Longitudinal cervicovaginal microbiome and virome alterations during ART and discordant shedding in women living with HIV.

Despite successful suppression of plasma HIV replication by antiretroviral therapy (ART), some women living with HIV (WLHIV) can still experience genital HIV shedding (discordant shedding). Female genital tract (FGT) microbiome and virome dynamics during long-term ART in WLHIV are poorly understood but might contribute to discordant HIV shedding, as the microbiome and virome are known to influence FGT health. To understand FGT microbial communities over time during ART usage and discordant shedding, we characterized the microbiome and virome in 125 cervicovaginal specimens collected over two years in 31 WLHIV in Lima, Peru. Intrapersonal bacterial microbiome variation was higher in HIV shedders compared to non-shedders. Cervicovaginal virome composition changed over time, particularly in non-shedders. Specifically, anellovirus relative abundance was inversely associated with ART duration and CD4 counts. Our results suggest that discordant HIV shedding is associated with FGT microbiome instability, and immune recovery during ART influences FGT virome composition.