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. ; The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under EuroCoord grant agreement no. 260694. Sara Lodi is holder of a Juan de la Cierva Fellowship (grant number JCI 2010-08151). There are no current external funding sources for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ; Sí
IntroductionTransmission of Hepatitis C virus (HCV) among HIV‐positive men who have sex with men (MSM) in the United Kingdom is ongoing. We explore associations between self‐reported sexual behaviours and drug use with cumulative HCV prevalence, as well as new HCV diagnosis.MethodsASTRA is a cross‐sectional questionnaire study including 2,248 HIV‐diagnosed MSM under care in the United Kingdom during 2011–2012. Socio‐demographic, lifestyle, HIV‐related and sexual behaviour data were collected during the study. One thousand seven hundred and fifty two (≥70%) of the MSM who consented to linkage of ASTRA and clinical information (prior to and post questionnaire) were included. Cumulative prevalence of HCV was defined as any positive anti‐HCV or HCV‐RNA test result at any point prior to questionnaire completion. We excluded 536 participants with clinical records only after questionnaire completion. Among the remaining 1,216 MSM, we describe associations of self‐reported sexual behaviours and recreational drug use in the three months prior to ASTRA with cumulative HCV prevalence, using modified Poisson regression with robust error variances. New HCV was defined as any positive anti‐HCV or HCV‐RNA after questionnaire completion. We excluded 591 MSM who reported ever having a HCV diagnosis at questionnaire, any positive HCV result prior to questionnaire or did not have any HCV tests after the questionnaire. Among the remaining 1,195 MSM, we describe occurrence of new HCV diagnosis during follow‐up according to self‐reported sexual behaviours and recreational drug use three months prior to questionnaire (Fisher's exact test).ResultsCumulative HCV prevalence among MSM prior to ASTRA was 13.3% (95% CI 11.5–15.4). Clinic‐ and age‐adjusted prevalence ratios (95% CI) for cumulative HCV prevalence were 4.6 (3.1–6.7) for methamphetamine, 6.5 (3.5–12.1) for injection drugs, 2.3 (1.6–3.4) for gamma hydroxybutyrate (GHB), 1.6 (1.3–2.0) for nitrites, 1.7 (1.5–2.0) for all condom‐less sex (CLS), 2.1 (1.7–2.5) for CLS‐HIV‐seroconcordant, 1.3 (0.9–1.9) for CLS‐HIV‐serodiscordant, 2.0 (1.6–2.5) for group sex, 1.5 (1.2–1.9) for more than 10 new sexual partners in the past year. Among 1,195 MSM with 2.2 years [IQR 1.5–2.4] median follow‐up, there were 7 new HCV cases during 2,033 person‐years at risk. Incidence was 3.5 per 1,000 person‐years (95% CI 1.6–7.2). New HCV was recorded in 1.3% MSM who used methamphetamine versus 0.5% MSM who did not (p=0.385); 3.7% MSM who injected recreational drugs versus 0.5% MSM who did not (p=0.148); 2.9% MSM who used GHB versus 0.4% MSM who did not (p=0.003); 1.5% MSM who used nitrites versus 0.2% MSM who did not (p=0.019); 1.1% MSM having CLS versus 0.3% MSM who did not (p=0.084); 1.7% MSM having CLS‐HIV‐serodiscordant versus 0.4% MSM who did not (p=0.069); 0.9% MSM who had CLS‐HIV‐seroconcordant versus 0.5% MSM who did not (p=0.318); 0.8% MSM who had group sex versus 0.5% MSM who did not (p=0.463); and 1.6% MSM with =10 new sexual partners in the previous year versus 0.2% MSM with no or up to 9 new partners (p=0.015).ConclusionsSelf‐reported recent use of recreational and injection drugs, condom‐less sex and multiple new sexual partners are associated with pre‐existing HCV infection and, with the exception of injection drugs, appear to be predictive of new HCV co‐infection among HIV‐diagnosed MSM.
Background. Previous genetic association studies of human immunodeficiency virus-1 (HIV-1) progression have focused on common human genetic variation ascertained through genome-wide genotyping. Methods. We sought to systematically assess the full spectrum of functional variation in protein coding gene regions on HIV-1 progression through exome sequencing of 1327 individuals. Genetic variants were tested individually and in aggregate across genes and gene sets for an influence on HIV-1 viral load. Results. Multiple single variants within the major histocompatibility complex (MHC) region were observed to be strongly associated with HIV-1 outcome, consistent with the known impact of classical HLA alleles. However, no single variant or gene located outside of the MHC region was significantly associated with HIV progression. Set-based association testing focusing on genes identified as being essential for HIV replication in genome-wide small interfering RNA (siRNA) and clustered regularly interspaced short palindromic repeats (CRISPR) studies did not reveal any novel associations. Conclusions. These results suggest that exonic variants with large effect sizes are unlikely to have a major contribution to host control of HIV infection. ; This study has been financed in part within the framework of the Swiss HIV Cohort Study (www.shcs.ch) project #651 and supported by the Swiss National Science Foundation (www.snf.ch) grant #148522 (J.F.). The International HIV Controllers Study was made possible through a generous donation from the Mark and Lisa Schwartz Foundation and a subsequent award from the Collaboration for AIDS Vaccine Discovery of the Bill and Melinda Gates Foundation (www.cavd.org). This work was also supported in part by the Harvard University Center for AIDS Research (cfar.globalhealth.harvard.edu) grant P-30-AI060354; University of California San Francisco (UCSF) Center for AIDS Research (cfar.ucsf.edu) grant P-30 AI27763; UCSF Clinical and Translational Science Institute (https://ctsi.ucsf.edu) grant UL1 RR024131; Center for AIDS Research Network of Integrated Clinical Systems (http://cfar.globalhealth.harvard.edu) grant R24 AI067039; and the National Institutes for Health (www.nih.gov) grants AI28568 and AI030914 (B.D.W.). The AIDS Clinical Trials Group was supported by NIH grants AI069513, AI34835, AI069432, AI069423, AI069477, AI069501, AI069474, AI069428, AI69467, AI069415, Al32782, AI27661, AI25859, AI28568, AI30914, AI069495, AI069471, AI069532, AI069452, AI069450, AI069556, AI069484, AI069472, AI34853, AI069465, AI069511, AI38844, AI069424, AI069434, AI46370, AI68634, AI069502, AI069419, AI068636, RR024975, AI077505, AI110527, and TR000445 (D.W.H.). For the CASCADE Consortium, the research leading to these results has received funding from the European Union Seventh Programme (FP7/2007–2013) under EuroCoord (www.eurocoord.net) grant agreement no. 260694 (K.P.) and the Spanish Network of HIV/AIDS grant nos. RD06/006, RD12/0017/0018 and RD16CIII/0002/0006 (J.DA.). A portion of the data in this manuscript were collected by the Multicenter AIDS Cohort Study (MACS). MACS (Principal Investigators): Johns Hopkins University Bloomberg School of Public Health (Joseph Margolick, Todd Brown), U01-AI35042; Northwestern University (Steven Wolinsky), U01-AI35039; University of California, Los Angeles (Roger Detels, Oto Martinez-Maza, Otto Yang), U01-AI35040; University of Pittsburgh (Charles Rinaldo, Lawrence A. Kingsley, Jeremy J. Martinson), U01-AI35041; the Center for Analysis and Management of MACS, Johns Hopkins University Bloomberg School of Public Health (Lisa Jacobson, Gypsyamber D'Souza), UM1-AI35043. The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute of Mental Health (NIMH). Targeted supplemental funding for specific projects was also provided by the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute on Deafness and Communication Disorders (NIDCD). MACS data collection is also supported by UL1-TR001079 (JHU ICTR) from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH), Johns Hopkins ICTR, or NCATS. The MACS website is located at http://aidscohortstudy.org/ ; Sí
