Species-level virome profiling reveals compositional differences in the gut prokaryotic DNA virome of people with HIV-1 on antiretroviral therapy

Alterations in the gut bacterial communities are well described in people with HIV-1 (PWH). However, less is known about the gut viral communities (virome). Herein, we performed an exploratory study of the gut DNA virome in PWH receiving antiretroviral therapy (PWH-ART). Virome profiling was performed using two complementary viral taxa identification pipelines, MetaPhlAn4 and Phanta, providing high-resolution taxonomic profiles at the species level. Consistent patterns of the gut DNA virome were obtained with both pipelines, though Phanta identified a greater number of viral taxa at the species level. Most gut DNA viruses were unclassified species, and bacteriophages constituted the majority of identifiable viral populations. Compared to HIV-1 negative controls (n = 11), PWH‑ART (n = 13) exhibited compositional differences in their gut DNA virome at finer taxonomic levels (species and genus), including higher within-group variations and multiple differentially abundant viral taxa. Gender influenced the virome composition, independent of HIV-1 status and age. Furthermore, correlations were identified between multiple unclassified viral species and clinical variables, including gender, CD4+ T cell counts, and ART duration. Further studies are warranted to validate these findings and to elucidate whether the observed compositional differences in the gut DNA virome are mediated by HIV-1 infection itself, by ART, or by both.