Oral abstract (OA01): Location, Location, Location: Mucosal Mediators of Risk

This session addressed the importance of understanding the role of the mucosal female genital tract (FGT) in the risk of HIV acquisition and the efficacy of PrEP.

Mucosal inflammation for example can increase the risk of HIV infection by recruiting and activating immune target cells in the FGT. Fowke and colleagues presented data showing that when daily low dose acetylsalicylic acid (ASA) is administered to HIV-negative low risk women, there was a 35% and 28% reduction, respectively, in CCR5+ CD4+ T cells and Th17 cells in the FGT. They concluded that daily use of ASA could be a novel approach that, when combined other methods of prevention, might reduce the risk of HIV infection.

Hormonal contraception (HC) is among strategies used to prevent unwanted pregnancies. However, HC may affect HIV-1 risk through changes in FGT microbiota. Balle et al. examined the impact of three HC methods on the adolescent FGT microbiota and related mucosal cytokine levels in a randomized, crossover trial. Adolescent girls (n=131), aged 15 to 19 were enrolled and randomized into three study arms: 1. injectable norethisterone enanthate (NET-EN), 2. combined oral contraceptives (COCs) or 3. combined contraceptive vaginal ring (CCVR) for 16 weeks. Participants were then switched to a second HC for four months. Use of COCs was found to be associated with lower microbial diversity and decreased abundance of bacterial vaginosis (BV)-associated bacteria in the vagina correlating with lower inflammation and potentially a lower HIV risk.

Pre-exposure prophylaxis (PrEP) in women has been found to have highly variable efficacy which has recently been associated with dysbiotic vaginal microbiota. Cheu et al. investigated the mechanism(s) underlying how vaginal bacteria might alter PrEP drug levels through bacteria-mediated metabolism. By co-culturing Jurkat cells (HIV targets) with PrEP drugs (tenofovir [TFV], tenofovir alafenamide [TAF], and dapirivine [DPV]) the investigators found that vaginal dysbiosis can metabolize PrEP drugs including TFV and DPV. This highlights the role that the microbiome can play in drug uptake to target sites and systemic availability and how this may affect virus transmission and treatment for prevention. Thus, understanding the vaginal microbiome and prevention of BV are critical for improving HIV prevention strategies.