Background: Women in Africa, especially young women, have very high human immunodeficiency virus (HIV) incidence rates that cannot be fully explained by behavioral risks. We investigated whether genital inflammation influenced HIV acquisition in this group.
Methods: Twelve selected cytokines, including 9 inflammatory cytokines and chemokines (interleukin [IL]-1α, IL-1β, IL-6, tumor necrosis factor-α, IL-8, interferon-γ inducible protein-10 [IP-10], monocyte chemoattractant protein-1, macrophage inflammatory protein [MIP]-1α, MIP-1β), hematopoietic IL-7, and granulocyte macrophage colony-stimulating factor, and regulatory IL-10 were measured prior to HIV infection in cervicovaginal lavages from 58 HIV seroconverters and 58 matched uninfected controls and in plasma from a subset of 107 of these women from the Centre for the AIDS Programme of Research in South Africa 004 tenofovir gel trial.
Results: HIV seroconversion was associated with raised genital inflammatory cytokines (including chemokines MIP-1α, MIP-1β, and IP-10). The risk of HIV acquisition was significantly higher in women with evidence of genital inflammation, defined by at least 5 of 9 inflammatory cytokines being raised (odds ratio, 3.2; 95% confidence interval, 1.3-7.9; P = .014). Genital cytokine concentrations were persistently raised (for about 1 year before infection), with no readily identifiable cause despite extensive investigation of several potential factors, including sexually transmitted infections and systemic cytokines.
Conclusions: Elevated genital concentrations of HIV target cell-recruiting chemokines and a genital inflammatory profile contributes to the high risk of HIV acquisition in these African women.
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http://dx.doi.org/10.1093/cid/civ298 | DOI Listing |
J Acquir Immune Defic Syndr
December 2024
Division of Infectious Diseases and Global Public Health, University of California San Diego, San Diego, CA.
Background: Little is known about the efficacy of preexposure prophylaxis (PrEP) or what biologic factors may influence HIV transmission in transgender men (TGM). In this study, we sought to explore the effect of testosterone on the vaginal microbiome, cervicovaginal fluid (CVF) tenofovir concentrations, and levels of CVF inflammatory markers in TGM on PrEP.
Methods: Cervicovaginal fluid was collected from 13 TGM (7 using testosterone) and 32 cisgender women (CGW) on PrEP.
PLoS One
January 2025
Maple Health Group, LLC, New York, United States of America.
The US faces substantial demographic and geographic disparities in both HIV burden and access to pre-exposure prophylaxis (PrEP), an effective strategy to prevent HIV acquisition. Long-acting cabotegravir (CAB) is a novel, injectable PrEP option which demonstrated superior reduction in risk of HIV acquisition compared to daily-oral PrEP in the HPTN083 trial. We modelled the impact of increased PrEP initiations and the introduction of long-acting CAB on HIV incidence among men who have sex with men (MSM) in Atlanta, Georgia, a population with a high burden of HIV.
View Article and Find Full Text PDFPurpose Of Review: Women are underrepresented in HIV infection and prevention research despite making up half of people living with HIV. The female genital tract (FGT) serves as a primary site of HIV acquisition, but gaps in knowledge remain regarding protective innate immune mechanisms. Innate lymphoid cells are tissue-resident cells involved in mucosal barrier maintenance and protection, and innate lymphoid cells (ILCs) are altered during chronic HIV infection.
View Article and Find Full Text PDFBMC Infect Dis
January 2025
Department of Global Health, University of Washington, Seattle, USA.
Background: Increased risk of HIV acquisition during pregnancy and lactation among women is evident, necessitating their inclusion in the evaluation of new HIV prevention interventions. Pregnant and postpartum women specifically face challenges with oral PrEP associated with stigma, and the burden of using other tablets. Long-acting products may address challenges related to oral PrEP, however, there is limited data on product-specific preferences and acceptability among pregnant and lactating women.
View Article and Find Full Text PDFSci Transl Med
January 2025
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Elicitation of HIV broadly neutralizing antibodies (bnAbs) by vaccination first requires the activation of diverse precursors, followed by successive boosts that guide these responses to enhanced breadth through the acquisition of somatic mutations. Because HIV bnAbs contain mutations in their B cell receptors (BCRs) that are rarely generated during conventional B cell maturation, HIV vaccine immunogens must robustly engage and expand B cells with BCRs that contain these improbable mutations. Here, we engineered an immunogen that activates diverse precursors of an HIV V3-glycan bnAb and promotes their acquisition of a functionally critical improbable mutation.
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