Impact of the Genital Microbiota and Microbiome-Focused Clinical Interventions on Mucosal Immunology and HIV Susceptibility Rupert Kaul Departments of Immunology & Medicine, University of Toronto, Canada
Background: Genital immunology is a key determinant of HIV susceptibility, and is strongly modulated by the vaginal microbiota. The vaginal microbiome of African, Caribbean and other Black (ACB) women tends to be characterized by increased diversity and a predominance of Lactobacillus iners. Methods: We conducted a clinical trial to assess the impact of standard oral metronidazole treatment on genital immune parameters of HIV risk in Kenyan women with BV. The primary endpoint was ex vivo cervical CD4+ T cell HIV susceptibility after one month; secondary endpoints included genital cytokine/chemokine levels, cervical immune cell populations, and the composition of the cervico-vaginal microbiota. Results: BV resolved (Nugent score ≤3) at one month in approximately half the participants. Cervical CD4+ T cell HIV entry was moderately reduced, regardless of clinical outcome, and the resolution of BV and reduced abundances of BV-associated gram-negative taxa correlated with reduced genital IL-1α/β. Interestingly, BV resolution and the concomitant increase in Lactobacillus iners substantially increased several genital chemokines that were previously associated with HIV acquisition, including IP-10, MIP-3α, and MIG. In an independent cohort of ACB women, most of who were BV-free, these vaginal chemokines were again closely linked with L. iners abundance,though not other Lactobacillus spp. Conclusion:BV treatment reduced genital CD4+ T cell HIV susceptibility and IL-1 levels, but increased genital chemokines that might enhance HIV susceptibility; the latter effect was related to the restoration of an Lactobacillus iners-dominated microbiota. Further studies may be needed before treatment of asymptomatic BV can be recommended for HIV prevention in ACB communities.
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