of CD4 cell count; the study ended in 2015. Virologic failure was defined as two consecutive viral loads >1,000 copies/mL >24 weeks after ART initiation. Drug resistance testing was performed for pre-treatment (baseline) and failure samples from participants with virologic failure. HIV genotyping results were obtained for 211/249 participants (128 early ART arm; 83 delayed ART arm) with virologic failure. Drug resistance was detected in 4.7% of participants at baseline; 35.5% had new resistance at failure. In univariate analysis, the frequenc...
In occult hepatitis B infection (OBI), hepatitis B virus DNA (HBV DNA) can be detected in serum s... more In occult hepatitis B infection (OBI), hepatitis B virus DNA (HBV DNA) can be detected in serum samples; however, oral fluid collection for detection of HBV DNA has not yet been explored, despite the availability of collection devices. Serum and oral fluid samples from 45 hepatitis B core antibody (anti-HBc)-positive patients were collected for the amplification of the HBV polymerase gene. HBV DNA was detected in five serum and four oral fluid samples (the detection limit for oral fluid was 1.656 log IU/mL in paired serum). In conclusion, simple methodologies of sample collection and in-house polymerase chain reaction (PCR) allowed detection of HBV DNA, and these could be used to improve the diagnosis of OBI, especially in locations with limited resources.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 23, 2017
Congenital Zika virus (ZIKV) syndrome is a newly identified condition resulting from infection du... more Congenital Zika virus (ZIKV) syndrome is a newly identified condition resulting from infection during pregnancy. We analyzed outcome data from a mother-infant cohort in Rio de Janeiro in order to assess whether clinical severity of maternal ZIKV infection was associated with maternal virus load, prior dengue antibodies or abnormal pregnancy/infant outcomes. A clinical severity assessment tool was developed based on duration of fever, severity of rash, multisystem involvement and duration of symptoms during ZIKV infection. ZIKV-RNA load was quantified by PCR cycles in blood/ urine. Dengue IgG antibodies were measured at baseline. Adverse outcomes were defined as fetal loss or a live infant with grossly abnormal clinical or brain imaging findings. Regression models were used to study potential associations. 131 ZIKV-PCR positive pregnant women were scored for clinical disease severity, 6 (4.6%) had mild disease, 98 (74.8%) had moderate disease and 27 (20.6%) severe manifestations of Z...
Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral tr... more Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significan...
Health benefits of postpartum antiretroviral therapy (ART) for human immunodeficiency virus (HIV)... more Health benefits of postpartum antiretroviral therapy (ART) for human immunodeficiency virus (HIV) positive women with high CD4+ T-counts have not been assessed in randomized trials. Asymptomatic, HIV-positive, non-breastfeeding women with pre-ART CD4+ T-cell counts ≥ 400 cells/mm3 started on ART during pregnancy were randomized up to 42 days after delivery to continue or discontinue ART. Lopinavir/ritonavir plus tenofovir/emtricitabine was the preferred ART regimen. The sample size was selected to provide 88% power to detect a 50% reduction from an annualized primary event rate of 2.07%. A post-hoc analysis evaluated HIV/AIDS-related and World Health Organization (WHO) Stage 2 and 3 events. All analyses were intent to treat. 1652 women from 52 sites in Argentina, Botswana, Brazil, China, Haiti, Peru, Thailand and the US were enrolled (1/2010-11/2014). Median age was 28 years and major racial categories were Black African (28%), Asian (25%) White (15%). Median entry CD4 count was 696...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 22, 2017
Cytomegalovirus (CMV) urinary shedding in HIV-infected pregnant women was evaluated to determine ... more Cytomegalovirus (CMV) urinary shedding in HIV-infected pregnant women was evaluated to determine whether it poses an increased risk for congenital CMV infection (cCMV). A subset of mother-infant pairs enrolled in the perinatal NICHD HPTN 040 study (distinguished by no antiretroviral use before labor) was evaluated. Maternal and infant urines were tested by qualitative real-time polymerase chain reaction (RT-PCR) for CMV DNA with quantitative RT-PCR performed on positive specimens. Urine specimens were available for 260 women, 85.4% from the Americas and 14.6% from South Africa. Twenty-four women (9.2%) had detectable CMV viruria by qualitative PCR. Maternal CMV viruria was not associated with mean CD4 cell counts or HIV viral load but was associated with younger maternal age (p=0.02). Overall, ten of 260 infants (3.8%) had cCMV. Women with detectable peripartum CMV viruria were more likely to have infants with cCMV than those without: 20.8% (5/24) versus 2.1% (5/236), (p=0.0001). Wo...
Journal of acquired immune deficiency syndromes (1999), Jan 16, 2016
HIV Prevention Trials Network (HPTN) 052 demonstrated that antiretroviral therapy (ART) prevents ... more HIV Prevention Trials Network (HPTN) 052 demonstrated that antiretroviral therapy (ART) prevents HIV transmission in serodiscordant couples. HIV from index-partner pairs was analyzed to determine the genetic linkage status of partner infections. Forty-six infections were classified as linked, indicating that the index was the likely source of the partner's infection. Lack of viral suppression and higher index viral load were associated with linked infection. Eight linked infections were diagnosed after the index started ART: four near the time of ART initiation and four after ART failure. Linked infections were not observed when the index participant was stably suppressed on ART.
Antiretroviral (ARV) resistance mutations in human immunodeficiency virus type 1 (HIV-1) infectio... more Antiretroviral (ARV) resistance mutations in human immunodeficiency virus type 1 (HIV-1) infection may reduce the efficacy of prophylactic therapy to prevent mother-to-child transmission (PMTCT) and future treatment options. This study evaluated the diversity and the prevalence of transmitted drug resistance (TDR) in protease (PR) and reverse transcriptase (RT) regions of HIV-1 pol gene among 87 ARV-naive HIV-1-infected pregnant women from Rio de Janeiro, Brazil, between 2012 and 2015. The viral diversity comprised HIV-1 subtypes B (67.8%), F1 (17.2%), and C (4.6%); the circulating recombinant forms 12_BF (2.3%), 28/29_BF, 39_BF, 02_AG (1.1% each) and unique recombinants forms (4.5%). The overall prevalence of any TDR was 17.2%, of which 5.7% for nucleoside RT inhibitors, 5.7% for non-nucleoside RT inhibitors, and 8% for PR inhibitors. The TDR prevalence found in this population may affect the virological outcome of the standard PMTCT ARV-regimens, reinforcing the importance of continuous monitoring.
Additional file 1: Table S1. Sociodemographic, clinical, and laboratory data of HIV-1-positive in... more Additional file 1: Table S1. Sociodemographic, clinical, and laboratory data of HIV-1-positive individuals included in the study categorized according to the presence (G1) or absence (G2) of TB. Table S2. Distribution of HLA-B, HLA-C, and KIR genetic profiles found in this study. Table S3. Distribution of HLA-B and HLA-C serological epitopes of subjects included in this study stratified by groups. Table S4. Distribution of HLA-B alleles of the subjects included in this study and the Brazilian general population (data from the Brazilian Registry of Bone Marrow Donors - REDOME). Table S5. Frequency of KIR genotypes and mapping of the inhibitory/activator genes among the subjects included in this study. Table S6. Distribution of KIR genotypes of subjects included in this study stratified by groups. Table S7. Sociodemographic, clinical, and laboratory data of HIV-TB individuals with and without IRIS.
Background Tuberculosis (TB) and AIDS are the leading causes of infectious disease death worldwid... more Background Tuberculosis (TB) and AIDS are the leading causes of infectious disease death worldwide. In some TB-HIV co-infected individuals treated for both diseases simultaneously, a pathological inflammatory reaction termed immune reconstitution inflammatory syndrome (IRIS) may occur. The risk factors for IRIS are not fully defined. We investigated the association of HLA-B, HLA-C, and KIR genotypes with TB, HIV-1 infection, and IRIS onset. Methods Patients were divided into four groups: Group 1- TB+/HIV+ (n = 88; 11 of them with IRIS), Group 2- HIV+ (n = 24), Group 3- TB+ (n = 24) and Group 4- healthy volunteers (n = 26). Patients were followed up at INI/FIOCRUZ and HGNI (Rio de Janeiro/Brazil) from 2006 to 2016. The HLA-B and HLA-C loci were typed using SBT, NGS, and KIR genes by PCR-SSP. Unconditional logistic regression models were performed for Protection/risk estimation. Results Among the individuals with TB as the outcome, KIR2DS2 was associated with increased risk for TB ons...
We evaluated acceptability of cervico-vaginal self-collection (CVSC) and prevalence of human papi... more We evaluated acceptability of cervico-vaginal self-collection (CVSC) and prevalence of human papillomavirus (HPV) in Human immunodeficiency virus (HIV)-infected and HIV-uninfected women living in the Tapajós region, Amazon, Brazil. Cross-sectional study recruited 153 non-indigenous women (HIV-uninfected, n = 112 and HIV-infected, n = 41) who voluntarily sought assistance in health services. Peripheral blood for HIV screening and cervical scraping (CS) for HPV detection were collected. Women who accepted to perform CVSC received instructions and individual collection kits. Risk factors for high-risk HPV genotypes (hrHPV) were identified by uni- and multivariate analyses. The overall acceptability of CVSC was 87%. Only HIV-infected women had cytological abnormalities (12.2%). Prevalence of any HPV and hrHPV infection was 42.9% and 47.9% for HIV-uninfected and 97.6% and 77.5% for HIV-infected women, respectively. There was significant agreement in the detection of HPV (88%, 0.76, 95% c...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2018
Rates of adverse pregnancy outcomes for women who conceive on ART may be increased, but data are ... more Rates of adverse pregnancy outcomes for women who conceive on ART may be increased, but data are conflicting. Asymptomatic HIV-infected, non-breastfeeding women with pre-ART CD4 counts ≥400 cells/mm3 who started ART during pregnancy were randomized after delivery to continue (cART) or discontinue ART (dART). Fifty-six sites in Argentina, Botswana, Brazil, China, Haiti, Peru, Thailand and the US participated. Women randomized to dART were recommended to restart if a subsequent pregnancy occurred or for clinical indications. Using both intent-to-treat (ITT) and as-treated approaches, we performed Fisher's exact test to compare subsequent pregnancy outcomes among women randomized to cART versus dART. Subsequent pregnancies occurred in 277/1652 (17%) women (cART: 144/827, dART: 133/825). A pregnancy outcome was recorded for 266 (96%) women with median age 27 years (IQR 24, 31) and median CD4+ T-cell count 638 cells/mm3 (IQR 492, 833). When spontaneous abortions and stillbirths were ...
The Pediatric infectious disease journal, Jan 10, 2018
HIV exposed uninfected (HEU) infants are a growing population with potentially poor health outcom... more HIV exposed uninfected (HEU) infants are a growing population with potentially poor health outcomes. We evaluated morbidity and mortality in HEU formula-fed infants enrolled in the NICHD HPTN 040/PACTG 1043 trial. Infectious morbidity, mortality, and undernutrition were evaluated within a cohort of 1,000 HEU infants enrolled between 4/2004 and 4/2010 in Brazil (N=766) and South Africa (N=234) as part of the NICHD/HPTN 040 trial of three different antiretroviral regimens to decrease intrapartum HIV vertical transmission. Twenty three percent of infants had at least 1 infectious serious adverse effect (ISAE). Infants born to mothers with <12 years of education (AOR 2.6, 95% CI 1.2-5.9), with maternal viral load of >1,000,000 copies/mL at delivery (AOR 9.9, 95% CI 1.6-63.1) were more likely to have ISAEs. At 6 months, the infant mortality rate per 1,000 live births overall was 22 ± 2.6, 9.1 ± 1.8 in Brazil, and 64.1 ± 3 in South Africa. Undernutrition and stunting peaked at 1 mon...
The Pediatric infectious disease journal, Jan 9, 2018
Congenital cytomegalovirus (CMV) infection (cCMV) is an important cause of hearing loss and cogni... more Congenital cytomegalovirus (CMV) infection (cCMV) is an important cause of hearing loss and cognitive impairment. Prior studies suggest that HIV-exposed children are at higher risk of acquiring cCMV. We assessed the presence, magnitude, and risk factors associated with cCMV among infants born to HIV-infected women, who were not receiving antiretrovirals during pregnancy. cCMV and urinary CMV load were determined in a cohort of infants born to HIV-infected women not receiving antiretrovirals during pregnancy. Neonatal urines obtained at birth were tested for CMV DNA by qualitative and reflex quantitative real-time PCR. Urine specimens were available for 992 (58.9%) of 1684 infants; 64 (6.5%) were CMV-positive. Mean CMV load (VL) was 470,276 copies/ml (range: <200-2,000,000 copies/ml). Among 89 HIV-infected infants, 16 (18%) had cCMV versus 42 (4.9%) of 858 HIV-exposed, uninfected infants (p <0.0001). cCMV was present in 23.2% of infants with in utero and 9.1% infants with intra...
Revista do Instituto de Medicina Tropical de Sao Paulo, Jan 8, 2018
The increase in HIV transmissibility in non-ulcerative sexually transmitted infection is already ... more The increase in HIV transmissibility in non-ulcerative sexually transmitted infection is already well-established. It is estimated that symptomatic carriers of N. gonorrhoeae and C. trachomatis have a relative risk of 4.8-fold and 3.6-fold, respectively, for the sexual acquisition of HIV. This type of evaluation for asymptomatic urethritis is necessary to reinforce strategies to combat HIV transmission. This study aims to assess the prevalence of patients with asymptomatic urethritis among men diagnosed with HIV-1 and determine the risk factors associated with this infection. We enrolled a total of 115 male patients aged 18 years or older who have been diagnosed with HIV infection and have no symptoms of urethritis or other sexually transmitted infections and who have been evaluated between May and August 2015 in a follow-up visit at the Immunology Outpatient Clinic of a Brazilian University Hospital. Four asymptomatic patients were positive for C. trachomatis and were considered as...
Sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), Neisseria gonorrhoea... more Sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and cytomegalovirus (CMV) may lead to adverse pregnancy and infant outcomes. The role of combined maternal STIs in HIV mother-to-child transmission (MTCT) was evaluated in mother-infant pairs from NICHD HPTN 040. Urine samples from HIV-infected pregnant women during labor were tested by polymerase chain reaction (PCR) for CT, NG, and CMV. Infant HIV infection was determined by serial HIV DNA PCR testing. Maternal syphilis was tested by VDRL and confirmatory treponemal antibodies. A total of 899 mother-infant pairs were evaluated. Over 30% had at least one of the following infections (TP, CT, NG, and/or CMV) detected at the time of delivery. High rates of TP (8.7%), CT (17.8%), NG (4%), and CMV (6.3%) were observed. HIV MTCT was 9.1% (n = 82 infants). HIV MTCT was 12.5%, 10.3%, 11.1%, and 26.3% among infants born to women with CT, TP, NG or CMV respectivel...
Journal of acquired immune deficiency syndromes (1999), Jan 28, 2017
We evaluated HIV drug resistance in adults who received early versus delayed antiretroviral thera... more We evaluated HIV drug resistance in adults who received early versus delayed antiretroviral therapy (ART) in a multi-national trial (HPTN 052, enrollment 2005-2010). In HPTN 052, 1,763 index participants were randomized to start ART at a CD4 cell count of 350-550 cells/mm3 (early ART arm) or <250 cells/mm3 (delayed ART arm). In May 2011, interim study results showed benefit of early ART, and all participants were offered ART regardless of CD4 cell count; the study ended in 2015. Virologic failure was defined as two consecutive viral loads >1,000 copies/mL >24 weeks after ART initiation. Drug resistance testing was performed for pre-treatment (baseline) and failure samples from participants with virologic failure. HIV genotyping results were obtained for 211/249 participants (128 early ART arm; 83 delayed ART arm) with virologic failure. Drug resistance was detected in 4.7% of participants at baseline; 35.5% had new resistance at failure. In univariate analysis, the frequenc...
In occult hepatitis B infection (OBI), hepatitis B virus DNA (HBV DNA) can be detected in serum s... more In occult hepatitis B infection (OBI), hepatitis B virus DNA (HBV DNA) can be detected in serum samples; however, oral fluid collection for detection of HBV DNA has not yet been explored, despite the availability of collection devices. Serum and oral fluid samples from 45 hepatitis B core antibody (anti-HBc)-positive patients were collected for the amplification of the HBV polymerase gene. HBV DNA was detected in five serum and four oral fluid samples (the detection limit for oral fluid was 1.656 log IU/mL in paired serum). In conclusion, simple methodologies of sample collection and in-house polymerase chain reaction (PCR) allowed detection of HBV DNA, and these could be used to improve the diagnosis of OBI, especially in locations with limited resources.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 23, 2017
Congenital Zika virus (ZIKV) syndrome is a newly identified condition resulting from infection du... more Congenital Zika virus (ZIKV) syndrome is a newly identified condition resulting from infection during pregnancy. We analyzed outcome data from a mother-infant cohort in Rio de Janeiro in order to assess whether clinical severity of maternal ZIKV infection was associated with maternal virus load, prior dengue antibodies or abnormal pregnancy/infant outcomes. A clinical severity assessment tool was developed based on duration of fever, severity of rash, multisystem involvement and duration of symptoms during ZIKV infection. ZIKV-RNA load was quantified by PCR cycles in blood/ urine. Dengue IgG antibodies were measured at baseline. Adverse outcomes were defined as fetal loss or a live infant with grossly abnormal clinical or brain imaging findings. Regression models were used to study potential associations. 131 ZIKV-PCR positive pregnant women were scored for clinical disease severity, 6 (4.6%) had mild disease, 98 (74.8%) had moderate disease and 27 (20.6%) severe manifestations of Z...
Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral tr... more Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significan...
Health benefits of postpartum antiretroviral therapy (ART) for human immunodeficiency virus (HIV)... more Health benefits of postpartum antiretroviral therapy (ART) for human immunodeficiency virus (HIV) positive women with high CD4+ T-counts have not been assessed in randomized trials. Asymptomatic, HIV-positive, non-breastfeeding women with pre-ART CD4+ T-cell counts ≥ 400 cells/mm3 started on ART during pregnancy were randomized up to 42 days after delivery to continue or discontinue ART. Lopinavir/ritonavir plus tenofovir/emtricitabine was the preferred ART regimen. The sample size was selected to provide 88% power to detect a 50% reduction from an annualized primary event rate of 2.07%. A post-hoc analysis evaluated HIV/AIDS-related and World Health Organization (WHO) Stage 2 and 3 events. All analyses were intent to treat. 1652 women from 52 sites in Argentina, Botswana, Brazil, China, Haiti, Peru, Thailand and the US were enrolled (1/2010-11/2014). Median age was 28 years and major racial categories were Black African (28%), Asian (25%) White (15%). Median entry CD4 count was 696...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 22, 2017
Cytomegalovirus (CMV) urinary shedding in HIV-infected pregnant women was evaluated to determine ... more Cytomegalovirus (CMV) urinary shedding in HIV-infected pregnant women was evaluated to determine whether it poses an increased risk for congenital CMV infection (cCMV). A subset of mother-infant pairs enrolled in the perinatal NICHD HPTN 040 study (distinguished by no antiretroviral use before labor) was evaluated. Maternal and infant urines were tested by qualitative real-time polymerase chain reaction (RT-PCR) for CMV DNA with quantitative RT-PCR performed on positive specimens. Urine specimens were available for 260 women, 85.4% from the Americas and 14.6% from South Africa. Twenty-four women (9.2%) had detectable CMV viruria by qualitative PCR. Maternal CMV viruria was not associated with mean CD4 cell counts or HIV viral load but was associated with younger maternal age (p=0.02). Overall, ten of 260 infants (3.8%) had cCMV. Women with detectable peripartum CMV viruria were more likely to have infants with cCMV than those without: 20.8% (5/24) versus 2.1% (5/236), (p=0.0001). Wo...
Journal of acquired immune deficiency syndromes (1999), Jan 16, 2016
HIV Prevention Trials Network (HPTN) 052 demonstrated that antiretroviral therapy (ART) prevents ... more HIV Prevention Trials Network (HPTN) 052 demonstrated that antiretroviral therapy (ART) prevents HIV transmission in serodiscordant couples. HIV from index-partner pairs was analyzed to determine the genetic linkage status of partner infections. Forty-six infections were classified as linked, indicating that the index was the likely source of the partner's infection. Lack of viral suppression and higher index viral load were associated with linked infection. Eight linked infections were diagnosed after the index started ART: four near the time of ART initiation and four after ART failure. Linked infections were not observed when the index participant was stably suppressed on ART.
Antiretroviral (ARV) resistance mutations in human immunodeficiency virus type 1 (HIV-1) infectio... more Antiretroviral (ARV) resistance mutations in human immunodeficiency virus type 1 (HIV-1) infection may reduce the efficacy of prophylactic therapy to prevent mother-to-child transmission (PMTCT) and future treatment options. This study evaluated the diversity and the prevalence of transmitted drug resistance (TDR) in protease (PR) and reverse transcriptase (RT) regions of HIV-1 pol gene among 87 ARV-naive HIV-1-infected pregnant women from Rio de Janeiro, Brazil, between 2012 and 2015. The viral diversity comprised HIV-1 subtypes B (67.8%), F1 (17.2%), and C (4.6%); the circulating recombinant forms 12_BF (2.3%), 28/29_BF, 39_BF, 02_AG (1.1% each) and unique recombinants forms (4.5%). The overall prevalence of any TDR was 17.2%, of which 5.7% for nucleoside RT inhibitors, 5.7% for non-nucleoside RT inhibitors, and 8% for PR inhibitors. The TDR prevalence found in this population may affect the virological outcome of the standard PMTCT ARV-regimens, reinforcing the importance of continuous monitoring.
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Papers by Jose Pilotto