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HIV Seropositivity: HELP
Articles from Imperial College School of Medicine
Based on 30 articles published since 2009

These are the 30 published articles about HIV Seropositivity that originated from Imperial College School of Medicine during 2009-2019.
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Position statement on the use of antiretroviral therapy to reduce HIV transmission, January 2013: the British HIV Association (BHIVA) and the Expert Advisory Group on AIDS (EAGA). 2013

Fidler, S / Anderson, J / Azad, Y / Delpech, V / Evans, C / Fisher, M / Gazzard, B / Gill, N / Lazarus, L / Lowbury, R / Orton, K / Osoro, B / Radcliffe, K / Smith, B / Churchill, D / Rogstad, K / Cairns, G. ·Imperial College London, London, UK. s.fidler@imperial.ac.uk ·HIV Med · Pubmed #23489936.

ABSTRACT: -- No abstract --

2 Editorial Testing times for HIV. 2013

Weber, Jonathan / Tatoud, Roger. ·Wright-Fleming Institute, Faculty of Medicine, Imperial College London W2 1PG, UK. ·BMJ · Pubmed #24048300.

ABSTRACT: -- No abstract --

3 Review Efficacy of HIV Postexposure Prophylaxis: Systematic Review and Meta-analysis of Nonhuman Primate Studies. 2015

Irvine, Cadi / Egan, Kieren J / Shubber, Zara / Van Rompay, Koen K A / Beanland, Rachel L / Ford, Nathan. ·Department of HIV/AIDS, World Health Organization. · Department of Mental Health and Psychiatry, University Hospitals of Geneva, Switzerland. · Department of Infectious Disease Epidemiology, Imperial College London, United Kingdom. · California National Primate Research Center, University of California, Davis. ·Clin Infect Dis · Pubmed #25972498.

ABSTRACT: BACKGROUND: The efficacy of antiretrovirals as postexposure prophylaxis (PEP) to prevent viral acquisition was demonstrated in nonhuman primate models of human immunodeficiency virus (HIV) in the early 1990s. To complement the evidence base for efficacy of HIV PEP in humans, we systematically reviewed the published data on PEP efficacy across animal studies. METHODS: PubMed, Web of Science, and Embase were searched from inception to 31 May 2014 for randomized and nonrandomized studies reporting seroconversions among uninfected animals exposed to HIV or simian immunodeficiency virus, irrespective of route of exposure. Seroconversion risk data were pooled using random-effects models, and associations explored through meta-regression. RESULTS: Twenty-five studies (408 primates) were included for review. The risk of serconversion was 89% lower among animals exposed to PEP compared with those that did not receive PEP (odds ratio, 0.11 [95% confidence interval, .05-.23]). Heterogeneity was low (I(2) = 0.0%). In meta-regression, a significant association was found between timing of PEP and seroconversion and the use of tenofovir compared with other drugs. CONCLUSIONS: This review provides further evidence of the protective benefit of PEP in preventing HIV acquisition, and the importance of initiating PEP as early as possible following virus exposure.

4 Review Low levels of HIV test coverage in clinical settings in the U.K.: a systematic review of adherence to 2008 guidelines. 2014

Elmahdi, Rahma / Gerver, Sarah M / Gomez Guillen, Gabriela / Fidler, Sarah / Cooke, Graham / Ward, Helen. ·Department of Infectious Disease Epidemiology, Imperial College London, , London, UK. ·Sex Transm Infect · Pubmed #24412996.

ABSTRACT: OBJECTIVES: To quantify the extent to which guideline recommendations for routine testing for HIV are adhered to outside of genitourinary medicine (GUM), sexual health (SH) and antenatal clinics. METHODS: A systematic review of published data on testing levels following publication of 2008 guidelines was undertaken. Medline, Embase and conference abstracts were searched according to a predefined protocol. We included studies reporting the number of HIV tests administered in those eligible for guideline recommended testing. We excluded reports of testing in settings with established testing surveillance (GUM/SH and antenatal clinics). A random effects meta-analysis was carried out to summarise level of HIV testing across the studies identified. RESULTS: Thirty studies were identified, most of which were retrospective studies or audits of testing practice. Results were heterogeneous. The overall pooled estimate of HIV test coverage was 27.2% (95% CI 22.4% to 32%). Test coverage was marginally higher in patients tested in settings where routine testing is recommended (29.5%) than in those with clinical indicator diseases (22.4%). Provider test offer was found to be lower (40.4%) than patient acceptance of testing (71.5%). CONCLUSIONS: Adherence to 2008 national guidelines for HIV testing in the UK is poor outside of GUM/SH and antenatal clinics. Low levels of provider test offer appear to be a major contributor to this. Failure to adhere to testing guidelines is likely to be contributing to late diagnosis with implications for poorer clinical outcomes and continued onwards transmission of HIV. Improved surveillance of HIV testing outside of specialist settings may be useful in increasing adherence testing guidelines.

5 Article Completion of isoniazid preventive therapy among human immunodeficiency virus positive adults in urban Malawi. 2018

Thindwa, D / MacPherson, P / Choko, A T / Khundi, M / Sambakunsi, R / Ngwira, L G / Kalua, T / Webb, E L / Corbett, E L. ·Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi, Department of Infectious Disease Epidemiology, Imperial College London, London. · Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, Department of Public Health and Policy, University of Liverpool, Liverpool. · Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi, Infectious Disease Epidemiology Department, London School of Hygiene & Tropical Medicine (LSHTM), London, UK. · Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi. · Department of HIV/AIDS, Ministry of Health, Lilongwe, Malawi. · Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi, Clinical Research Department, LSHTM, London, UK. ·Int J Tuberc Lung Dis · Pubmed #29471904.

ABSTRACT: SETTING: Despite worldwide scale-up of human immunodeficiency virus (HIV) care services, relatively few countries have implemented isoniazid preventive therapy (IPT). Among other programmatic concerns, IPT completion tends to be low, especially when not fully integrated into HIV care clinics. OBJECTIVE: To estimate non-completion of 6-month IPT and its predictors among HIV-positive adults aged 16 years. DESIGN: A prospective cohort study nested within a cluster-randomised trial of TB prevention was conducted between February 2012 and June 2014. IPT for 6 months was provided with pyridoxine at study clinics. Non-completion was defined as loss to follow-up (LTFU), death, active/presumptive TB or stopping IPT for any other reason. Random-effects logistic regression was used to determine predictors of non-completion. RESULTS: Of 1284 HIV-positive adults initiated on IPT, 885/1280 (69.1%) were female; the median CD4 count was 337 cells/μl (IQR 199-511); 320 (24.9%) did not complete IPT. After controlling for antiretroviral treatment status, IPT initiation year, age and sex, non-completion of IPT was associated with World Health Organization stage 3/4 (aOR 1.76, 95%CI 1.22-2.55), CD4 count 100-349 cells/μl (aOR 1.93, 95%CI 1.10-3.38) and any reported side effects (aOR 22.00, 95%CI 9.45-46.71). CONCLUSION: Completion of IPT was suboptimal. Interventions to further improve retention should target immunosuppressed HIV-positive adults and address side effects.

6 Article Differences in risk behaviours and HIV status between primary amphetamines and opioid injectors in Estonia and Russia. 2018

Tavitian-Exley, Isabel / Maheu-Giroux, Mathieu / Platt, Lucy / Heimer, Robert / Uusküla, Anneli / Levina, Olga / Vickerman, Peter / Boily, Marie-Claude. ·Department of Infectious Disease Epidemiology, Imperial College London, United Kingdom. Electronic address: TavitianExley@gmail.com. · Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montréal, Canada. · Department of Social and Environmental Health Research, London School of Hygiene and Tropical Medicine, United Kingdom. · Epidemiology of Microbial Diseases, School of Public Health, Yale University, United States. · Department of Family Medicine and Public Health, University of Tartu, Tartu, Estonia. · NGO Stellit, St Petersburg, Russian Federation. · School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom. · Department of Infectious Disease Epidemiology, Imperial College London, United Kingdom. Electronic address: mc.boily@imperial.ac.uk. ·Int J Drug Policy · Pubmed #29306786.

ABSTRACT: BACKGROUND AND OBJECTIVE: People who inject drugs (PWID) account for over half of new HIV infections in Eastern Europe and central Asia, where opioids continue to be the dominant illicit drugs injected. Stimulants including amphetamines (ATS) have been associated with HIV infection risk in several settings. We sought to examine whether primary ATS injection was associated with greater HIV risk, compared to opioid injection in two European locales with significant HIV epidemics. METHODS: PWID in Kohtla-Järve and St. Petersburg were recruited using respondent-driven sampling in 2012-2013. Survey data on demographic characteristics, service use, injecting and sexual risk behaviours and HIV-status (and HCV in Kohtla-Järve) were compared between primary opioid and ATS injectors using logistic regression models. RESULTS: Of 591 injectors recruited in Kohtla-Järve and 811 in St. Petersburg, 195 (33%) and 27 (4%) primarily injected ATS in each city. In both cities, ATS injectors were younger than opioid injectors, initiated injection later, injected less frequently and were more likely to have been paid for sex. In both cities, PWID had high levels of multiple sex partners. In Kohtla-Järve, ATS-injectors had lower odds of back-loading and greater odds of polydrug use than opioid-injectors. In St. Petersburg, where over half of PWID reported unsafe sharing practices, ATS-injectors were less likely to report these practices. ATS-injection was negatively associated with being HIV positive in Kohtla-Järve (aOR = 0.6; 95%CI: 0.5-0.8) and St. Petersburg (aOR = 0.3; 95%CI: 0.1-0.7). ATS-injection was negatively associated with HCV-reactivity in Kohtla-Järve (aOR = 0.5; 95%CI: 0.3-0.6). CONCLUSIONS: In both locations, primary ATS injection was associated with lower injecting risk behaviours, lower odds of HIV and being paid for sex compared to opioid injection. Interventions targeting the characteristics and needs of ATS injectors are needed to increase contact with services and reduce sexual and injecting risk. Harm reduction services, including sexual risk reduction, need to be expanded for all PWID in St. Petersburg.

7 Article Differences in health-related quality of life between HIV-positive and HIV-negative people in Zambia and South Africa: a cross-sectional baseline survey of the HPTN 071 (PopART) trial. 2017

Thomas, Ranjeeta / Burger, Ronelle / Harper, Abigail / Kanema, Sarah / Mwenge, Lawrence / Vanqa, Nosivuyile / Bell-Mandla, Nomtha / Smith, Peter C / Floyd, Sian / Bock, Peter / Ayles, Helen / Beyers, Nulda / Donnell, Deborah / Fidler, Sarah / Hayes, Richard / Hauck, Katharina / Anonymous2810921. ·Department of Infectious Disease Epidemiology, Imperial College London, London, UK. Electronic address: ranjeeta.thomas@imperial.ac.uk. · Department of Economics, Stellenbosch University, Stellenbosch, South Africa. · Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa. · ZAMBART Project, Ridgeway Campus, University of Zambia, Lusaka, Zambia. · Imperial College Business School, Imperial College London, London, UK. · Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK. · Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK. · Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. · Department of Medicine, Imperial College London, London, UK. · Department of Infectious Disease Epidemiology, Imperial College London, London, UK. ·Lancet Glob Health · Pubmed #28964756.

ABSTRACT: BACKGROUND: The life expectancy of HIV-positive individuals receiving antiretroviral therapy (ART) is approaching that of HIV-negative people. However, little is known about how these populations compare in terms of health-related quality of life (HRQoL). We aimed to compare HRQoL between HIV-positive and HIV-negative people in Zambia and South Africa. METHODS: As part of the HPTN 071 (PopART) study, data from adults aged 18-44 years were gathered between Nov 28, 2013, and March 31, 2015, in large cross-sectional surveys of random samples of the general population in 21 communities in Zambia and South Africa. HRQoL data were collected with a standardised generic measure of health across five domains. We used β-distributed multivariable models to analyse differences in HRQoL scores between HIV-negative and HIV-positive individuals who were unaware of their status; aware, but not in HIV care; in HIV care, but who had not initiated ART; on ART for less than 5 years; and on ART for 5 years or more. We included controls for sociodemographic variables, herpes simplex virus type-2 status, and recreational drug use. FINDINGS: We obtained data for 19 750 respondents in Zambia and 18 941 respondents in South Africa. Laboratory-confirmed HIV status was available for 19 330 respondents in Zambia and 18 004 respondents in South Africa; 4128 (21%) of these 19 330 respondents in Zambia and 4012 (22%) of 18 004 respondents in South Africa had laboratory-confirmed HIV. We obtained complete HRQoL information for 19 637 respondents in Zambia and 18 429 respondents in South Africa. HRQoL scores did not differ significantly between individuals who had initiated ART more than 5 years previously and HIV-negative individuals, neither in Zambia (change in mean score -0·002, 95% CI -0·01 to 0·001; p=0·219) nor in South Africa (0·000, -0·002 to 0·003; p=0·939). However, scores did differ between HIV-positive individuals who had initiated ART less than 5 years previously and HIV-negative individuals in Zambia (-0·006, 95% CI -0·008 to -0·003; p<0·0001). A large proportion of people with clinically confirmed HIV were unaware of being HIV-positive (1768 [43%] of 4128 people in Zambia and 2026 [50%] of 4012 people in South Africa) and reported good HRQoL, with no significant differences from that of HIV-negative people (change in mean HRQoL score -0·001, 95% CI -0·003 to 0·001, p=0·216; and 0·001, -0·001 to 0·001, p=0·997, respectively). In South Africa, HRQoL scores were lower in HIV-positive individuals who were aware of their status but not enrolled in HIV care (change in mean HRQoL -0·004, 95% CI -0·01 to -0·001; p=0·010) and those in HIV care but not on ART (-0·008, -0·01 to -0·004; p=0·001) than in HIV-negative people, but the magnitudes of difference were small. INTERPRETATION: ART is successful in helping to reduce inequalities in HRQoL between HIV-positive and HIV-negative individuals in this general population sample. These findings highlight the importance of improving awareness of HIV status and expanding ART to prevent losses in HRQoL that occur with untreated HIV progression. The gains in HRQoL after individuals initiate ART could be substantial when scaled up to the population level. FUNDING: National Institute of Allergy and Infectious Diseases, National Institute on Drug Abuse, National Institute of Mental Health, President's Emergency Plan for AIDS Relief, International Initiative for Impact Evaluation, the Bill & Melinda Gates Foundation.

8 Article Terminal differentiation of T cells is strongly associated with CMV infection and increased in HIV-positive individuals on ART and lifestyle matched controls. 2017

Booiman, Thijs / Wit, Ferdinand W / Girigorie, Arginell F / Maurer, Irma / De Francesco, Davide / Sabin, Caroline A / Harskamp, Agnes M / Prins, Maria / Franceschi, Claudio / Deeks, Steven G / Winston, Alan / Reiss, Peter / Kootstra, Neeltje A / Anonymous1540916. ·Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands. · Department of Global Health & Division of Infectious Disease, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · HIV Monitoring Foundation, Amsterdam, The Netherlands. · Department of Infection and Population Health, University College London, London, United Kingdom. · Public health service, Amsterdam, The Netherlands. · Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum Universita di Bologna, Bologna, Italy. · Department of Medicine, University of California, San Francisco, California, United States of America. · Imperial College of Science, Technology and Medicine, London, United Kingdom. ·PLoS One · Pubmed #28806406.

ABSTRACT: HIV-1-positive individuals on successful antiretroviral therapy (ART) are reported to have higher rates of age-associated non-communicable comorbidities (AANCCs). HIV-associated immune dysfunction has been suggested to contribute to increased AANCC risk. Here we performed a cross-sectional immune phenotype analysis of T cells in ART-treated HIV-1-positive individuals with undetectable vireamia (HIV-positives) and HIV-1-negative individuals (HIV-negatives) over 45 years of age. In addition, two control groups were studied: HIV negative adults selected based on lifestyle and demographic factors (Co-morBidity in Relation to AIDS, or COBRA) and unselected age-matched donors from a blood bank. Despite long-term ART (median of 12.2 years), HIV-infected adults had lower CD4+ T-cell counts and higher CD8+ T-cell counts compared to well-matched HIV-negative COBRA participants. The proportion of CD38+HLA-DR+ and PD-1+ CD4+ T-cells was higher in HIV-positive cohort compared to the two HIV-negative cohorts. The proportion CD57+ and CD27-CD28- cells of both CD4+ and CD8+ T-cells in HIV-positives was higher compared to unselected adults (blood bank) as reported before but this difference was not apparent in comparison with well-matched HIV-negative COBRA participants. Multiple regression analysis showed that the presence of an increased proportion of terminally differentiated T cells was strongly associated with CMV infection. Compared to appropriately selected HIV-negative controls, HIV-positive individuals on ART with long-term suppressed viraemia exhibited incomplete immune recovery and increased immune activation/exhaustion. CMV infection rather than treated HIV infection appears to have more consistent effects on measures of terminal differentiation of T cells.

9 Article Viral genetic variation accounts for a third of variability in HIV-1 set-point viral load in Europe. 2017

Blanquart, François / Wymant, Chris / Cornelissen, Marion / Gall, Astrid / Bakker, Margreet / Bezemer, Daniela / Hall, Matthew / Hillebregt, Mariska / Ong, Swee Hoe / Albert, Jan / Bannert, Norbert / Fellay, Jacques / Fransen, Katrien / Gourlay, Annabelle J / Grabowski, M Kate / Gunsenheimer-Bartmeyer, Barbara / Günthard, Huldrych F / Kivelä, Pia / Kouyos, Roger / Laeyendecker, Oliver / Liitsola, Kirsi / Meyer, Laurence / Porter, Kholoud / Ristola, Matti / van Sighem, Ard / Vanham, Guido / Berkhout, Ben / Kellam, Paul / Reiss, Peter / Fraser, Christophe / Anonymous3151039. ·Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom. · Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom. · Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam, the Netherlands. · Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom. · Stichting HIV Monitoring, Amsterdam, the Netherlands. · Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. · Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden. · Division for HIV and other Retroviruses, Robert Koch Institute, Berlin, Germany. · School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. · Swiss Institute of Bioinformatics, Lausanne, Switzerland. · HIV/STI reference laboratory, WHO collaborating centre, Institute of Tropical Medicine, Department of Clinical Science, Antwerpen, Belgium. · Department of Infection and Population Health, University College London, London, United Kingdom. · Department of Epidemiology, John Hopkins University, Baltimore, Maryland, United States of America. · Department of Infectious Disease Epidemiology, Robert Koch-Institute, Berlin, Germany. · Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland. · Institute of Medical Virology, University of Zurich, Zurich, Switzerland. · Department of Infectious Diseases, Helsinki University Hospital, Helsinki, Finland. · Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Baltimore, Maryland, United States of America. · Department of Health Security, National Institute for Health and Welfare, Helsinki, Finland. · INSERM CESP U1018, Université Paris Sud, Université Paris Saclay, APHP, Service de Santé Publique, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France. · Virology Unit, Immunovirology Research Pole, Biomedical Sciences Department, Institute of Tropical Medicine, Antwerpen, Belgium. · Kymab Ltd, Cambridge, United Kingdom. · Division of Infectious Diseases, Department of Medicine, Imperial College London, London, United Kingdom. · Department of Global Health, Academic Medical Center, Amsterdam, the Netherlands. ·PLoS Biol · Pubmed #28604782.

ABSTRACT: HIV-1 set-point viral load-the approximately stable value of viraemia in the first years of chronic infection-is a strong predictor of clinical outcome and is highly variable across infected individuals. To better understand HIV-1 pathogenesis and the evolution of the viral population, we must quantify the heritability of set-point viral load, which is the fraction of variation in this phenotype attributable to viral genetic variation. However, current estimates of heritability vary widely, from 6% to 59%. Here we used a dataset of 2,028 seroconverters infected between 1985 and 2013 from 5 European countries (Belgium, Switzerland, France, the Netherlands and the United Kingdom) and estimated the heritability of set-point viral load at 31% (CI 15%-43%). Specifically, heritability was measured using models of character evolution describing how viral load evolves on the phylogeny of whole-genome viral sequences. In contrast to previous studies, (i) we measured viral loads using standardized assays on a sample collected in a strict time window of 6 to 24 months after infection, from which the viral genome was also sequenced; (ii) we compared 2 models of character evolution, the classical "Brownian motion" model and another model ("Ornstein-Uhlenbeck") that includes stabilising selection on viral load; (iii) we controlled for covariates, including age and sex, which may inflate estimates of heritability; and (iv) we developed a goodness of fit test based on the correlation of viral loads in cherries of the phylogenetic tree, showing that both models of character evolution fit the data well. An overall heritability of 31% (CI 15%-43%) is consistent with other studies based on regression of viral load in donor-recipient pairs. Thus, about a third of variation in HIV-1 virulence is attributable to viral genetic variation.

10 Article Relapse of HHV8-positive multicentric Castleman disease following rituximab-based therapy in HIV-positive patients. 2017

Pria, Alessia Dalla / Pinato, David / Roe, Jennifer / Naresh, Kikeri / Nelson, Mark / Bower, Mark. ·Department of Oncology, The Chelsea and Westminster Hospital, London, United Kingdom. · Department of HIV Medicine, The Chelsea and Westminster Hospital, London, United Kingdom; and. · Department of Pathology, Imperial College School of Medicine, London, United Kingdom. ·Blood · Pubmed #28143881.

ABSTRACT: Successful treatment of HIV-associated multicentric Castleman disease (HIV+MCD) with rituximab-based approaches has dramatically improved survival and reduced the risk of human herpesvirus 8 (HHV8)-associated lymphoma. Longer term outcomes including relapse rates have not been described and are important to establish the potential role of maintenance therapy. A prospective cohort of 84 patients with biopsy-proven HIV+MCD were treated with risk-stratified rituximab-based therapy. Four patients (5%) died of refractory HIV+MCD and 80 achieved clinical remission. The median follow-up for the 80 patients was 6.9 years and their 5-year overall survival was 92% (95% confidence interval [CI], 85 to 99). Eighteen have relapsed (all histologically confirmed), including 5 with concomitant HHV8-associated lymphoma and MCD at relapse. The 5-year relapse-free survival is 82% (95% CI, 72 to 92). No clinical or laboratory findings that were present at MCD diagnosis predicted subsequent relapse, and the median time to first relapse was 30 months (maximum, 10 years). There were no significant differences in clinicopathological features at initial diagnosis and at relapse. All patients were successfully retreated at relapse with rituximab-based therapy. Only 1 patient died of relapsed MCD (at fifth relapse 9.4 years after initial diagnosis). Despite the use of rituximab, the risk of developing HHV8-associated lymphoma was significantly elevated in this cohort, with an incidence of 11.4/1000 person-years. The relatively low relapse rate and high salvage rates at relapse reduce the potential benefit of maintenance therapy; this should only be advocated in the context of a clinical trial.

11 Article HCV reinfection incidence and spontaneous clearance rates in HIV-positive men who have sex with men in Western Europe. 2017

Ingiliz, Patrick / Martin, Thomas C / Rodger, Alison / Stellbrink, Hans-Jürgen / Mauss, Stefan / Boesecke, Christoph / Mandorfer, Mattias / Bottero, Julie / Baumgarten, Axel / Bhagani, Sanjay / Lacombe, Karine / Nelson, Mark / Rockstroh, Jürgen K / Anonymous8050881. ·Center for Infectiology (CIB), Berlin, Germany. Electronic address: ingiliz@zibp.de. · Chelsea and Westminster Hospital, London, United Kingdom. · The Royal Free Hospital, London, United Kingdom. · Infectiology Center Hamburg (ICH), Hamburg, Germany. · Center for HIV and Hepatogastroenterology, Duesseldorf, Germany. · University of Bonn, Department of Medicine I, Bonn, Germany. · Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. · Service des maladies infectieuses et tropicales, Hôpital Saint-Antoine, AP-HP, France. · Center for Infectiology (CIB), Berlin, Germany. · Service des maladies infectieuses et tropicales, Hôpital Saint-Antoine, AP-HP, France; Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), Paris, France. · Chelsea and Westminster Hospital, London, United Kingdom; Imperial College School of Medicine, London, United Kingdom. ·J Hepatol · Pubmed #27650285.

ABSTRACT: BACKGROUND & AIMS: Moderate cure rates of acute hepatitis C virus (HCV) infections with pegylated interferon and ribavirin have been described in the last decade in men who have sex with men (MSM), who are also coinfected with the human immunodeficiency virus (HIV). However, a subsequent high incidence of HCV reinfections has been reported regionally in men who both clear the infection spontaneously or who respond to treatment. METHODS: Retrospective analysis of reinfections in HIV infected MSM in eight centers from Austria, France, Germany, and the UK within the NEAT network between May 2002 and June 2014. RESULTS: Of 606 individuals who cleared HCV spontaneously or were successfully treated, 149 (24.6%) presented with a subsequent HCV reinfection. Thirty out of 70 (43%) who cleared again or were successfully treated, presented with a second reinfection, 5 with a third, and one with a fourth reinfection. The reinfection incidence was 7.3/100 person-years (95% CI 6.2-8.6). We found a trend for lower incidence among individuals who had spontaneously cleared their incident infection than among individuals who were treated (Hazard ratio 0.62, 95% CI 0.38-1.02, p=0.06). Spontaneous clearance of reinfection was associated with ALT levels >1000IU/ml and spontaneous clearance of a prior infection. CONCLUSIONS: HCV reinfection is an issue of major concern in HIV-positive MSM. Prevention strategies are needed for high risk groups to reduce morbidity and treatment costs. HIV-positive MSM with a prior HCV infection should be tested every 3 to 6months for reinfection. Those who had achieved a reinfection should be tested every 3months. LAY SUMMARY: We evaluated the occurrence of HCV reinfection in HIV-positive men who have sex with men. We found an alarming incidence of 7.3/100 person-years. Prevention measures need to address this specific subgroup of patients at high risk for HCV.

12 Article Migration as a risk and a livelihood strategy: HIV across the life course of migrant families in India. 2017

Rai, Tanvi / Lambert, Helen S / Ward, Helen. ·a School of Public Health , Imperial College London , London , UK. · b School of Social and Community Medicine , University of Bristol , Bristol , UK. ·Glob Public Health · Pubmed #27002744.

ABSTRACT: Migrant workers are understood to be vulnerable to HIV. However, little is known about the experience of migration-based households following HIV infection. This qualitative study examined the migration-HIV relationship beyond the point of infection, looking at how it affects livelihood choices, household relationships and the economic viability of migrant families. We conducted semi-structured interviews with 33 HIV-positive migrant men and women recruited from an anti-retroviral therapy (ART) centre in north India. Following infection among the migrant men, contact with free, public-sector HIV services was often made late, after the development of debilitating symptoms, abandonment of migrant work and return to native villages. After enrolment at the ART centre participants' health eventually stabilised but they now faced serious economic debt, an inflexible treatment regimen and reduced physical strength. Insecure migrant job markets, monthly drug collection and discriminatory employment policies impeded future migration plans. HIV-positive wives of migrants occupied an insecure position in the rural marital household that depended on their husbands' health and presence of children. The migration-HIV relationship continued to shape the life course of migrant families beyond the point of infection, often exposing them again to the economic insecurity that migration had helped to overcome, threatening their long-term survival.

13 Article Defining cognitive impairment in people-living-with-HIV: the POPPY study. 2016

De Francesco, Davide / Underwood, Jonathan / Post, Frank A / Vera, Jaime H / Williams, Ian / Boffito, Marta / Sachikonye, Memory / Anderson, Jane / Mallon, Patrick W G / Winston, Alan / Sabin, Caroline A / Anonymous230886. ·Research Department of Infection & Population Health, UCL - Royal Free Campus, London, UK. d.defrancesco@ucl.ac.uk. · Division of Infectious Diseases, Imperial College London, London, UK. · King's College London, London, UK. · Brighton and Sussex Medical School, Brighton, UK. · Mortimer Market Centre, UCL, London, UK. · Chelsea and Westminster Healthcare NHS Foundation Trust, London, UK. · UK Community Advisory Board, London, UK. · Homerton University Hospital, London, UK. · UCD School Of Medicine, Dublin, Ireland. · Research Department of Infection & Population Health, UCL - Royal Free Campus, London, UK. ·BMC Infect Dis · Pubmed #27793128.

ABSTRACT: BACKGROUND: The reported prevalence of cognitive impairment (CI) varies widely in cohorts of people living with HIV (PLWH); this may partly be due to the use of different diagnostic criteria. Agreement between diagnostic criteria of CI, the optimal definition to use, and associations with patient-reported cognitive symptoms have not been fully investigated. METHODS: Two hundred ninety PLWH aged >50 years and 97 matched negative controls completed a detailed assessment of cognitive function and three questions regarding cognitive symptoms. Age- and education-adjusted test scores (T-scores) determined if subjects met the following definitions of CI: Frascati, global deficit score (GDS) and the multivariate normative comparison (MNC) method. RESULTS: PLWH were more likely than controls to meet each definition of CI (ORs were 2.17, 3.12 and 3.64 for Frascati, GDS and MNC, respectively). Agreement of MNC with Frascati and GDS was moderate (Cohen's k = 0.42 and 0.48, respectively), whereas that between Frascati and GDS was good (k = 0.74). A significant association was found between all the three criteria and reporting of memory loss but not with attention and reasoning problems. The 41 (14 %) PLWH meeting all the three criteria had the lowest median global T-score (36.9) and highest rate of symptom reporting (42 %). CONCLUSIONS: Different CI criteria show fair diagnostic agreement, likely reflecting their ability to exclude CI in the same group of individuals. Given the lower overall cognitive performance and higher rates of symptom reporting in those meeting all three criteria of CI, further work assessing this as a definition of CI in PLWH is justified.

14 Article Neurocognitive Function and Neuroimaging Markers in Virologically Suppressed HIV-positive Patients Randomized to Ritonavir-boosted Protease Inhibitor Monotherapy or Standard Combination ART: A Cross-sectional Substudy From the PIVOT Trial. 2016

Arenas-Pinto, Alejandro / Stöhr, Wolfgang / Jäger, Hans Rolf / Haddow, Lewis / Clarke, Amanda / Johnson, Margaret / Chen, Fabian / Winston, Alan / Godi, Claudia / Thust, Steffi / Trombin, Rita / Cairns, Janet / Solanky, Bhavana S / Golay, Xavier / Paton, Nicholas I / Anonymous7070866. ·MRC-Clinical Trials Unit at University College London (UCL) UCL Research Department of Infection and Population Health. · MRC-Clinical Trials Unit at University College London (UCL). · Neuroradiology Academic Unit, UCL Department of Brain Repair & Rehabilitation, Institute of Neurology. · UCL Research Department of Infection and Population Health. · Brighton and Sussex University Hospitals NHS Trust, Brighton. · Royal Free Hospital, London. · Royal Berkshire Hospital, Reading. · Imperial College London, United Kingdom. · NMR Research Unit, UCL Department of Neuroinflammation, Queen Square MS Centre, Institute of Neurology, London. · MRC-Clinical Trials Unit at University College London (UCL) Yong Loo Lin School of Medicine, National University of Singapore, Singapore. ·Clin Infect Dis · Pubmed #27143662.

ABSTRACT: BACKGROUND: To determine whether treatment with ritonavir-boosted protease inhibitor (PI) monotherapy is associated with detrimental effects on neurocognitive function or brain imaging markers compared to standard antiretroviral therapy (ART). METHODS: Neuropsychological assessment and brain magnetic resonance imaging were performed at the last study visit in a subset of participants randomized to PI monotherapy (PI-mono group) or ongoing triple ART (OT group) in the PIVOT trial. We calculated a global z-score (NPZ-7) from the average of the individual test z-scores and the proportion of participants with symptomatic neurocognitive impairment (score >1 standard deviation below normative means in ≥2 cognitive domains and neurocognitive symptoms). In a subgroup, white matter hyperintensities, bicaudate index, global cortical (GCA) and medial temporal lobe atrophy scores and single voxel (basal ganglia) N-acetylaspartate (NAA)/Choline, NAA/Creatine and myo-inositol/Creatine ratios were measured. RESULTS: 146 participants (75 PI-mono) had neurocognitive testing (median time after randomization 3.8 years), of whom 78 were imaged. We found no difference between arms in NPZ-7 score (median -0.4 (interquartile range [IQR] = -0.7; 0.1) vs -0.3 (IQR = -0.7; 0.3) for the PI-mono and OT groups respectively, P = .28), the proportion with symptomatic neurocognitive impairment (13% and 18% in the PI-mono and OT groups respectively; P = .41), or any of the neuroimaging variables (P > .05). Symptomatic neurocognitive impairment was associated with higher GCA score (OR = 6.2 per additional score; 95% confidence interval, 1.7-22.3 P = .005) but no other imaging variables. CONCLUSIONS: Based on a comprehensive neuropsychological assessment and brain imaging, PI monotherapy does not increase the risk of neurocognitive impairment in stable human immunodeficiency virus-positive patients.

15 Article Predictive value of prostate specific antigen in a European HIV-positive cohort: does one size fit all? 2016

Shepherd, Leah / Borges, Álvaro H / Ravn, Lene / Harvey, Richard / Bower, Mark / Grulich, Andrew / Silverberg, Michael / Kronborg, Gitte / Galli, Massimo / Kirk, Ole / Lundgren, Jens / Mocroft, Amanda / Anonymous5560856. ·Research Department of Infection and Population Health, University College London, London, UK. · Centre for Health & Infectious Disease Research (CHIP), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. · Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark. · Charing Cross Oncology Laboratory and Trophoblastic Disease Centre, Charing Cross Hospital Campus of Imperial College Healthcare National Health Service Trust, London, UK. · National Centre for HIV Malignancy, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK. · Kirby Institute, The University of New South Wales, Sydney, NSW, Australia. · Kaiser Permanente Northern California, Oakland, CA, USA. · Institut for Klinisk Medicin, Hvidovre Hospital, Hvidovre, Denmark. · Clinic of Infectious Disease, Luigi Sacco Hospital, Milan, Italy. ·Antivir Ther · Pubmed #26823399.

ABSTRACT: BACKGROUND: It is common practice to use prostate specific antigen (PSA) ≥4.0 ng/ml as a clinical indicator for men at risk of prostate cancer (PCa), however, this is unverified in HIV+ men. We aimed to describe kinetics and predictive value of PSA for PCa in HIV+ men. METHODS: A nested case control study of 21 men with PCa and 40 matched-controls within EuroSIDA was conducted. Prospectively stored plasma samples before PCa (or matched date in controls) were measured for the following markers: total PSA (tPSA), free PSA (fPSA), testosterone and sex hormone binding globulin (SHBG). Conditional logistic regression models investigated associations between markers and PCa. Mixed models were used to describe kinetics. Sensitivity and specificity of using tPSA >4 ng/ml to predict PCa was calculated. Receiver operating characteristic curves were used to identify optimal cutoffs in HIV+ men for total PSA. RESULTS: 61 HIV+ men were included with a median 6 (IQR 2-9) years follow-up. Levels of tPSA increased by 13.7% per year (95% CI 10.3, 17.3) in cases, but was stable in controls (-0.4%; 95% CI -2.5, 1.7). Elevated PSA was associated with higher odds of PCa at first (OR for twofold higher 4.7; 95% CI 1.7, 12.9; P<0.01) and last sample (8.1; 95% CI 1.1, 58.9; P=0.04). A similar relationship was seen between fPSA and PCa. Testosterone and SHBG level were not associated with PCa. tPSA level >4 ng/ml had 99% specificity and 38% sensitivity. The optimal PSA cutoff was 1.5 ng/ml overall (specificity =84%, sensitivity =81%). CONCLUSIONS: PSA was highly predictive of PCa in HIV+ men; however, the commonly used PSA>4 ng/ml to indicate high PCa risk was not sensitive in our population and use of the lower cutoff of PSA>1.5 ng/ml warrants consideration.

16 Article Intimate relationships in young adults with perinatally acquired HIV: a qualitative study of strategies used to manage HIV disclosure. 2016

Greenhalgh, Clare / Evangeli, Michael / Frize, Graham / Foster, Caroline / Fidler, Sarah. ·a Department of Clinical Psychology, Royal Holloway , University of London , Surrey , UK. · b The 900 Clinic , Imperial College Healthcare NHS Trust, St. Mary's Hospital , London , UK. ·AIDS Care · Pubmed #26444656.

ABSTRACT: An increasing number of children born with perinatally acquired HIV (PAH) are surviving into late adolescence and early adulthood. At this developmental stage, forming and sustaining intimate relationships is important. Young adults with PAH face both normative challenges and additional, HIV-related, relationship stressors. One key issue is the decision about whether and how to share their HIV status with others. Being able to disclose one's HIV status to sexual partners may reduce the risk of onward HIV transmission but is associated with the fear of rejection. There has been little research on how young people with PAH manage such disclosure-related stressors in intimate relationships. This study examined how disclosure challenges are managed by young adults with PAH in the UK within their intimate relationships. Seven participants (five females and two males) currently or previously in an intimate relationship, aged 18-23 years, were recruited from a UK hospital clinic. The majority of participants were of sub-Saharan African origins. They took part in in-depth interviews, with data analysed according to the principles of interpretative phenomenological analysis. Four themes were elicited: (1) decisions about starting, continuing or resuming relationships shaped by disclosure, (2) disclosing early to avoid the pain of future rejection, (3) using condoms to avoid disclosure and (4) testing likely partner reactions to disclosure. The study revealed the significant extent to which HIV disclosure affected the experience of relationships in this population. Interventions to support adolescents and young adults with PAH to disclose to their partners should be developed alongside guidance for professionals. Future research should include older samples of adults with PAH and studies in sub-Saharan African settings.

17 Article The Impact of HCV Infection Duration on HIV Disease Progression and Response to cART amongst HIV Seroconverters in the UK. 2015

Inshaw, Jamie / Leen, Clifford / Fisher, Martin / Gilson, Richard / Hawkins, David / Collins, Simon / Fox, Julie / McLean, Ken / Fidler, Sarah / Phillips, Andrew / Lattimore, Sam / Babiker, Abdel / Porter, Kholoud / Anonymous110838. ·MRC Clinical Trials Unit at University College London, London, United Kingdom. · Western General Hospital, Edinburgh, United Kingdom. · Brighton and Sussex University NHS Trust, Brighton, United Kingdom. · Department of Infection and Population Health, University College London, London, United Kingdom. · Chelsea and Westminster Hospital, London, United Kingdom. · HIV i-Base, London, United Kingdom. · Guy's and St. Thomas NHS Trust at Kings College, London, United Kingdom. · Charing Cross Hospital, London, United Kingdom. · Imperial College NHS Trust, London, United Kingdom. · Public Health England, London, United Kingdom. ·PLoS One · Pubmed #26225723.

ABSTRACT: INTRODUCTION: The effect of HCV infection on HIV disease progression remains unclear; the effect of HCV infection duration on HIV disease progression is unknown. METHODS: We used data from a cohort of HIV seroconverters to investigate the effect of HCV infection duration on time from HIV seroconversion to CD4 <350 cells/mm3, AIDS or death, censoring at the earlier of cART initiation or last clinic visit, adjusting for confounders and splitting data into follow up periods from HIV seroconversion (<2, 2-4 and >4 years). We additionally compared CD4 cell decline following HCV infection to that of mono-infected individuals with similar HIV infection duration by fitting a random effects model. In a separate analysis, we used linear mixed models to we examine the effect of HCV infection and its duration on CD4 increase over 48 weeks following cART. RESULTS: Of 1655 individuals, 97 (5.9%) were HCV co-infected. HCV<1 year was associated with a higher risk of endpoint in each follow-up period from HIV seroconversion (HR [95% CI] 2.58 [1.51, 4.41], p = 0.001; 3.80 [1.20, 12.03], p = 0.023; 2.03 [0.88, 4.71], p = 0.098 for <2, 2-4 and >4 years respectively), compared to mono-infected individuals. However, we found no evidence of an association for those with HCV>2 years (all p>0.89). Individuals experienced a somewhat greater decrease in CD4 count following HCV infection lasting 13 months, relative to individuals with HIV alone, (estimate = -3.33, 95% CI [-7.29, 0.63] cells/mm3 per month, p = 0.099). Of 1502 initiating cART, 106 (7.1%) were HCV co-infected, with no evidence of HCV duration at cART being associated with immunological response (p = 0.45). CONCLUSIONS: The impact of HCV co-infection on HIV disease progression appears to be restricted to the first year after HCV infection.

18 Article Estimating the cost-effectiveness of pre-exposure prophylaxis to reduce HIV-1 and HSV-2 incidence in HIV-serodiscordant couples in South Africa. 2015

Jewell, Britta L / Cremin, Ide / Pickles, Michael / Celum, Connie / Baeten, Jared M / Delany-Moretlwe, Sinead / Hallett, Timothy B. ·Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom. · Departments of Global Health, Medicine and Epidemiology, University of Washington, Seattle, Washington, United States of America. · Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa. ·PLoS One · Pubmed #25616135.

ABSTRACT: OBJECTIVE: To estimate the cost-effectiveness of daily oral tenofovir-based PrEP, with a protective effect against HSV-2 as well as HIV-1, among HIV-1 serodiscordant couples in South Africa. METHODS: We incorporated HSV-2 acquisition, transmission, and interaction with HIV-1 into a microsimulation model of heterosexual HIV-1 serodiscordant couples in South Africa, with use of PrEP for the HIV-1 uninfected partner prior to ART initiation for the HIV-1 1infected partner, and for one year thereafter. RESULTS: We estimate the cost per disability-adjusted life-year (DALY) averted for two scenarios, one in which PrEP has no effect on reducing HSV-2 acquisition, and one in which there is a 33% reduction. After a twenty-year intervention, the cost per DALY averted is estimated to be $10,383 and $9,757, respectively--a 6% reduction, given the additional benefit of reduced HSV-2 acquisition. If all couples are discordant for both HIV-1 and HSV-2, the cost per DALY averted falls to $1,445, which shows that the impact is limited by HSV-2 concordance in couples. CONCLUSION: After a 20-year PrEP intervention, the cost per DALY averted with a reduction in HSV-2 is estimated to be modestly lower than without any effect, providing an increase of health benefits in addition to HIV-1 prevention at no extra cost. The small degree of the effect is in part due to a high prevalence of HSV-2 infection in HIV-1 serodiscordant couples in South Africa.

19 Article The impact of HIV on children's education in eastern Zimbabwe. 2014

Pufall, Erica L / Nyamukapa, Constance / Eaton, Jeffrey W / Campbell, Catherine / Skovdal, Morten / Munyati, Shungu / Robertson, Laura / Gregson, Simon. ·a Department of Infectious Disease Epidemiology , Imperial College London , London , UK. ·AIDS Care · Pubmed #24625293.

ABSTRACT: Little is known about how HIV impacts directly and indirectly on receiving, or particularly succeeding in, education in sub-Saharan Africa. To address this gap, we used multivariable logistic regression to determine the correlation between education outcomes in youth (aged 15-24) (being in the correct grade-for-age, primary school completion and having at least five "O" level passes) and being HIV-positive; having an HIV-positive parent; being a young carer; or being a maternal, paternal or double orphan, in five rounds (1998-2011) of a general population survey from eastern Zimbabwe. The fifth survey round (2009-2011) included data on children aged 6-17, which were analysed for the impacts of the above risk factors on regular attendance in primary and secondary schools and being in the correct grade-for-age. For data pooled over all rounds, being HIV-positive had no association with primary school completion, "O" level passes, or being in the correct grade-for-age in adolescents aged 16-17 years. Additionally, HIV status had no significant association with any education outcomes in children aged 6-17 surveyed in 2009-2011. In 2009-2011, being a young carer was associated with lower attendance in secondary school (69% vs. 85%, AOR: 0.44; p=0.02), whilst being a maternal (75% vs. 83%, AOR: 0.67; p<0.01), paternal (76% vs. 83%, AOR: 0.67; p=0.02) or double (75% vs. 83%, AOR: 0.68; p=0.02) orphan was associated with decreased odds of being in the correct grade-for-age. All forms of orphanhood also significantly decreased the odds of primary school completion in youths surveyed from 1998 to 2011 (all p<0.01). We found no evidence that HIV status affects education but further evidence that orphans do experience worse education outcomes than other children. Combination approaches that provide incentives for children to attend school and equip schools with tools to support vulnerable children may be most effective in improving education outcomes and should be developed and evaluated.

20 Article Sexual and reproductive health in a UK cohort of young adults perinatally infected with HIV. 2013

Croucher, Adam P / Jose, Sophie / McDonald, Susan / Foster, Caroline / Fidler, Sarah. ·Jefferiss Wing, St Mary’s Hospital, Imperial College Healthcare NHS Trust, London, UK. a.croucher@imperial.ac.uk ·Sex Transm Infect · Pubmed #23434788.

ABSTRACT: OBJECTIVES: To assess sexual health and behaviour outcomes of young adults with perinatally acquired HIV-1 (PaHIV), and audit sexual health interventions against published standards of care. METHODS: Retrospective case note audit of 16-25-year-olds with PaHIV attending a dedicated transition clinic from January 2005 to 2011. RESULTS: Fifty-two young adults, 31 women, median age 20 years. 41 were sexually active; median age of coitarche 16 years. Median number of lifetime partners was 3.5, and five reported non-consensual sex. All had a sexually transmitted infection (STI) screen; 6 were diagnosed with an STI, genital warts (human papilloma virus) most frequently. The median interval from coitarche to first STI screen was 2 years. The pregnancy incidence was 103 per 1000 person years. 18/25 (72%) sexually active women had a cervical smear, four had colposcopy. All patients had hepatitis B virus (HBV) serology. 47 had not been vaccinated against HBV prior to transition. 23 completed HBV vaccination of which 11 had surface antibody >100 IU/ml at 1 year. CONCLUSIONS: The majority of our cohort was sexually active while still under the care of paediatric health services. Cervical screening and hepatitis B vaccination rates fell short of audit standards. Vaccination for hepatitis B should be considered prior to transfer of care to adult HIV services.

21 Article The new role of antiretrovirals in combination HIV prevention: a mathematical modelling analysis. 2013

Cremin, Ide / Alsallaq, Ramzi / Dybul, Mark / Piot, Peter / Garnett, Geoffrey / Hallett, Timothy B. ·Department of Infectious Disease Epidemiology, Imperial College London, UK. ide.cremin05@imperial.ac.uk ·AIDS · Pubmed #23296196.

ABSTRACT: BACKGROUND AND OBJECTIVES: Antiretroviral drugs can reduce HIV acquisition among uninfected individuals (as pre-exposure prophylaxis: PrEP) and reduce onward transmission among infected individuals (as antiretroviral treatment: ART). We estimate the potential impact and cost-effectiveness of antiretroviral-based HIV prevention strategies. DESIGN AND METHODS: We developed and analysed a mathematical model of a hyperendemic setting with relatively low levels of condom use. We estimated the prevention impact and cost of various PrEP interventions, assuming a fixed amount of spending on PrEP; investigated the optimal role of PrEP and earlier ART in terms of epidemiological impact and cost; and systematically explored the impact of earlier ART and PrEP, in combination with medical male circumcision services; on HIV transmission. RESULTS: A PrEP intervention is unlikely to generate a large reduction in HIV incidence, unless the cost is substantially reduced. In terms of infections averted and quality adjusted life years gained, at a population-level maximal cost-effectiveness is achieved by providing ART to more infected individuals earlier rather than providing PrEP to uninfected individuals. However, early ART alone cannot reduce HIV incidence to very low levels and PrEP can be used cost-effectively in addition to earlier ART to reduce incidence further. If implemented in combination and at ambitious coverage levels, medical male circumcision, earlier ART and PrEP could produce dramatic declines in HIV incidence, but not stop transmission completely. CONCLUSION: A combination prevention approach based on proven-efficacy interventions provides the best opportunity for achieving the much hoped for prevention advance and curbing the spread of HIV.

22 Article Characterization of a novel population of low-density granulocytes associated with disease severity in HIV-1 infection. 2012

Cloke, Thomas / Munder, Markus / Taylor, Graham / Müller, Ingrid / Kropf, Pascale. ·Department of Medicine, Section of Immunology, Faculty of Medicine, Imperial College London, London, United Kingdom. ·PLoS One · Pubmed #23152825.

ABSTRACT: The mechanisms resulting in progressive immune dysfunction during the chronic phase of HIV infection are not fully understood. We have previously shown that arginase, an enzyme with potent immunosuppressive properties, is increased in HIV seropositive (HIV+) patients with low CD4(+) T cell counts. Here we show that the cells expressing arginase in peripheral blood mononuclear cells of HIV+ patients are low-density granulocytes (LDGs) and that whereas these cells have a similar morphology to normal-density granulocyte, they are phenotypically different. Importantly, our results reveal that increased frequencies of LDGs correlate with disease severity in HIV+ patients.

23 Article HIV epidemic appraisals for assisting in the design of effective prevention programmes: shifting the paradigm back to basics. 2012

Mishra, Sharmistha / Sgaier, Sema K / Thompson, Laura H / Moses, Stephen / Ramesh, B M / Alary, Michel / Wilson, David / Blanchard, James F. ·Department of Infectious Diseases Epidemiology, Imperial College, London, United Kingdom. ·PLoS One · Pubmed #22396756.

ABSTRACT: BACKGROUND: To design HIV prevention programmes, it is critical to understand the temporal and geographic aspects of the local epidemic and to address the key behaviours that drive HIV transmission. Two methods have been developed to appraise HIV epidemics and guide prevention strategies. The numerical proxy method classifies epidemics based on current HIV prevalence thresholds. The Modes of Transmission (MOT) model estimates the distribution of incidence over one year among risk-groups. Both methods focus on the current state of an epidemic and provide short-term metrics which may not capture the epidemiologic drivers. Through a detailed analysis of country and sub-national data, we explore the limitations of the two traditional methods and propose an alternative approach. METHODS AND FINDINGS: We compared outputs of the traditional methods in five countries for which results were published, and applied the numeric and MOT model to India and six districts within India. We discovered three limitations of the current methods for epidemic appraisal: (1) their results failed to identify the key behaviours that drive the epidemic; (2) they were difficult to apply to local epidemics with heterogeneity across district-level administrative units; and (3) the MOT model was highly sensitive to input parameters, many of which required extraction from non-regional sources. We developed an alternative decision-tree framework for HIV epidemic appraisals, based on a qualitative understanding of epidemiologic drivers, and demonstrated its applicability in India. The alternative framework offered a logical algorithm to characterize epidemics; it required minimal but key data. CONCLUSIONS: Traditional appraisals that utilize the distribution of prevalent and incident HIV infections in the short-term could misguide prevention priorities and potentially impede efforts to halt the trajectory of the HIV epidemic. An approach that characterizes local transmission dynamics provides a potentially more effective tool with which policy makers can design intervention programmes.

24 Article HIV-associated gastric natural killer/T-cell lymphoma. 2012

Manley, K / Dunning, J / Nelson, M / Bower, M. ·Faculty of Medicine, Imperial College London, UK. ·Int J STD AIDS · Pubmed #22362696.

ABSTRACT: Natural killer (NK)/T-cell lymphoma is a rare form of non-Hodgkin's lymphoma that is seen with increased frequency in HIV infection and in transplant recipients. This case report describes an unusual case of extranodal NK/T-cell lymphoma in a patient with advanced HIV disease in which gastric involvement was a significant feature.

25 Article HIV testing uptake and acceptability in an inner city polyclinic. 2012

Ashby, J / Braithewaite, B / Walsh, J / Gnani, S / Fidler, S / Cooke, G. ·St Mary's Hospital, Imperial College NHS Healthcare Trust, London, UK. Jane.ashby@berkshire.nhs.uk ·AIDS Care · Pubmed #22272938.

ABSTRACT: Up to 33% of HIV-infected adults in the UK remain undiagnosed and efforts to increase HIV testing are underway. HIV testing was conducted amongst individuals presenting to a polyclinic at a central London hospital using a point of care test. Demographic and HIV risk data was collected along with a patient feedback questionnaire exploring acceptability of the HIV testing experience. Seventy-one out of 93 (76%) individuals accepted HIV testing. Of those accepting HIV testing, 53/71 (75%) had never previously tested for HIV despite, 45/53 (85%) of these being registered with a GP. Twenty-seven out of 71 (38%) of individuals testing had at least one risk factor associated with HIV acquisition, and of these 17/27 (63%) had never previously tested for HIV infection. There were no new HIV positive diagnoses during the period of testing. Respondents indicated a high level of satisfaction with the service and more than 85% found the service to be helpful, educational and convenient. This small proof of concept pilot showed uptake of HIV testing in this setting to be high and acceptable to patients.