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AbstractIntroductionPre‐exposure prophylaxis (PrEP) is highly effective, although PrEP adherence and persistence has been variable during real world implementation. Little is known about missed opportunities to enhance PrEP adherence among individuals who later HIV seroconverted after using PrEP. The goal of this analysis was to identify all HIV infections among individuals who had accessed PrEP in an integrated health system in San Francisco, and to identify potentially intervenable factors that could have prevented HIV infection through in‐depth interviews with people who HIV seroconverted after using PrEP.MethodsWe identified individuals who initiated PrEP in an integrated safety‐net public health system and performed in‐depth chart review to determine person‐time on and after stopping PrEP over six years. We identified all PrEP seroconversions using the Centers for Disease Control and Prevention's Enhanced HIV/AIDS Reporting System and then calculated HIV incidence while using PrEP and during gaps in use. We then performed in‐depth interviews with those who seroconverted.ResultsOverall, 986 initiated PrEP across the San Francisco Department of Public Health from July 2012 to November 2018. Data were gathered from 895 person‐years on PrEP and 953 after stopping PrEP. The HIV incidence was 7.5‐fold higher after stopping PrEP compared to while on PrEP (95% CI 1 to 336). Of the eight individuals who HIV seroconverted; only one was taking PrEP at the time of seroconversion but was using on‐demand PrEP inconsistently. All eight agreed to qualitative interviews. Major barriers to PrEP persistence included substance use, mental health and housing loss; difficulty accessing PrEP due to cost, insurance, and the cost and time of medical visits; difficulty weighing PrEP's benefit versus self‐perceived risk; and entering a primary partnership. The individual who developed HIV using on‐demand PrEP reported confusion about the dosing regimen and which sexual encounters required accompanying PrEP dosing.ConclusionsHIV incidence during gaps in PrEP use was nearly eight‐fold higher than while on PrEP in this large cohort in San Francisco. Many individuals who stop PrEP remain at risk of HIV, and participants reported that proactive outreach could potentially have prevented HIV infections. Individuals using non‐daily PrEP may require additional education and support in the United States.

AbstractIntroduction: Evidence suggests that, of all affected populations, transgender women (transwomen) may have the heaviest HIV burden worldwide. Little is known about HIV linkage and care outcomes for transwomen. We aimed to estimate population‐level indicators of the HIV cascade of care continuum, and to evaluate factors associated with viral suppression among transwomen in Rio de Janeiro, Brazil.Methods: We conducted a respondent‐driven sampling (RDS) study of transwomen from August 2015 to January 2016 in Rio de Janeiro, Brazil and collected data on linkage and access to care, antiretroviral treatment and performed HIV viral load testing. We derived population‐based estimates of cascade indicators using sampling weights and conducted RDS‐weighted logistic regression analyses to evaluate correlates of viral suppression (viral load ≤50 copies/mL).Results: Of the 345 transwomen included in the study, 89.2% (95% CI 55–100%) had been previously tested for HIV, 77.5% (95% CI 48.7–100%) had been previously diagnosed with HIV, 67.2% (95% CI 39.2–95.2) reported linkage to care, 62.2% (95% CI 35.4–88.9) were currently on ART and 35.4% (95% CI 9.5–61.4%) had an undetectable viral load. The final adjusted RDS‐weighted logistic regression model for viral suppression indicated that those who self‐identified as black (adjusted odds ratio [aOR] 0.06, 95% CI 0.01–0.53, p < 0.01), reported earning ≤U$160/month (aOR 0.11, 95% CI 0.16–0.87, p = 0.04) or reported unstable housing (aOR 0.08, 95% CI 0.01–0.43, p < 0.01) had significantly lower odds of viral suppression.Conclusions: Our cascade indicators for transwomen showed modest ART use and low viral suppression rates. Multi‐level efforts including gender affirming care provision are urgently needed to decrease disparities in HIV clinical outcomes among transwomen and reduce secondary HIV transmission to their partners.

The HIV Research for Prevention (HIVR4P) conference is dedicated to advancing HIV prevention research, responding to a growing consensus that effective and durable prevention will require a combination of approaches as well as unprecedented collaboration among scientists, practitioners, and community workers from different fields and geographic areas. The conference theme in 2018, "From Research to Impact," acknowledged an increasing focus on translation of promising research findings into practical, accessible, and affordable HIV prevention options for those who need them worldwide. HIVR4P 2018 was held in Madrid, Spain, on 21-25 October, with >1,400 participants from 52 countries around the globe, representing all aspects of HIV prevention research and implementation. The program included 137 oral and 610 poster presentations. This article presents a brief summary of highlights from the conference. More detailed information, complete abstracts as well as webcasts and daily Rapporteur summaries may be found on the conference website. ; Supported by Gilead who provided funding. Gilead has had no input into the content of the materials used at this meeting/conference. No other pharmaceutical company has had input into the content of the materials used at this conference. HIVR4P 2018 was made possible in part by 1 R13 AI136762-01 from the National Institute of Allergy and Infectious Diseases (NIAID). The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government. ; Sí

Altres ajuts: This work was funded by grants from the National Institutes of Health (RO1AI46995 to P.G.) and the Wellcome Trust (WT104748MA to P.G.). This project has been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research under contract no. HHSN261200800001E (to M.C.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported in part by the Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research. The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), U01-AI35042 (Johns Hopkins University Bloomberg School of Public Health; Joseph Margolick, rincipal investigator [PI]), U01-AI35039 (Northwestern University; Steven Wolinsky, PI), U01-AI35040 (University of California, Los Angeles; Roger Detels and Oto Martinez, multiple principal investigators [MPI]), U01-AI35041 (University of Pittsburgh; Charles Rinaldo, PI), and UM1-AI35043 (Johns Hopkins University Bloomberg School of Public Health; Lisa Jacobson, PI). The SCOPE cohort was supported by the UCSF/Gladstone Institute of Virology and Immunology CFAR (P30 AI027763) and the CFAR Network of Integrated Systems (R24 AI067039). Additional support was provided by the Delaney AIDS Research Enterprise (DARE; AI096109 and A127966) and the amfAR Institute for HIV Cure Research (amfAR 109301). P.B. is a Jenner Investigator. I.W. and P.P. are funded by MRC Programme grant MR/K012037. ; The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05-restricted CD8 + T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8 + T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are associated with slower disease progression and lower viral loads. The effect of HLA-B*27:02 appeared to be consistently stronger than that of HLA-B*27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02-restricted CD8 + T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol KY9 subdominant and Gag KK10 further subdominant. This selection was driven by structural differences in the F pocket, mediated by a polymorphism between these two HLA alleles at position 81. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all three of these CD8 + T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef VW9-mediated selection pressure. These studies demonstrate that HLA-B*27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05. In combination with the protective Gag KK10 and Pol KY9 CD8 + T-cell responses that dominate HIV-specific CD8 + T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9-specific response is additionally present and immunodominant in HLA-B*27:02-positive subjects, mediated through a polymorphism at residue 81 in the F pocket, that contributes to selection pressure against HIV. IMPORTANCE CD8 + T cells play a central role in successful control of HIV infection and have the potential also to mediate the eradication of viral reservoirs of infection. The principal means by which protective HLA class I molecules, such as HLA-B*27:05 and HLA-B*57:01, slow HIV disease progression is believed to be via the particular HIV-specific CD8 + T cell responses restricted by those alleles. We focus here on HLA-B*27:05, one of the best-characterized protective HLA molecules, and the closely related HLA-B*27:02, which differs by only 3 amino acids and which has not been well studied in relation to control of HIV infection. We show that HLA-B*27:02 is also protective against HIV disease progression, but the CD8 + T-cell immunodominance hierarchy of HLA-B*27:02 differs strikingly from that of HLA-B*27:05. These findings indicate that the immunodominant HLA-B*27:02-restricted Nef response adds to protection mediated by the Gag and Pol specificities that dominate anti-HIV CD8 + T-cell activity in HLA-B*27:05-positive subjects.