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HIV Seropositivity: HELP
Articles by Kholoud Porter
Based on 23 articles published since 2008

Between 2008 and 2019, Kholoud Porter wrote the following 23 articles about HIV Seropositivity.
+ Citations + Abstracts
1 Clinical Trial Symptomatic illness and low CD4 cell count at HIV seroconversion as markers of severe primary HIV infection. 2013

Lodi, Sara / Fisher, Martin / Phillips, Andrew / De Luca, Andrea / Ghosn, Jade / Malyuta, Ruslan / Zangerle, Robert / Moreno, Santiago / Vanhems, Philippe / Boufassa, Faroudy / Guiguet, Marguerite / Porter, Kholoud / Anonymous300776. ·Instituto de Salud Carlos III, Madrid, Spain. ·PLoS One · Pubmed #24244330.

ABSTRACT: BACKGROUND: The risk/benefit of initiating ART in primary HIV infection (PHI) is unclear. The benefits are more likely to outweigh the risks in patients with severe PHI. An accepted definition of severe PHI is, however, lacking. METHODS: CASCADE patients with HIV test interval <6 months were classified as severe and non-severe PHI based on whether the following traits were recorded in the first 6 months following seroconversion: severe specific pre-defined symptoms, central nervous system-implicated illness, and ≥1, ≥2 CD4<350 (and <500) cells/mm(3). For each definition, we used Kaplan-Meier curves and Cox survival models to compare time to AIDS/death, censoring at the earlier of last clinic visit or 1/1/1997, when combination antiretroviral therapy (cART) became available. RESULTS: Among 1108 included patients mostly males (85%) infected through sex between men (71%), 366 were diagnosed with AIDS/died. The risk of AIDS/death was significantly higher for individuals with severe symptoms, those with ≥1 CD4<350 cells/mm(3) or ≥2 CD4 <500 cells/mm(3) in the first 6 months [aHR (95% confidence interval) 2.1 (1.4,3.2), 2.0 (1.5,2.7), and 2.3, (1.5-3.5) respectively]. Median [interquantile range] survival for patients with ≥2, ≥1 and no CD4<350 cells/mm(3) within 6 months of seroconversion was 3.9 [2.7,6.5], 5.4 [4.5,8.4] and 8.1 [4.3,10.3] years, respectively. The diagnosis of CNS-implicated symptoms was rare and did not appear to be prognostic. CONCLUSION: One CD4 count <350 or two <500 cells/mm(3) within 6 months of seroconversion and/or severe illness in PHI may be useful early indicators of individuals at high risk of disease progression.

2 Article CD4 T cell decline following HIV seroconversion in individuals with and without CXCR4-tropic virus. 2017

Ghosn, Jade / Bayan, Tatiana / Meixenberger, Karolin / Tran, Laurent / Frange, Pierre / d'Arminio Monforte, Antonella / Zangerle, Robert / de Mendoza, Carmen / Krastinova, Evguenia / Porter, Kholoud / Meyer, Laurence / Chaix, Marie-Laure / Anonymous4530925. ·Université Paris Descartes, Sorbonne Paris Cité, Paris, France. · Inserm UMR-S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Université Pierre et Marie Curie, Paris, France. · Inserm, CESP Centre for Research in Epidemiology and Population Health, U1018, HIV Epidemiology, Le Kremlin-Bicêtre, F-94276, France. · Univ Paris-Sud, UMRS 1018, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, F-94276, France. · Robert Koch Institute, HIV and other Retroviruses, Berlin, Germany. · AP-HP, Hopital Bicêtre, Epidemiology and Public Health Service, Le Kremlin Bicêtre, F-94276, France. · AP-HP, Laboratoire de Microbiologie Clinique, Hôpital Universitaire Necker-Enfants Malades, Paris, France. · Infectious Diseases, University of Milan, San Paolo Hospital, Milano, Italy and Health Sciences, University of Milan, San Paolo Hospital, Milano, Italy. · Medical University Innsbruck, Innsbruck, Austria. · Research Institute and University Hospital Puerta de Hierro, Majahonda, Madrid, Spain. · Medical Research Council Clinical Trials Unit, University College London, London, UK. · INSERM U941, Université Paris Diderot, Paris, France. · APHP, Laboratoire de Virologie, Hôpital Saint Louis, Paris, France. ·J Antimicrob Chemother · Pubmed #29091208.

ABSTRACT: Background: The natural clinical and immunological courses following HIV seroconversion with CXCR4-tropic or dual-mixed (X4/DM) viruses are controversial. We compared spontaneous immunological outcome in patients harbouring an X4/DM virus at the time of seroconversion with those harbouring a CCR5-tropic (R5) virus. Methods: Data were included from patients participating in CASCADE, a large cohort collaboration of HIV seroconverters, with ≥2 years of follow-up since seroconversion. The HIV envelope gene was sequenced from frozen plasma samples collected at enrolment, and HIV tropism was determined using Geno2Pheno (false-positive rate 10%). The spontaneous CD4 T cell evolution was compared by modelling CD4 kinetics using linear mixed-effects models with random intercept and random slope. Results: A total of 1387 patients were eligible. Median time between seroconversion and enrolment was 1 month (range 0-3). At enrolment, 202 of 1387 (15%) harboured an X4/DM-tropic virus. CD4 decrease slopes were not significantly different according to HIV-1 tropism during the first 30 months after seroconversion. No marked change in these results was found after adjusting for age, year of seroconversion and baseline HIV viral load. Time to antiretroviral treatment initiation was not statistically different between patients harbouring an R5 (20.76 months) and those harbouring an X4/DM-tropic virus (22.86 months, logrank test P = 0.32). Conclusions: In this large cohort collaboration, 15% of the patients harboured an X4/DM virus close to HIV seroconversion. Patients harbouring X4/DM-tropic viruses close to seroconversion did not have an increased risk of disease progression, estimated by the decline in CD4 T cell count or time to combined ART initiation.

3 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.

4 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.

5 Article The effect of short-course antiretroviral therapy initiated in primary HIV-1 infection on interleukin-6 and D-dimer levels. 2015

Hamlyn, Elizabeth / Stöhr, Wolfgang / Cooper, David A / Fisher, Martin / Tambussi, Giuseppe / Schechter, Mauro / Miro, Jose M / Vanobberghen, Fiona / Babiker, Abdel / Weber, Jonathan / Mcclure, Myra / Porter, Kholoud / Fidler, Sarah / Anonymous6910826. ·aImperial College London bKings College Hospital NHS Foundation Trust cMedical Research Council Clinical Trials Unit at University College London, London, UK dKirby Institute, University of New South Wales, Sydney, Australia eBrighton and Sussex University Hospitals, Brighton, UK fOspedale San Raffaele, Milan, Italy gProjeto Praça Onze, Hospital Escola São Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil hHospital Clinic-Institut d'investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain iLondon School of Hygiene & Tropical Medicine, London, UK. *Kholoud Porter and Sarah Fidler contributed equally to the writing of this manuscript. ·AIDS · Pubmed #25870986.

ABSTRACT: OBJECTIVE: Interruption of antiretroviral therapy (ART) in chronic HIV disease is associated with increased mortality, predicted by elevations in interleukin-6 (IL-6) and D-dimer. The effect of ART interruption in primary HIV-1 infection on these biomarkers is unknown. METHODS: Plasma samples from 200 HIV seroconverters enrolled in the Short Pulse Anti-Retroviral Therapy At HIV Seroconversion trial of deferred ART (standard of care) - 12 or 48 week ART (ART12 or ART48, respectively) - were analysed for IL-6 and D-dimer at weeks 0, 12, 16, 48, 52, 60 and 108 after randomization. Changes in log10 levels from weeks 0 to 12 were analysed using linear regression, as were changes from baseline to 4 weeks after stopping ART. Areas under the biomarker-time curves (AUC) to week 108 were adjusted for baseline values, and compared across all arms. RESULTS: Median (inter-quartile range) baseline IL-6 and D-dimer were 1.45 (0.88, 2.41) pg/ml and 0.34 (0.20, 0.50) mg/l, respectively. At week 12, D-dimer levels were significantly lower among treated compared to untreated individuals (P < 0.001), whereas IL-6 levels were similar (P = 0.23). Within 4 weeks from stopping ART, IL-6 and D-dimer levels rose by 22 and 18%, reaching pre-ART levels. Over 108-week follow-up, there was no difference between arms in IL-6 AUC (P = 0.53), but D-dimer AUC was significantly lower for ART12 and ART48 compared to standard of care (overall P = 0.008). CONCLUSION: Stopping ART in primary HIV-1 infection leads to inflammatory biomarker rebound to pre-treatment levels. However, over 108-week follow-up, we found no evidence that biomarker levels were higher for those interrupting ART, compared to those remaining ART-naïve, and D-dimer levels were significantly lower.

6 Article An evaluation of HIV elite controller definitions within a large seroconverter cohort collaboration. 2014

Olson, Ashley D / Meyer, Laurence / Prins, Maria / Thiebaut, Rodolphe / Gurdasani, Deepti / Guiguet, Marguerite / Chaix, Marie-Laure / Amornkul, Pauli / Babiker, Abdel / Sandhu, Manjinder S / Porter, Kholoud / Anonymous5300783. ·Medical Research Council Clinical Trials Unit at University College London, London, United Kingdom. · Institut National de la Santé et de la Recherche Médicale U1018, Université Paris-Sud, le Kremlin-Bicêtre, France. · Amsterdam Public Health Service, Amsterdam, Netherlands. · Institut National de la Santé et de la Recherche Médicale U897, Université Bordeaux Segalen, Bordeaux, France. · Wellcome Trust Sanger Institute, Hinxton, United Kingdom ; University of Cambridge, Cambridge, United Kingdom. · Institut National de la Santé et de la Recherche Médicale U943, Paris, France ; Université Pierre et Marie Curie S943, Paris, France. · Université Paris Descartes, EA 3620, Hôpital Necker-Enfants Malades, Paris, France. · International AIDS Vaccine Initiative, San Francisco, California, United States of America. ·PLoS One · Pubmed #24489776.

ABSTRACT: BACKGROUND: Understanding the mechanisms underlying viral control is highly relevant to vaccine studies and elite control (EC) of HIV infection. Although numerous definitions of EC exist, it is not clear which, if any, best identify this rare phenotype. METHODS: We assessed a number of EC definitions used in the literature using CASCADE data of 25,692 HIV seroconverters. We estimated proportions maintaining EC of total ART-naïve follow-up time, and disease progression, comparing to non-EC. We also examined HIV-RNA and CD4 values and CD4 slope during EC and beyond (while ART naïve). RESULTS: Most definitions classify ∼ 1% as ECs with median HIV-RNA 43-903 copies/ml and median CD4>500 cells/mm(3). Beyond EC status, median HIV-RNA levels remained low, although often detectable, and CD4 values high but with strong evidence of decline for all definitions. Median % ART-naïve time as EC was ≥ 92% although overlap between definitions was low. EC definitions with consecutive HIV-RNA measurements <75 copies/ml with follow-up ≥ six months, or with 90% of measurements <400 copies/ml over ≥ 10 year follow-up preformed best overall. Individuals thus defined were less likely to progress to endpoint (hazard ratios ranged from 12.5-19.0 for non-ECs compared to ECs). CONCLUSIONS: ECs are rare, less likely to progress to clinical disease, but may eventually lose control. We suggest definitions requiring individuals to have consecutive undetectable HIV-RNA measurements for ≥ six months or otherwise with >90% of measurements <400 copies/ml over ≥ 10 years be used to define this phenotype.

7 Article Interleukin-6 and D-dimer levels at seroconversion as predictors of HIV-1 disease progression. 2014

Hamlyn, Elizabeth / Fidler, Sarah / Stöhr, Wolfgang / Cooper, David A / Tambussi, Giuseppe / Schechter, Mauro / Miro, Jose M / Mcclure, Myra / Weber, Jonathan / Babiker, Abdel / Porter, Kholoud / Anonymous4990777. ·aImperial College London bKings College Hospital NHS Foundation Trust cMedical Research Council Clinical Trials Unit at University College London, London, UK dKirby Institute, University of New South Wales, Sydney, New South Wales, Australia eOspedale San Raffaele, Milan, Italy fProjeto Praça Onze, Hospital Escola São Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil gHospital Clinic-Institut d'investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain. ·AIDS · Pubmed #24300544.

ABSTRACT: OBJECTIVE: Inflammation and coagulation biomarkers interleukin (IL)-6 and D-dimer are predictive of all-cause mortality in chronic HIV-1 infection; however, their predictive value in individuals with recent infection has not been described. METHODS: SPARTAC was a randomized controlled trial comparing three strategies of intervention in primary HIV-1 infection [no therapy, 12-week or 48-week antiretroviral therapy (ART)]. Plasma IL-6 and D-dimer were measured in 200 participants from sites in Australia, Brazil, UK and Italy. We evaluated age, sex/HIV risk group, time since HIV-1 seroconversion, baseline HIV-RNA, CD4 cell count and BMI as possible predictors of IL-6 and D-dimer levels at seroconversion using multivariable linear regression. For participants remaining ART-naive, we evaluated whether baseline IL-6 and D-dimer levels independently predicted time to reaching CD4 cell count less than 350 cells/μl or initiating ART using multivariable Cox proportional hazards models. RESULTS: Median (interquartile range, IQR) baseline IL-6 and D-dimer levels were 1.45 (0.88-2.41) pg/ml and 0.34 (0.20-0.50) μg/l, respectively. Higher levels were associated with older age (P=0.008 and 0.004, respectively). Higher D-dimer levels were associated with higher HIV-RNA (P<0.001). For the 73 participants not initiating ART (median follow-up 225 weeks), of whom 48 reached the primary endpoint, higher baseline IL-6, but not D-dimer, was independently associated with a shorter time to primary endpoint [hazard ratio=1.38 per additional pg/ml, 95% confidence interval (CI) 1.09-1.75; P=0.007]. Other baseline predictors were older age (P=0.030), higher RNA (P=0.033) and lower CD4 cell count (P<0.001). CONCLUSION: IL-6 levels at time of HIV-1 seroconversion independently predict HIV-1 disease progression in patients with primary HIV-1 infection.

8 Article Role of HIV infection duration and CD4 cell level at initiation of combination anti-retroviral therapy on risk of failure. 2013

Lodi, Sara / Phillips, Andrew / Fidler, Sarah / Hawkins, David / Gilson, Richard / McLean, Ken / Fisher, Martin / Post, Frank / Johnson, Anne M / Walker-Nthenda, Louise / Dunn, David / Porter, Kholoud / Anonymous1720771. ·Medical Research Council, University College London, London, United Kingdom ; Instituto de Salud Carlos III, Madrid, Spain. ·PLoS One · Pubmed #24086588.

ABSTRACT: BACKGROUND: The development of HIV drug resistance and subsequent virological failure are often cited as potential disadvantages of early cART initiation. However, their long-term probability is not known, and neither is the role of duration of infection at the time of initiation. METHODS: Patients enrolled in the UK Register of HIV seroconverters were followed-up from cART initiation to last HIV-RNA measurement. Through survival analysis we examined predictors of virologic failure (2HIV-RNA ≥400 c/l while on cART) including CD4 count and HIV duration at initiation. We also estimated the cumulative probabilities of failure and drug resistance (from the available HIV nucleotide sequences) for early initiators (cART within 12 months of seroconversion). RESULTS: Of 1075 starting cART at a median (IQR) CD4 count 272 (190,370) cells/mm(3) and HIV duration 3 (1,6) years, virological failure occurred in 163 (15%). Higher CD4 count at initiation, but not HIV infection duration at cART initiation, was independently associated with lower risk of failure (p=0.033 and 0.592 respectively). Among 230 patients initiating cART early, 97 (42%) discontinued it after a median of 7 months; cumulative probabilities of resistance and failure by 8 years were 7% (95% CI 4,11) and 19% (13,25), respectively. CONCLUSION: Although the rate of discontinuation of early cART in our cohort was high, the long-term rate of virological failure was low. Our data do not support early cART initiation being associated with increased risk of failure and drug resistance.

9 Article Natural history of HIV-control since seroconversion. 2013

Madec, Yoann / Boufassa, Faroudy / Porter, Kholoud / Prins, Maria / Sabin, Caroline / d'Arminio Monforte, Antonella / Amornkul, Pauli / Bartmeyer, Barbara / Sannes, Mette / Venet, Alain / Lambotte, Olivier / Meyer, Laurence / Anonymous5220765. ·aInstitut Pasteur, Emerging Diseases Epidemiology Unit, Paris bINSERM U1018, Centre de Recherche en Epidémiologie et Santé des Populations, Le Kremlin-Bicêtre cFaculté de Médecine Paris Sud, Université Paris Sud, Paris dDepartment of Public Health, AP-HP, Bicêtre Hospital, Le Kremlin-Bicêtre, France eMedical Research Council, Clinical Trials Unit, London, UK fCluster Infectious Diseases, Department of Research, Center for Infection and Immunity Amsterdam (CINIMA), Public Health Service, Amsterdam, The Netherlands gResearch Department of Infection and Population Health, UCL Medical School, London, UK hSan Paolo Hospital, Milan, Italy iInternational AIDS Vaccine Initiative, San Francisco, USA jRobert Koch Institut, Berlin, Germany kUlleval Hospital, Oslo, Norway lINSERM U1012, Le Kremlin-Bicêtre mDepartment of Internal Medicine, AP-HP, Bicêtre Hospital, Le Kremlin-Bicêtre nUniversité Paris-Sud, Paris, France. ·AIDS · Pubmed #23912979.

ABSTRACT: OBJECTIVES: HIV-controllers spontaneously maintain HIV viremia at an undetectable level. We aimed to describe the delay to control from seroconversion, the duration of control, and risk factors for losing control. METHODS: HIV-controllers were identified from a pooled dataset of 24 seroconverter cohorts from Europe, Australia, and Canada (CASCADE). HIV-controllers had at least five consecutive viral loads less than 400/500 copies/ml, while antiretroviral therapy naive, for at least 5 years after seroconversion. End of control was defined as two consecutive viral loads above 2000 copies/ml. Duration of control was described using Kaplan-Meier estimates; factors associated with duration of control were identified using a Cox model. CD4⁺ cell count evolution during control was described using a mixed model. RESULTS: Of 9896 eligible seroconverters, we identified 140 (1.4%) HIV-controllers, the largest database of HIV-controllers followed from seroconversion. For 64 with viral load measured within 24 months from seroconversion, median delay to control was 16.7 (interquartile range: 7.8-37.9) months. Probability of maintaining control 20 years after seroconversion was 0.74 [95% confidence interval (CI): 0.64-0.85]. Occurrence of blips followed by return to undetectability did not increase the risk of loss of control [hazard ratio: 0.81 (95% CI: 0.10-6.70)]. However, CD4⁺ cell loss during control was significantly accelerated in individuals with blips. CONCLUSION: In most individuals, control occurred rapidly after seroconversion; however, more than 3 years were required to achieve control in 25% of HIV-controllers. Control may be sustained even when CD4⁺ cell levels are below 500 cells/μl, opening important new perspectives to understand the physiopathology underlying control.

10 Article Effect of HCV infection on cause-specific mortality after HIV seroconversion, before and after 1997. 2013

van der Helm, Jannie / Geskus, Ronald / Sabin, Caroline / Meyer, Laurence / Del Amo, Julia / Chêne, Geneviève / Dorrucci, Maria / Muga, Roberto / Porter, Kholoud / Prins, Maria / Anonymous6920745. ·Public Health Service Amsterdam, Amsterdam, the Netherlands. jvdhelm@ggd.amsterdam.nl ·Gastroenterology · Pubmed #23266560.

ABSTRACT: BACKGROUND & AIMS: Individuals with human immunodeficiency virus (HIV) infection frequently also are infected with hepatitis C virus (HCV) (co-infection), but little is known about its effects on the progression of HIV-associated disease. We aimed to determine the effects of co-infection on mortality from HIV and/or acquired immune deficiency syndrome (AIDS), and hepatitis or liver disease, adjusting for the duration of HIV infection. METHODS: We analyzed data from the 16 cohorts of the Concerted Action on Seroconversion to AIDS and Death in Europe (CASCADE) collaboration, which included information on HCV infection and cause of death. A competing-risks proportional subdistribution hazards model was used to evaluate the effect of HCV infection on the following causes of death: HIV- and/or AIDS-related, hepatitis- or liver-related, natural, and non-natural. RESULTS: Of 9164 individuals with HIV infection and a known date of seroconversion, 2015 (22.0%) also were infected with HCV. Of 718 deaths, 395 (55.0%) were caused by HIV infection and/or AIDS, and 39 (5.4%) were caused by hepatitis or liver-related disease. Among individuals infected with only HIV or with co-infection, the mortality from HIV infection and/or AIDS-related causes and hepatitis or liver disease decreased significantly after 1997, when combination antiretroviral therapy became widely available. However, after 1997, HIV and/or AIDS-related mortality was higher among co-infected individuals than those with only HIV infection in each risk group: injection drug use (adjusted hazard ratio [aHR], 2.43; 95% confidence interval [CI], 1.14-5.20), sex between men and women or hemophilia (aHR, 3.43; 95% CI, 1.70-6.93), and sex between men (aHR, 3.11; 95% CI, 1.49-6.48). Compared with individuals infected with only HIV, co-infected individuals had a higher risk of death from hepatitis or liver disease. CONCLUSIONS: Based on analysis of data from the CASCADE collaboration, since 1997, when combination antiretroviral therapy became widely available, individuals co-infected with HIV and HCV have had a higher risk of death from HIV and/or AIDS, and from hepatitis or liver disease, than patients infected with only HIV. It is necessary to evaluate the effects of HCV therapy on HIV progression.

11 Article Impact of HIV-1 subtype on CD4 count at HIV seroconversion, rate of decline, and viral load set point in European seroconverter cohorts. 2013

Touloumi, Giota / Pantazis, Nikos / Pillay, Deenan / Paraskevis, Dimitrios / Chaix, Marie-Laure / Bucher, Heiner C / Kücherer, Claudia / Zangerle, Robert / Kran, Anne-Marte Bakken / Porter, Kholoud / Anonymous3090744. ·Department of Hygiene, Epidemiology and Medical Statistics, Athens University Medical School, Greece. gtouloum@med.uoa.gr ·Clin Infect Dis · Pubmed #23223594.

ABSTRACT: BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) subtype may influence disease progression. We compared CD4 lymphocyte cell count levels at seroconversion, decline rates and viral load set point in individuals infected with different HIV-1 subtypes. METHODS: We used data from the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) collaboration, restricted to those infected since 1996, aged ≥15 years, and applied mixed effects models for CD4 cell count decline and median regression for viral load set point (mean level 6-24 months from seroconversion). RESULTS: The analysis included 3364 seroconverters with known HIV-1 subtypes. Compared with subtype B, CD4 at seroconversion was significantly higher for subtype CRF01 and lower for subtype C. Subsequent CD4 decline was significantly slower for subtypes A and CRF02 and marginally slower for subtype C compared with B. Mean CD4 loss at 2 years of seroconversion for white men exposed through sex between men, aged 30-39 years, having seroconverted since 2006, enrolled within 6 months of seroconversion, and without acute infection was 88, 142, 100, 130, 103, and 167 cells/µL for subtypes A, B, C, CRF01_AE, CRF02_AG, and G, respectively. In adjusted analysis, median viral load set point and time to clinical AIDS/death did not differ significantly by subtype, although all subtypes, except C, tended to have lower levels compared with B. CONCLUSIONS: HIV-1 subtype significantly influences seroconversion CD4 cell levels and decline rates but not viral load set point. These findings may be helpful to HIV-positive individuals and their attending physicians in understanding disease progression.

12 Article Risk of tuberculosis following HIV seroconversion in high-income countries. 2013

Lodi, Sara / del Amo, Julia / d'Arminio Monforte, Antonella / Abgrall, Sophie / Sabin, Caroline / Morrison, Charles / Furrer, Hansjakob / Muga, Roberto / Porter, Kholoud / Girardi, Enrico / Anonymous1440741. ·Clinical Trials Unit, Medical Research Council, London, UK. slodi@isciii.es ·Thorax · Pubmed #23117980.

ABSTRACT: BACKGROUND: Few data exist on tuberculosis (TB) incidence according to time from HIV seroconversion in high-income countries and whether rates following initiation of a combination of antiretroviral treatments (cARTs) differ from those soon after seroconversion. METHODS: Data on individuals with well estimated dates of HIV seroconversion were used to analyse post-seroconversion TB rates, ending at the earliest of 1 January 1997, death or last clinic visit. TB rates were also estimated following cART initiation, ending at the earliest of death or last clinic visit. Poisson models were used to examine the effect of current and past level of immunosuppression on TB risk after cART initiation. RESULTS: Of 19 815 individuals at risk during 1982-1996, TB incidence increased from 5.89/1000 person-years (PY) (95% CI 3.77 to 8.76) in the first year after seroconversion to 10.56 (4.83 to 20.04, p=0.01) at 10 years. Among 11 178 TB-free individuals initiating cART, the TB rate in the first year after cART initiation was 4.23/1000 PY (3.07 to 5.71) and dropped thereafter, remaining constant from year 2 onwards averaging at 1.64/1000 PY (1.29 to 2.05). Current CD4 count was inversely associated with TB rates, while nadir CD4 count was not associated with TB rates after adjustment for current CD4 count, HIV-RNA at cART initiation. CONCLUSIONS: TB risk increases with duration of HIV infection in the absence of cART. Following cART initiation, TB incidence rates were lower than levels immediately following seroconversion. Implementation of current recommendations to prevent TB in early HIV infection could be beneficial.

13 Article Time to virological failure, treatment change and interruption for individuals treated within 12 months of HIV seroconversion and in chronic infection. 2012

Zugna, Daniela / Geskus, Ronald B / De Stavola, Bianca / Rosinska, Magdalena / Bartmeyer, Barbara / Boufassa, Faroudy / Chaix, Marie-Laure / Babiker, Abdel / Porter, Kholoud / Anonymous4680734. ·Cancer Epidemiology Unit, CeRMS and CPO-Piemonte, University of Turin, Turin, Italy. ·Antivir Ther · Pubmed #22910338.

ABSTRACT: BACKGROUND: Estimates of treatment failure, change and interruption are lacking for individuals treated in early HIV infection. METHODS: Using CASCADE data, we compared the effect of treatment in early infection (within 12 months of seroconversion) with that seen in chronic infection on risk of virological failure, change and interruption. Failure was defined as two subsequent measures of HIV RNA>1,000 copies/ml following suppression (<500 copies/ml), or >500 copies/ml 6 months following initiation. Treatment change and interruption were defined as modification or interruption lasting >1 week. In multivariable competing risks proportional subdistribution hazards models, we adjusted for combination antiretroviral therapy (cART) class, sex, risk group, age, CD4(+) T-cell count, HIV RNA and calendar period at treatment initiation. RESULTS: Of 1,627 individuals initiating cART early (median 1.8 months from seroconversion), 159, 395 and 692 failed, changed and interrupted therapy, respectively. For 2,710 individuals initiating cART in chronic infection (median 35.9 months from seroconversion), the corresponding values were 266, 569 and 597. Adjusted hazard ratios (HRs; 95% CIs) for treatment failure and change were similar between the two treatment groups (0.93 [0.72, 1.20] and 1.06 [0.91, 1.24], respectively). There was an increasing trend in rates of interruption over calendar time for those treated early, and a decreasing trend for those starting treatment in chronic infection. Consequently, compared with chronic infection, treatment interruption was similar for early starters in the early cART period, but the relative hazard increased over calendar time (1.54 [1.33, 1.79] in 2000). CONCLUSIONS: Individuals initiating treatment in early HIV infection are more likely to interrupt treatment than those initiating later. However, rates of failure and treatment change were similar between the two groups.

14 Article Immunovirologic control 24 months after interruption of antiretroviral therapy initiated close to HIV seroconversion. 2012

Lodi, Sara / Meyer, Laurence / Kelleher, Anthony D / Rosinska, Magdalena / Ghosn, Jade / Sannes, Mette / Porter, Kholoud. ·Instituto de Salud Carlos III, Centro Nacional de Epidemiologia, Madrid, Spain. ·Arch Intern Med · Pubmed #22826124.

ABSTRACT: BACKGROUND: There is interest in whether a short course of combination antiretroviral therapy (cART) at the time of human immunodeficiency virus (HIV) seroconversion could induce long-term immunologic control after its interruption. We aimed to determine the time of virologic rebound after interruption of treatment initiated close to HIV seroconversion and to identify potential cases of posttreatment controllers (PTCs) in the CASCADE (Concerted Action on Seroconversion to AIDS and Death in Europe) Collaboration. METHODS: Prospective cohort study nested within the CASCADE database of routinely collected data about patients with HIV with well-estimated date of HIV seroconversion from Europe, Canada, and Australia in the post-cART era. Participants were individuals who interrupted successful cART initiated within 3 months of HIV seroconversion. The main outcome was loss of PTC status, defined as the earlier date of virologic rebound (first of 2 consecutive measurements showing HIV RNA levels >50 copies/mL) or reinitiation of any ART after cART interruption. RESULTS: Median time to loss of PTC status in 259 eligible individuals was 1.7 months. Eleven patients did not experience virologic rebound by 24 months after treatment interruption. CONCLUSION: Most patients experience virologic rebound soon after cART interruption; however, although PTCs are rare, the results of this study confirm their existence.

15 Article Differences in HIV natural history among African and non-African seroconverters in Europe and seroconverters in sub-Saharan Africa. 2012

Pantazis, Nikos / Morrison, Charles / Amornkul, Pauli N / Lewden, Charlotte / Salata, Robert A / Minga, Albert / Chipato, Tsungai / Jaffe, Harold / Lakhi, Shabir / Karita, Etienne / Porter, Kholoud / Meyer, Laurence / Touloumi, Giota / Anonymous4620720. ·Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. npantaz@med.uoa.gr ·PLoS One · Pubmed #22412867.

ABSTRACT: INTRODUCTION: It is unknown whether HIV treatment guidelines, based on resource-rich country cohorts, are applicable to African populations. METHODS: We estimated CD4 cell loss in ART-naïve, AIDS-free individuals using mixed models allowing for random intercept and slope, and time from seroconversion to clinical AIDS, death and antiretroviral therapy (ART) initiation by survival methods. Using CASCADE data from 20 European and 3 sub-Saharan African (SSA) cohorts of heterosexually-infected individuals, aged ≥15 years, infected ≥2000, we compared estimates between non-African Europeans, Africans in Europe, and Africans in SSA. RESULTS: Of 1,959 (913 non-Africans, 302 Europeans-African origin, 744 SSA), two-thirds were female; median age at seroconversion was 31 years. Individuals in SSA progressed faster to clinical AIDS but not to death or non-TB AIDS. They also initiated ART later than Europeans and at lower CD4 cell counts. In adjusted models, Africans (especially from Europe) had lower CD4 counts at seroconversion and slower CD4 decline than non-African Europeans. Median (95% CI) CD4 count at seroconversion for a 15-29 year old woman was 607 (588-627) (non-African European), 469 (442-497) (European-African origin) and 570 (551-589) (SSA) cells/µL with respective CD4 decline during the first 4 years of 259 (228-289), 155 (110-200), and 199 (174-224) cells/µL (p<0.01). DISCUSSION: Despite differences in CD4 cell count evolution, death and non-TB AIDS rates were similar across study groups. It is therefore prudent to apply current ART guidelines from resource-rich countries to African populations.

16 Article Time from human immunodeficiency virus seroconversion to reaching CD4+ cell count thresholds <200, <350, and <500 Cells/mm³: assessment of need following changes in treatment guidelines. 2011

Lodi, Sara / Phillips, Andrew / Touloumi, Giota / Geskus, Ronald / Meyer, Laurence / Thiébaut, Rodolphe / Pantazis, Nikos / Amo, Julia Del / Johnson, Anne M / Babiker, Abdel / Porter, Kholoud / Anonymous2510705. ·MRC Clinical Trials Unit, University College London, UK. sal@ctu.mrc.ac.uk ·Clin Infect Dis · Pubmed #21921225.

ABSTRACT: BACKGROUND: Recent updates of human immunodeficiency virus (HIV) treatment guidelines have raised the CD4+ cell count thresholds for antiretroviral therapy initiation from 350 to 500 cells/mm(3) in the United States and from 200 to 350 cells/mm³ in mid- and low-income countries. Robust data of time from HIV seroconversion to CD4+ cell counts of 200, 350, and 500 cells/mm³ are lacking but are needed to inform health care planners of the likely impact and cost effectiveness of these and possible future changes in CD4+ cell count initiation threshold. METHODS: Using Concerted Action on Seroconversion to AIDS and Death in Europe data from individuals with well-estimated dates of HIV seroconversion, we fitted mixed models on the square root of CD4+ cell counts measured before combined antiretroviral therapy (cART) initiation. Restricting analyses to adults (age >16 years), we predicted time between seroconversion and CD4+ cell count <200, <350, and <500 cells/mm³ as well as CD4+ cell count distribution and proportions reaching these thresholds at 1, 2, and 5 years after seroconversion. RESULTS: Median (interquartile range [IQR]) follow-up for the 18495 eligible individuals from seroconversion while cART-free was 3.7 years (1.5, 7). Most of the subjects were male (78%), had a median age at seroconversion of 30 years (IQR, 25-37 years), and were infected through sex between men (55%). Estimated median times (95% confidence interval [CI]) from seroconversion to CD4+ cell count <500, <350, and <200 cells/mm(3) were 1.19 (95% CI, 1.12-1.26), 4.19 (95% CI, 4.09-4.28), and 7.93 (95% CI, 7.76-8.09) years, respectively. Almost half of infected individuals would require treatment within 1 year of seroconversion for guidelines recommending its initiation at 500 cells/mm³, compared with 26% and 9% for guidelines recommending initiation at 350 and 200 cells/mm³, respectively. CONCLUSIONS: These data suggest substantial increases in the number of individuals who require treatment and call for early HIV testing.

17 Article The hepatitis C epidemic among HIV-positive MSM: incidence estimates from 1990 to 2007. 2011

van der Helm, Jannie J / Prins, Maria / del Amo, Julia / Bucher, Heiner C / Chêne, Geneviève / Dorrucci, Maria / Gill, John / Hamouda, Osamah / Sannes, Mette / Porter, Kholoud / Geskus, Ronald B / Anonymous2560693. ·Cluster of Infectious Diseases, Public Health Service Amsterdam, Amsterdam, The Netherlands. jvdhelm@ggd.amsterdam.nl ·AIDS · Pubmed #21537114.

ABSTRACT: BACKGROUND: Outbreaks of acute hepatitis C virus (HCV) infection among HIV-infected MSM have been described since 2000. However, phylogenetic analysis suggests that the spread of HCV started around 1996. We estimated the incidence of HCV in HIV-infected MSM with well estimated dates of HIV seroconversion from 1990 to 2007. METHODS: Data from 12 cohorts within the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) Collaboration were used. HCV incidence was estimated using standard incidence methods and methods for interval-censored data. We accounted for the fact that routine HCV data collection in each cohort started in different calendar years. RESULTS: Of 4724 MSM, 3014 had an HCV test result and were included. Of these, 124 (4%) had only positive HCV test results, 2798 (93%) had only negative results and 92 (3%) had both. In 1990, HCV incidence ranged from 0.9 to 2.2 per 1000 person-years, depending on the analysis strategy used. HCV incidence increased up to 1995 when it was estimated to range between 5.5 and 8.1 per 1000 person-years. From 2002 onwards, it increased substantially to values between 16.8 and 30.0 per 1000 person-years in 2005 and between 23.4 and 51.1 per 1000 person-years in 2007. CONCLUSION: Our data support phylodynamic findings that HCV incidence had already increased among HIV-infected MSM from the mid-1990s. However, the main expansion of the HCV epidemic started after 2002. Incidence estimates obtained from cohort studies may help identify changes in the spread of important infections earlier and should guide routine testing policies to minimize further disease burden.

18 Article CD4 decline in seroconverter and seroprevalent individuals in the precombination of antiretroviral therapy era. 2010

Lodi, Sara / Phillips, Andrew / Touloumi, Giota / Pantazis, Nikos / Bucher, Heiner C / Babiker, Abdel / Chêne, Geneviève / Vanhems, Philippe / Porter, Kholoud / Anonymous5590673. ·MRC Clinical Trials Unit, London, UK. sal@ctu.mrc.ac.uk ·AIDS · Pubmed #20885283.

ABSTRACT: BACKGROUND: Studies based on seroconverters have increased our understanding of HIV disease. It is not clear, however, whether their disease progression differs from that of the general HIV population, given their reasons for presenting for testing. METHODS: Using linear mixed models we compared CD4 decline rates for a seroconverter (CASCADE) and seroprevalent group (Concorde trial) with time origin being dates of seroconversion and randomization, respectively. Follow-up was censored at the earlier of last alive date and 1 January 1996. Analyses were adjusted for risk group, age and sex. To explore the role of symptomatic seroconversion we further categorized seroconverters into two groups: with and without an HIV test interval below 30 days as proxy. RESULTS: The 7226 seroconverter and 1746 seroprevalent eligible individuals were mainly men (78 and 85%, respectively) infected through sex between men (52 and 63%) with mean [95% confidence interval (CI)] baseline CD4 cell count of 610 (602, 619) and 492 (479, 505) cells/μl, respectively. There was no evidence that rate of CD4 decline differs between the two groups even after adjusting for potential confounders (P = 0.67). Estimated loss in the year after reaching an arbitrary threshold of 400 cells/μl was 67 (95% CI 65, 69) and 67 (64, 69) cells/μl in the seroconverter and seroprevalent group, respectively. Whereas seroconverters with test interval below 30 days (n = 310) experienced faster decline, there was no difference in rates between other seroconverters and seroprevalent individuals (P = 0.87). CONCLUSIONS: These data suggest that estimates of HIV progression derived from seroconverters are likely to hold more generally for the HIV-infected population.

19 Article Death rates in HIV-positive antiretroviral-naive patients with CD4 count greater than 350 cells per microL in Europe and North America: a pooled cohort observational study. 2010

Anonymous160666 / Lodwick, Rebecca K / Sabin, Caroline A / Porter, Kholoud / Ledergerber, Bruno / van Sighem, Ard / Cozzi-Lepri, Alessandro / Khaykin, Pavel / Mocroft, Amanda / Jacobson, Lisa / De Wit, Stephane / Obel, Niels / Castagna, Antonella / Wasmuth, Jan-Christian / Gill, John / Klein, Marina B / Gange, Stephen / Riera, Melchor / Mussini, Cristina / Gutiérrez, Félix / Touloumi, Giota / Carrieri, Patrizia / Guest, Jodie L / Brockmeyer, Norbert H / Phillips, Andrew N. ·HIV Epidemiology and Biostatistics Group, Research Department of Infection and Population Health, UCL Medical School, Royal Free Campus, London, UK. r.lodwick@ucl.ac.uk ·Lancet · Pubmed #20638118.

ABSTRACT: BACKGROUND: Whether people living with HIV who have not received antiretroviral therapy (ART) and have high CD4 cell counts have higher mortality than the general population is unknown. We aimed to examine this by analysis of pooled data from industrialised countries. METHODS: We merged data on demographics, CD4 cell counts, viral-load measurements, hepatitis C co-infection status, smoking status, date of death, and whether death was AIDS-related or not from 23 European and North American cohorts. We calculated standardised mortality ratios (SMRs) standardised by age, sex, and year, stratifying by risk group. Data were included for patients aged 20-59 years who had at least one CD4 count greater than 350 cells per microL while ART naive. All pre-ART CD4 counts greater than 350 cells per microL from January, 1990, to December, 2004, were included. We investigated mortality for four risk groups--men who have sex with men, heterosexual people, injecting drug users, and those at other or unknown risk. The association between CD4 cell count and death rate was investigated by use of Poisson regression methods. FINDINGS: Data were analysed for 40,830 patients contributing 80,682 person-years of follow-up. Of 419 deaths, 401 were used in the SMR analysis: 100 men who have sex with men (SMR 1.30, 95% CI 1.06-1.58); 68 heterosexual people (2.94, 2.28-3.73); 203 injecting drug users (9.37, 8.13-10.75); and 30 in the other or unknown risk category (4.57, 3.09-6.53). Compared with CD4 counts of 350-499 cells per microL, death rate was lower in patients with counts of 500-699 cells per microL (adjusted rate ratio 0.77, 95% CI 0.61-0.95) and counts of 700 cells per microL (0.66, 0.52-0.85). INTERPRETATION: In HIV-infected ART-naive patients with high CD4 cell counts, death rates were raised compared with the general population. In men who have sex with men this was modest, suggesting that a substantial proportion of the increased risk in other groups is due to confounding by other factors. Even though the increased risk is small, new studies of potential benefits of ART in this group are merited. FUNDING: European Commission, FP6. European AIDS Treatment Network (NEAT). Project number LSHP-CT-2006-037570.

20 Article Kaposi sarcoma incidence and survival among HIV-infected homosexual men after HIV seroconversion. 2010

Lodi, Sara / Guiguet, Marguerite / Costagliola, Dominique / Fisher, Martin / de Luca, Andrea / Porter, Kholoud / Anonymous6340659. ·Medical Research Council, Clinical Trials Unit, 222 Euston Rd, London NW1 2DA, UK. sal@ctu.mrc.ac.uk ·J Natl Cancer Inst · Pubmed #20442214.

ABSTRACT: BACKGROUND: Despite the success of combination antiretroviral therapy (cART) in reducing the incidence of Kaposi sarcoma, HIV-infected individuals who have responded to treatment continue to be diagnosed with Kaposi sarcoma. We examine factors associated with the incidence of Kaposi sarcoma among cART-treated HIV-infected homosexual men and changes in their survival after its diagnosis over calendar time. METHODS: Data were from HIV-infected homosexual men with well-estimated dates of HIV seroconversion (ie, change in status from being HIV negative to having HIV antibodies detected). Incidence of Kaposi sarcoma was calculated. We used Kaplan-Meier methods to determine survival after Kaposi sarcoma diagnosis in three calendar periods: before 1996, 1996-2000, and 2001-2006. Poisson models were used to examine the effect of risk factors such as current and nadir CD4 cell count (ie, the lowest CD4 cell count ever recorded for a person), duration of infection, and age at diagnosis for Kaposi sarcoma incidence in cART-treated men. All statistical tests were two-sided. RESULTS: Among the 9473 men, 555 were diagnosed with Kaposi sarcoma in the period 1986-2006, of whom 319 died. The percentage surviving 24 months after Kaposi sarcoma diagnosis rose statistically significantly during the study period from 35% (95% confidence interval [CI] = 29% to 42%) before 1996 to 84% (95% CI = 76% to 90%) in 1996-2000 and to 81% (95% CI = 70% to 88%) in 2001-2006 (P < .001). Seventy men were diagnosed with Kaposi sarcoma after starting cART. Current (ie, within 6 months) CD4 cell count was associated with incidence of Kaposi sarcoma among cART-treated men (rate ratios [RRs] = 18.91, 95% CI = 8.50 to 42.09, for CD4 level category <200 cells per cubic millimeter; RR = 3.55, 95% CI = 1.40 to 9.00, for 200-349 cells per cubic millimeter; and RR = 4.11, 95% CI = 1.74 to 9.70, for 350-499 cells per cubic millimeter; all compared with > or = 500 cells per cubic millimeter). After adjustment for current CD4 cell count, HIV infection duration, age, or nadir CD4 cell count was not associated with Kaposi sarcoma incidence. CONCLUSIONS: Among cART-treated HIV-infected homosexual men, current CD4 cell count was the factor most strongly associated with the incidence of Kaposi sarcoma. Survival estimates after Kaposi sarcoma diagnosis have improved over time.

21 Article Gender differences in HIV progression to AIDS and death in industrialized countries: slower disease progression following HIV seroconversion in women. 2008

Jarrin, Inmaculada / Geskus, Ronald / Bhaskaran, Krishnan / Prins, Maria / Perez-Hoyos, Santiago / Muga, Roberto / Hernández-Aguado, Ildefonso / Meyer, Laurence / Porter, Kholoud / del Amo, Julia / Anonymous5160604. ·National Center of Epidemiology, Instituto de Salud Carlos III, Madrid, Spain. ·Am J Epidemiol · Pubmed #18663213.

ABSTRACT: To evaluate sex differences in human immunodeficiency virus (HIV) disease progression before (pre-1997) and after (1997-2006) introduction of highly active antiretroviral therapy, the authors used data from a collaboration of 23 HIV seroconverter cohort studies from Europe, Australia, and Canada restricted to the 6,923 seroconverters infected through injecting drug use and sex between men and women. Within a competing risk framework, they used Cox proportional hazards models allowing for late entry to evaluate sex differences in time from HIV seroconversion to death, to acquired immunodeficiency syndrome (AIDS), and to each first AIDS-defining disease and death without AIDS. While no significant sex differences were found before 1997, from 1997 onward, women had a lower risk of AIDS (adjusted cumulative relative risk (aCRR) = 0.76, 95% confidence interval (CI): 0.63, 0.90) and death (adjusted hazard ratio = 0.68, 95% CI: 0.56, 0.82) than men did. Compared with men, women also had lower risks of AIDS dementia complex (aCRR = 0.23, 95% CI: 0.07, 0.74), tuberculosis (aCRR = 0.60, 95% CI: 0.39, 0.92), Kaposi's sarcoma (aCRR = 0.27, 95% CI: 0.07, 0.99), lymphomas (aCRR = 0.47, 95% CI: 0.23, 0.96), and death without AIDS (aCRR = 0.74, 95% CI: 0.56, 0.98). Sex differences in HIV disease progression have become larger and statistically significant in the era of highly active antiretroviral therapy, supporting a stronger impact of health interventions among women.

22 Article Changes in the risk of death after HIV seroconversion compared with mortality in the general population. 2008

Bhaskaran, Krishnan / Hamouda, Osamah / Sannes, Mette / Boufassa, Faroudy / Johnson, Anne M / Lambert, Paul C / Porter, Kholoud / Anonymous3920602. ·MRC Clinical Trials Unit, 222 Euston Rd, London NW1 2DA, United Kingdom. kp@ctu.mrc.ac.uk ·JAMA · Pubmed #18594040.

ABSTRACT: CONTEXT: Mortality among human immunodeficiency virus (HIV)-infected individuals has decreased dramatically in countries with good access to treatment and may now be close to mortality in the general uninfected population. OBJECTIVE: To evaluate changes in the mortality gap between HIV-infected individuals and the general uninfected population. DESIGN, SETTING, AND POPULATION: Mortality following HIV seroconversion in a large multinational collaboration of HIV seroconverter cohorts (CASCADE) was compared with expected mortality, calculated by applying general population death rates matched on demographic factors. A Poisson-based model adjusted for duration of infection was constructed to assess changes over calendar time in the excess mortality among HIV-infected individuals. Data pooled in September 2007 were analyzed in March 2008, covering years at risk 1981-2006. MAIN OUTCOME MEASURE: Excess mortality among HIV-infected individuals compared with that of the general uninfected population. RESULTS: Of 16,534 individuals with median duration of follow-up of 6.3 years (range, 1 day to 23.8 years), 2571 died, compared with 235 deaths expected in an equivalent general population cohort. The excess mortality rate (per 1000 person-years) decreased from 40.8 (95% confidence interval [CI], 38.5-43.0; 1275.9 excess deaths in 31,302 person-years) before the introduction of highly active antiretroviral therapy (pre-1996) to 6.1 (95% CI, 4.8-7.4; 89.6 excess deaths in 14,703 person-years) in 2004-2006 (adjusted excess hazard ratio, 0.05 [95% CI, 0.03-0.09] for 2004-2006 vs pre-1996). By 2004-2006, no excess mortality was observed in the first 5 years following HIV seroconversion among those infected sexually, though a cumulative excess probability of death remained over the longer term (4.8% [95% CI, 2.5%-8.6%] in the first 10 years among those aged 15-24 years). CONCLUSIONS: Mortality rates for HIV-infected persons have become much closer to general mortality rates since the introduction of highly active antiretroviral therapy. In industrialized countries, persons infected sexually with HIV now appear to experience mortality rates similar to those of the general population in the first 5 years following infection, though a mortality excess remains as duration of HIV infection lengthens.

23 Minor Immunovirologic control 24 months after interruption of antiretroviral therapy initiated close to HIV seroconversion--reply. 2013

Porter, Kholoud / Lodi, Sara / Meyer, Laurence. · ·JAMA Intern Med · Pubmed #23529555.

ABSTRACT: -- No abstract --