Persistence of Bacterial Dysbiosis, Cervicovaginal Human Papillomaviruses, and Inflammation in Women Living With HIV-1 After a Year of Antiretroviral Therapy.

BACKGROUND: The cervicovaginal microbiome may affect susceptibility to human immunodeficiency virus (HIV) -1 and can in turn influence the prevalence and clinical course of HIV-1 and other sexually transmitted diseases. Because the determinants, immunological correlates, and clinical effects of the dysbiosis observed in women with HIV-1 (WWH) remain elusive, we evaluated the vaginal immunological milieu, cervicovaginal microbiome, and prevalence of human papillomaviruses (HPVs) in antiretroviral-naive WWH over their first year of antiretroviral therapy (ART).

METHODS: 83 ART-naive Ugandan WWH were enrolled in a longitudinal observational trial. Clinical evaluation and sampling of cervicovaginal secretions and plasma were performed 0, 8, 24, and 52 weeks after ART initiation. 16S ribosomal-RNA-V3-V4 sequencing identified cervicovaginal microbial communities. A multiplex-bead-array assay was used for biomarkers quantification, while a polymerase chain reaction-based hybridization assay was used for HPV genotyping.

RESULTS: 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 with baseline. Inflammatory biomarkers remained elevated in the cervicovaginal compartment despite prompt decreases in plasma. The prevalence of high-risk and low-risk HPV types remained stable despite ART.

CONCLUSIONS: 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.