Longitudinal cervicovaginal bacteriome and virome alterations associate with discordant shedding and ART duration in women living with HIV in Peru

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) bacterial and viral microbiome (bacteriome and virome) community dynamics during long-term ART in WLHIV are poorly understood but might contribute to discordant HIV shedding, as the bacteriome and virome are known to influence FGT health. Here, using metagenomic next-generation sequencing, we characterize the bacteriome and virome in 125 cervicovaginal specimens collected over two years from 31 WLHIV in Lima, Peru, and show that FGT bacteriome instability is associated with discordant HIV shedding, while longitudinal changes in FGT virome composition are associated with ART duration. Intrapersonal bacteriome variation is higher in discordant HIV shedders compared to non-shedders. Cervicovaginal virome composition changes over time, particularly in non-shedders. Specifically, anellovirus relative abundance is inversely associated with ART duration and CD4 counts. Our results suggest that discordant HIV shedding is linked with FGT bacteriome instability, and immune recovery during ART influences FGT virome composition.