Impact of bacterial vaginosis treatment on the genital immune and microbial parameters of HIV susceptibility

Genital immunology is a key determinant of HIV susceptibility. Both factors are modulated by bacterial vaginosis (BV) and to some extent by L. iners, the genital Lactobacillus spp. that predominates in African, Caribbean and other Black (ACB) women. We assessed the impact of 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 by16S rRNA gene amplicon sequencing. BV resolved (Nugent score ≤3) at one month in 20/45 participants, and cervical CD4+ T cell HIV entry was moderately reduced, regardless of treatment outcome. Resolution of BV and reduced abundances of BV-associated gram-negative taxa correlated with reduced genital levels of IL-1a and IL-1b. However, BV resolution and the concomitant increased abundance of L. iners substantially increased several genital chemokines associated with HIV acquisition, including IP-10, MIP-3a, and MIG. In an independent cohort of ACB women, most of whom were BV-free, vaginal chemokines were again closely correlated with the abundance of L. iners, though not with other Lactobacillus spp. In conclusion, BV treatment reduced genital CD4+ T cell HIV susceptibility and IL-1 levels, but increased levels of genital chemokines that enhance HIV susceptibility; the latter effect was related to the restoration of an L. iners-dominated microbiota. Further clinical studies may be needed to assess the impact of BV treatment on HIV acquisition in ACB communities.