Bacterial dysbiosis, cervicovaginal human papillomaviruses and inflammation persist in women living with HIV-1 after a year of antiretroviral treatment.

Abstract

The cervicovaginal microbiome may affect HIV-1 susceptibility and can in turn influence the prevalence and clinical course of HIV-1 and other sexually transmitted diseases. As the determinants, immunological correlates and clinical effects of the dysbiosis observed in women living with HIV-1 (WWH) remain elusive, we evaluated the vaginal immunologic milieu, cervicovaginal microbiome and prevalence of human papillomaviruses (HPV) in antiretroviral-naïve WWH over their first year of antiretroviral therapy (ART). 83 ART-naïve Ugandan WWH were enrolled in a longitudinal observational trial. Clinical evaluation and sampling of cervicovaginal secretions and plasma were performed at 0, 8, 24 and 52 weeks post-ART initiation. Amplification of the 16S-rRNA gene V3-V4 region was used to determine the cervicovaginal microbiome. A multiplex bead-array assay was used to quantify the concentration of biomarkers while a PCR-based hybridization assay was utilized for HPV detection and genotyping. Gardnerella was the most abundant genus with a median relative abundance of 35% before ART maintaining a high prevalence throughout the study. Vaginal bacterial diversity did not change after ART, although the relative abundance of some genera, including the bacterial-vaginosis-associated bacteria Peptostreptococcus and Prevotella, decreased compared to baseline. Inflammatory biomarkers remained elevated in the cervicovaginal compartment despite prompt decreases in plasma.The prevalence of high and low-risk HPV types remained stable despite ART. Suppression of HIV-1 replication is not sufficient to revert dysbiotic changes, proinflammatory immunological milieu and persistent HPV infections. Exploration of targeted strategies to restore cervicovaginal mucosal immunological functions in WWH is warranted.