Genital inflammation undermines the effectiveness of tenofovir gel in preventing HIV acquisition in women.
Lyle R. McKinnon,Lyle R. McKinnon,Lyle R. McKinnon,Lenine J. P. Liebenberg,Lenine J. P. Liebenberg,Nonhlanhla Yende-Zuma,Derseree Archary,Derseree Archary,Sinaye Ngcapu,Sinaye Ngcapu,Aida Sivro,Aida Sivro,Aida Sivro,Nico J. D. Nagelkerke,Jose Gerardo Garcia Lerma,Angela D. M. Kashuba,Lindi Masson,Lindi Masson,Leila E. Mansoor,Quarraisha Abdool Karim,Quarraisha Abdool Karim,Salim S. Abdool Karim,Salim S. Abdool Karim,Jo-Ann S. Passmore,Jo-Ann S. Passmore,Jo-Ann S. Passmore +25 more
TLDR
A post hoc prospective analysis of results from the CAPRISA 004 trial for 1% tenofovir gel, one of the first trials to demonstrate protection against HIV infection, found that reducing genital inflammation in women may augment HIV prevention efforts.Abstract:
Several clinical trials have demonstrated that antiretroviral (ARV) drugs taken as pre-exposure prophylaxis (PrEP) can prevent HIV infection, with the magnitude of protection ranging from -49 to 86% (refs. ). Although these divergent outcomes are thought to be due primarily to differences in product adherence, biological factors likely contribute. Despite selective recruitment of higher-risk participants for prevention trials, HIV risk is heterogeneous even within higher-risk groups. To determine whether this heterogeneity could influence patient outcomes following PrEP, we undertook a post hoc prospective analysis of results from the CAPRISA 004 trial for 1% tenofovir gel (n = 774 patients), one of the first trials to demonstrate protection against HIV infection. Concentrations of nine proinflammatory cytokines were measured in cervicovaginal lavages at >2,000 visits, and a graduated cytokine score was used to define genital inflammation. In women without genital inflammation, tenofovir was 57% protective against HIV (95% confidence interval (CI): 7-80%) but was 3% protective (95% CI: -104-54%) if genital inflammation was present. Among women who highly adhered to the gel, tenofovir protection was 75% (95% CI: 25-92%) in women without inflammation compared to -10% (95% CI: -184-57%) in women with inflammation. Immunological predictors of HIV risk may modify the effectiveness of tools for HIV prevention; reducing genital inflammation in women may augment HIV prevention efforts.read more
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Human Dendritic Cell Subsets, Ontogeny, and Impact on HIV Infection.
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Teodora Wi,Francis Ndowa,Cecilia Ferreyra,Cassandra Kelly-Cirino,Melanie M Taylor,Igor Toskin,James Kiarie,Nancy Santesso,Magnus Unemo +8 more
TL;DR: The diagnostic accuracy of syndromic case management and existing point-of-care tests, including those in the pipeline, to diagnose STIs in resource‐constrained settings are reviewed.
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Myron S. Cohen,Jane S Chen +1 more
TL;DR: This review is designed to investigate the complex relationship between HIV and classical STIs and the potential for HIV acquisition in people at risk for HIV.
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The genital tract and rectal microbiomes: their role in HIV susceptibility and prevention in women.
Salim S. Abdool Karim,Salim S. Abdool Karim,Cheryl Baxter,Jo-Ann S. Passmore,Jo-Ann S. Passmore,Jo-Ann S. Passmore,Lyle R. McKinnon,Lyle R. McKinnon,Lyle R. McKinnon,Brent L. Williams +9 more
TL;DR: The vaginal microbiome is described and its alterations, its influence on HIV acquisition as well as the efficacy of HIV prevention technologies, the role of the rectal microbiome in HIV acquisition, advances in technologies to study the microbiome and some future research directions are examined.
Journal ArticleDOI
Mechanisms of sexually transmitted infection‐induced inflammation in women: implications for HIV risk
Ruth S. Mwatelah,Lyle R. McKinnon,Lyle R. McKinnon,Cheryl Baxter,Quarraisha Abdool Karim,Quarraisha Abdool Karim,Salim S. Abdool Karim,Salim S. Abdool Karim +7 more
TL;DR: It is described how STIs interact with the immune and non‐immune cells, both within and below the cervicovaginal mucosal barrier, to cause inflammation, which in turn has been associated with increased HIV acquisition risk.
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