Patients with inflammatory arthritis are at increased risk of vaccine preventable infections. This risk is increased by immunomodulatory therapies. Vaccination for influenza and pneumococcal disease reduces the risk. Severe cases of... more
Patients with inflammatory arthritis are at increased risk of vaccine preventable infections. This risk is increased by immunomodulatory therapies. Vaccination for influenza and pneumococcal disease reduces the risk. Severe cases of varicella infection have occurred in patients on biologic therapies. We sought to identify vaccination rates for commonly acquired infections and to ascertain varicella immune status in patients with inflammatory arthritis. 100 patients with inflammatory arthritis were administered a standardised questionnaire. Data collected included age, diagnosis, vaccination history, history of varicella, treatment and the presence of other indications for vaccination. 58 patients (58%) had not received the influenza vaccine in the past year. Only 19 patients (19%) had ever received pneumococcal vaccine. Anti TNF use did not predict vaccination (p = .46). An increasing number of co morbid conditions predicted both pneumococcal (p < 0.003) and influenza vaccine (p ...
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Research Interests: Immunology, Incidence Geometry, Medical Microbiology, Adolescent, Biological Sciences, and 15 moreDenmark, Antiretroviral Therapy, Humans, Female, Male, Incidence, Clinical Sciences, Aged, Adult, Bacteremia, Bacterial meningitis, Clinical Infectious Diseases, Cohort Studies, Medical and Health Sciences, and HIV infections
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Effective vaccines for human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV) remain a significant challenge for these infectious diseases. Given that the innate immune response is key to controlling the scale and nature of... more
Effective vaccines for human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV) remain a significant challenge for these infectious diseases. Given that the innate immune response is key to controlling the scale and nature of developing adaptive immune responses, targeting natural killer (NK) cells that can promote a T-helper type 1 (Th1)-type immune response through the production of interferon-γ (IFNγ) remains an untapped strategic target for improved vaccination approaches. Here, we investigate metabolic and functional responses of NK cells to simian adenovirus prime and MVA boost vaccination in a cohort of healthy volunteers receiving a dual HCV-HIV-1 vaccine. Early and late timepoints demonstrated metabolic changes that contributed to the sustained proliferation of all NK cells. However, a strong impact of human cytomegalovirus (HCMV) on some metabolic and functional responses in NK cells was observed in HCMV seropositive participants. These changes were not restricte...
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The trajectory of immunological and inflammatory changes following acute COVID-19 infection are unclear. We investigate immunological changes in convalescent COVID-19 and interrogate their potential relationships with persistent symptoms,... more
The trajectory of immunological and inflammatory changes following acute COVID-19 infection are unclear. We investigate immunological changes in convalescent COVID-19 and interrogate their potential relationships with persistent symptoms, termed long COVID.We performed paired immunophenotyping at initial SARS-CoV-2 infection and convalescence (n=40, median 68 days) and validated findings in 71 further patients at median 101 days convalescence. Results were compared to 40 pre-pandemic controls. Fatigue and exercise tolerance were assessed and investigated their relationship with convalescent results.We demonstrate persistent expansion of intermediate monocytes, effector CD8+, activated CD4+ and CD8+ T cells, and reduced naïve CD4+ and CD8+ T cells at 68 days, with activated CD8+ T cells remaining increased at 101 days. Patients >60 years also demonstrate reduced naïve CD4+ and CD8+ T cells and expanded activated CD4+ T cells at 101 days. Ill-health, fatigue, and reduced exercise t...
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Background High-cost, high-need users are defined as patients who accumulate large numbers of emergency department visits and hospital admissions that might have been prevented by relatively inexpensive early interventions and primary... more
Background High-cost, high-need users are defined as patients who accumulate large numbers of emergency department visits and hospital admissions that might have been prevented by relatively inexpensive early interventions and primary care. This phenomenon has not been previously described in HIV-infected individuals. Methods We analyzed the health records of HIV-infected individuals using scheduled or unscheduled inpatient or outpatient health care in St James’s Hospital, Dublin, Ireland, from October 2014 to October 2015. Results Twenty-two of 2063 HIV-infected individuals had a cumulative length of stay >30 days in the study period. These individuals accrued 99 emergency department attendances and 1581 inpatient bed days, with a direct cost to the hospital of >€1 million during the study period. Eighteen of 22 had potentially preventable requirements for unscheduled care. Two of 18 had a late diagnosis of HIV. Sixteen of 18 had not been successfully engaged in outpatient HI...
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Research Interests: Clinical Trial, Virology, Medicine, Hepatitis C, HIV, and 5 moreVaccine, Vaccination, Vaccinia Virus, Regimen, and Immunogenicity
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The aim of this study was to compare the immunologic response to a prime-boost immunization strategy combining the 13-valent conjugate pneumococcal vaccine (PCV13) with the 23-valent polysaccharide pneumococcal vaccine (PPSV23) versus the... more
The aim of this study was to compare the immunologic response to a prime-boost immunization strategy combining the 13-valent conjugate pneumococcal vaccine (PCV13) with the 23-valent polysaccharide pneumococcal vaccine (PPSV23) versus the PPSV23 alone in HIV-infected adults. HIV-infected adults were randomized to receive PCV13 at week 0 followed by PPSV23 at week 4 (n = 31, prime-boost group) or PPSV23 alone at week 4 (n = 33, PPSV23-alone group). Serotype specific IgG geometric mean concentration (GMC) and functional oposonophagocytic (OPA) geometric mean titer (GMT) were compared for 12 pneumococcal serotypes shared by both vaccines at week 8 and week 28. The prime-boost vaccine group were more likely to achieve a ≥2-fold increase in IgG GMC and a GMC >1 ug/ml at week 8 (odds ratio (OR) 2.00, 95% confidence interval (CI) 1.46–2.74, p < 0.01) and week 28 (OR 1.95, 95% CI 1.40–2.70, p < 0.01). Similarly, the prime-boost vaccine group were more likely to achieve a ≥4-fold in...
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A retrospective chart review was carried out at the HIV clinic in St. James's Hospital, Dublin to examine the rate of cognitive impairment through the use of surrogate markers for cognitive impairment. 500 consecutive hospital charts... more
A retrospective chart review was carried out at the HIV clinic in St. James's Hospital, Dublin to examine the rate of cognitive impairment through the use of surrogate markers for cognitive impairment. 500 consecutive hospital charts were reviewed. There were 306 men and 194 women. Median age was 37. The most common mode of transmission was heterosexual. 45% had a nadir CD4 < 200. 78.6% were on antiretroviral therapy and 72.26% were virally suppressed. 69/500 patients (13.8%) had one or more positive surrogate markers for cognitive impairment. The surrogate markers used were subjective complaints, a new onset of a psychiatric diagnosis post diagnosis with HIV, neurological complications and radiological evidence of atrophy. Multivariate analysis using logistic regression showed significant relationships only with gender and year of diagnosis. This figure is lower than reported international prevalence rates of cognitive impairment and demonstrates that surrogate markers are n...
Research Interests: Cognition, Adolescent, Medicine, Logistic Regression, Irish medical history, and 15 moreBrain, Humans, Female, Pubmed, Male, Aged, Middle Aged, Cognitive impairment, Adult, Irish Medical History, Nervous System Diseases, Cognition disorders, mass Screening, Medical and Health Sciences, and HIV infections
SummaryThe disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013.... more
SummaryThe disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013–2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late‐stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver‐related deaths from i...
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We read with interest the recent publication by Mendez-Echevarria et al which compared the performance of tuberculin skin tests (TST) with a commercial interferon-γ release assay (IGRA), the QuantiFERON-TB Gold In-Tube assay, for the... more
We read with interest the recent publication by Mendez-Echevarria et al which compared the performance of tuberculin skin tests (TST) with a commercial interferon-γ release assay (IGRA), the QuantiFERON-TB Gold In-Tube assay, for the diagnosis of latent tuberculosis infection (LTBI) and active TB disease (TBD) in children.1 However, we believe several aspects require clarification for readers. Consistent with previous studies evaluating TST and IGRA in children, a significant proportion (4.4%) of participants had indeterminate IGRA results and an even higher proportion (8.9%) had discordant results, which were predominately (38/41; 92.7%) TST+/IGRA−.2 Interestingly, almost all (67/68; 98.5%) children with TBD had concordantly positive …
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These are the guidelines on hepatitis B and C management for IUSTI/WHO in Europe, 2010. They describe the epidemiology, diagnosis, clinical features, treatment and prevention of hepatitis B and C with particular reference to sexual health... more
These are the guidelines on hepatitis B and C management for IUSTI/WHO in Europe, 2010. They describe the epidemiology, diagnosis, clinical features, treatment and prevention of hepatitis B and C with particular reference to sexual health clinical practice.
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This study aimed to determine the rate, cause and management of seizures in the context of potential ART-ASD interactions in a cohort of HIV + individuals. Records of 604 HIV + patients were reviewed and those reporting epilepsy/seizure... more
This study aimed to determine the rate, cause and management of seizures in the context of potential ART-ASD interactions in a cohort of HIV + individuals. Records of 604 HIV + patients were reviewed and those reporting epilepsy/seizure diagnosis were further evaluated. This cohort exhibited a seizure rate of 2.4%. HIV + patients treated for epilepsy displayed low serum ASD levels and failed to achieve seizure control. They were more likely to disengage from Neurology follow-up. For HIV + patients presenting with seizures/epilepsy the ASD prescription and the provision of supplementary support services needs to be carefully considered.
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Anti-retroviral therapy successfully suppresses HIV-1 infection, but fails to provide a cure. During infection Type 1 IFNs normally play an essential role in viral clearance, but in vivo IFN-α only has a modest impact on HIV-1 infection,... more
Anti-retroviral therapy successfully suppresses HIV-1 infection, but fails to provide a cure. During infection Type 1 IFNs normally play an essential role in viral clearance, but in vivo IFN-α only has a modest impact on HIV-1 infection, suggesting its possible targeting by HIV. Here, we report that the HIV protein, Vif, inhibits effective IFN-α signalling via degradation of essential JAK/STAT pathway components. We found that STAT1 and STAT3 are specifically reduced in HEK293T cells expressing Vif and that full length, infectious HIV-1 IIIB strain promotes their degradation in a Vif-dependent manner. HIV-1 IIIB infection of myeloid ThP-1 cells also reduced the IFN-α-mediated induction of the anti-viral gene, ISG15, but not MxA, revealing a functional consequence of this HIV-1-mediated immune evasion strategy. Interestingly, while total STAT levels were not reduced upon in vitro IIIB infection of primary human PBMCs, IFN-α-mediated phosphorylation of STAT1 and STAT3 and ISG inductio...
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The Extension of Community Healthcare Outcomes (ECHO) project is a novel educational intervention designed in New Mexico to transfer subspecialty knowledge about hepatitis C virus (HCV) to primary care providers, thereby increasing... more
The Extension of Community Healthcare Outcomes (ECHO) project is a novel educational intervention designed in New Mexico to transfer subspecialty knowledge about hepatitis C virus (HCV) to primary care providers, thereby increasing patient access to HCV care. The ECHO model has been shown to deliver educational benefits and to result in good treatment outcomes for HCV-infected individuals in the USA; however, this approach has not been assessed in a European setting.We sought to evaluate the feasibility, acceptability and implementation of the ECHO model in Ireland using a pilot study. We present a descriptive review of recruitment, participation, retention and cost of the intervention as well as a qualitative review of the views of participants on the barriers, benefits and acceptability of the ECHO model. In the original Project ECHO in New Mexico, geographical distance posed the greatest barrier to accessing HCV care. In Ireland, people who inject drugs (PWID) were identified by ...
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There is interest in introducing generic antiretroviral drugs (ARVs) into high-income countries in order to maximise efficiency in health care budgets. Studies examining patients’ and providers’ knowledge and attitudes to generic... more
There is interest in introducing generic antiretroviral drugs (ARVs) into high-income countries in order to maximise efficiency in health care budgets. Studies examining patients’ and providers’ knowledge and attitudes to generic substitution in HIV are few. This was a cross-sectional, observational study with a convenience sample of adult HIV-infected patients and health care providers (HCPs). Data on demographics, knowledge of generic medicine and facilitators of generic substitution were collected. Descriptive and univariate analysis was performed using SPSS V.23™. Questionnaires were completed by 66 patients. Seventy-one per cent would have no concerns with the introduction of generic ARVs. An increase in frequency of administration (61%) or pill burden (53%) would make patients less likely to accept generic ARVs. There were 30 respondents to the HCP survey. Concerns included the supply chain of generics, loss of fixed dose combinations, adherence and use of older medications. A...
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Background Human immunodeficiency virus (HIV)-associated neurocognitive disorders occurs in 20%–50% of HIV-positive patients. We undertook this study to assess the prevalence of a positive screen for cognitive impairment in the clinic... more
Background Human immunodeficiency virus (HIV)-associated neurocognitive disorders occurs in 20%–50% of HIV-positive patients. We undertook this study to assess the prevalence of a positive screen for cognitive impairment in the clinic population at our institution and to demonstrate the feasibility of implementing a screening program in routine clinical encounters. Methods This was a cross-sectional study, and patients were recruited prospectively between December 2010 and February 2013. Inclusion criteria were as follows: patients were HIV positive, over the age of 18, capable of giving informed consent, and had sufficient ability to communicate in English. Patients were screened for cognitive impairment using the Brief Neurocognitive Screen. Results A total of 604 patients were recruited, and 51.5% had a positive screen for cognitive impairment. The majority of the study cohort were male (78.8%), mean age was 40.9 (standard deviation, 10.2) years, 70.9% were Irish, the most common...
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Research Interests: Health Economics, Hepatitis C, Ireland, Humans, Liver Cirrhosis, and 15 moreFemale, Male, Hepatocellular Carcinoma, Liver Transplantation, Clinical Sciences, Adult, Cost Benefit Analysis, Cirrhosis, Liver Disease, Cross Sectional Studies, Ambulatory Care, Antiviral Agents, Costs and Cost Analysis, Direct Medical Cost, and Liver neoplasms
Our aim was to assess internal consistency reliability, construct validity, and test-retest reliability of the HDQ with adults living with HIV in Canada and Ireland. We recruited adults 18 years of age or older living with HIV from... more
Our aim was to assess internal consistency reliability, construct validity, and test-retest reliability of the HDQ with adults living with HIV in Canada and Ireland. We recruited adults 18 years of age or older living with HIV from hospital clinics and AIDS service organizations in Canada and Ireland. We administered the HDQ paired with reference measures (World Health Organization Disability Assessment Schedule, SF-36 Questionnaire, Medical Outcomes Study Social Support Survey), and a demographic questionnaire. We calculated HDQ disability presence, severity and episodic scores (scored from 0-100). We calculated Cronbach's alpha and Intraclass Correlation Coefficients (ICC) (Canada only) for the disability severity and episodic scores and considered coefficients >0.80 and >0.70 as acceptable, respectively. To assess construct validity, we tested 40 a priori hypotheses of correlations between scores on the HDQ and reference measures and two known group hypotheses comparing...
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Background The HCV NS3/4A serine protease inhibitors (PIs) boceprevir (BOC), telaprevir (TVR) and simeprevir (SMV) are approved for treatment of chronic hepatitis C infection in combination with pegylated interferon and ribavirin. The... more
Background The HCV NS3/4A serine protease inhibitors (PIs) boceprevir (BOC), telaprevir (TVR) and simeprevir (SMV) are approved for treatment of chronic hepatitis C infection in combination with pegylated interferon and ribavirin. The present study investigated the prevalence of HCV NS3 drug resistance mutations (DRMs) associated with HCV genotype-1-infected individuals at baseline and in viral breakthrough following BOC and TVR treatment. Methods HCV genotype-1-infected individuals were enrolled in a multicentre, prospective outcomes study. The HCV NS3 viral protease was analysed for DRMs at baseline ( n=164) and at viral breakthrough ( n=18) following BOC/ TVR treatment. Results Viral NS3 protease subtype analysis showed 65.2% (107/164) were HCV subtype-1a and 34.8% (57/164) were HCV subtype-1b infections. Naturally occurring PI DRMs in NS3 (V36L, T54S, V55A, Q80K/R and I132V) were identified in 57.3% (94/164) cases at baseline. The NS3 Q80K polymorphism was found in 43/107 (40.2%...
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Research Interests: Epidemiology, Global Health, Hepatitis C, Experience, Humans, and 15 moreDiagnosis, Hepatocellular Carcinoma, Hepatitis C Virus, Liver Transplantation, Incidence, Cohort, Clinical Sciences, HCV, Disease Progression, Cirrhosis, Cost of Illness, chronic hepatitis C, Antiviral Agents, Disease Burden, and mass Screening
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Research Interests: Incidence Geometry, Medical Microbiology, Risk Taking, Medicine, Ireland, and 15 moreSyphilis, Disease Outbreaks, Humans, Female, Sexually transmitted infections, Male, Incidence, Clinical Sciences, Middle Aged, Adult, Public health systems and services research, Sexual Partners, Site testing, High risk, and HIV infections
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In May 2000, public health authorities in Dublin, Ireland, identified a cluster of unexplained severe illness among injecting drug users (IDUs). Similar clusters were also reported in Scotland and England. Concurrent investigations were... more
In May 2000, public health authorities in Dublin, Ireland, identified a cluster of unexplained severe illness among injecting drug users (IDUs). Similar clusters were also reported in Scotland and England. Concurrent investigations were undertaken to identify the aetiology and source of the illnesses. In Dublin, 22 IDUs were identified with injection-site inflammation resulting in hospitalization or death; eight (36%) died. Common clinical findings among patients with severe systemic symptoms included leukaemoid reaction and cardiogenic shock. Seventeen (77%) patients reported injecting heroin intramuscularly in the 2 weeks before illness. Of 11 patients with adequate specimens available for testing, two (18%) were positive by 16S rDNA PCR for Clostridium novyi. Clinical and laboratory findings suggested that histotoxic Clostridia caused a subset of infections in these related clusters. Empiric treatment for infections among IDUs was optimized for anaerobic organisms, and outreach l...
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Background Matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) are central to tissue remodelling during HIV–HCV infection. Here, we assess the potential for antiviral therapy to modulate MMP abundance in THP-1... more
Background Matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) are central to tissue remodelling during HIV–HCV infection. Here, we assess the potential for antiviral therapy to modulate MMP abundance in THP-1 monocyte/macrophages and LX-2 hepatic stellate cells, and in a coinfected patient cohort. Methods THP-1 and LX-2 cells were treated with ribavirin (RBV)/interferon-α (IFN-α) and select HIV antivirals. Venous blood was reserved from HIV–HCV-coinfected patients, HIV- and HCV-monoinfected patients, and healthy controls, with the HIV–HCV cohort being sampled again at day 3 and 14 subsequent to the start of combination therapy with RBV/pegylated IFN-α. Samples were subjected to gelatin zymography, real-time RT-PCR and/or ELISA, where appropriate. Results RBV/IFN-α decreased MMP-9 activity, and increased MMP-9 mRNA and protein expression in THP-1 cells, but not in LX-2 cells. Decreases in MMP-9 activity were mediated by IFN-α, which also attenuated RBV in...