Gut virome in HIV infection

The gastrointestinal tract is a major site of HIV replication, resulting in a massive depletion of mucosal CD4 T cells in the small and large intestine during both acute and chronic phases of HIV infection. Here we characterized the gut virome at different stages of HIV infection and after antiretroviral therapy (ART) initiation. We used metagenomic viral sequencing to describe the RNA and DNA virome in stool samples from 145 individuals in Mexico, including 53 HIV-negative subjects and 92 people living with HIV (PLWH). Low CD4 T cell counts were associated with an expansion of human virus sequences belonging to the families Anelloviridae, Adenoviridae and Papillomaviridae as well as a depletion of the plant viruses PMMoV and TSAMV. These alterations of the gut virome in PLWH with severe immunodeficiency were progressivley reduced after ART initiation. Notably, both low baseline CD4 T cell counts and detection of human Anelloviridae sequences in stool samples before cART initiation independently predicted poor immune recovery. Thus, the expansion of some human viruses such as anelloviruses in stool samples from PLWH may be a marker of the immune status and a predictor of immune recovery after ART initiation.