Cervicovaginal microbiota not dominated by lactobacilli are associated with HIV viral shedding in African female sex workers

Background. Cervicovaginal microbiota may influence HIV shedding in the genital tract of HIV positive women and onward transmission to their sex partners. Methods. The HIV-1 RNA concentration (lower limit of detection 40 copies/ml) was measured cross-sectionally in cervicovaginal lavages of 108 HIV-positive women from a well-characterised cohort of female sex workers Kigali, Rwanda. Cervical samples of 49 of these women were also evaluated by a phylogenetic microarray specifically designed to characterise the cervicovaginal microbiome. 251 probes were used for co-regularised spectral clustering analysis and 123 probes (specific at species or genus level) to describe microbiome compositions. Results. Six microbiome clusters were identified, representing a gradient from low (semi-quantitative) bacterial load and diversity dominated by Lactobacillus crispatus (R-I) and L. iners (R-II), to intermediate bacterial load and diversity (R-V), to high bacterial load and diversity (R-III, R-IV, and R-VI) dominated by a mixture of (facultative) anaerobes. A statistically significant trend was observed with 10% of women in clusters R-I/R-II, 40% of women in cluster R-V, and 42.1% of women in cluster R-III/R-IV/R-VI having detectable HIV-1 RNA (p trend 0.03). Positive correlations were found between HIV-1 RNA concentrations and (semi-quantitative) levels of Prevotella spp. (spearman rho 0.4, p 0.002), Sneathia spp. (rho 0.38, p 0.003) and Dialister spp. (rho 0.36, p 0.006). Lactobacillus was the only genus with a negative correlation with HIV-1 RNA levels (rho 0.37, p 0.005). These associations remained significant when adjusted for CD4 count. In bivariable analysis, other factors associated with detectable genital HIV-1 RNA levels were not using antiretroviral therapy (ART), genital itching, other specific genital symptoms, abundant cervical mucus on pelvic exam, HPV infection (but not HSV-2 antibodies), and bacterial vaginosis by Nugent scoring. Microbiome clustering was not associated with ART. Conclusion. In this group of HIV-positive sex workers, cervicovaginal microbiota that were not dominated by lactobacilli were associated with cervicovaginal HIV-shedding, which was not mediated by CD4 count