Alterations of the gut microbiome in HIV infection highlight human anelloviruses as potential predictors of immune recovery.

Background: HIV-1 infection is characterized by a massive depletion of mucosal CD4 T cells that triggers a cascade of events ultimately linking gut microbial dysbiosis to HIV-1 disease progression and pathogenesis. The association between HIV infection and the enteric virome composition is less characterized, although viruses are an essential component of the gut ecosystem. Here, we performed a cross-sectional analysis of the fecal viral (eukaryotic viruses and bacteriophages) and bacterial microbiome in people with HIV (PWH) and in HIV-negative individuals. To gain further insight into the association between the gut microbiome composition, HIV-associated immunodeficiency, and immune recovery, we carried out a longitudinal study including 14 PWH who initiated antiretroviral therapy (ART) and were followed for 24 months with samplings performed at baseline (before ART) and at 2, 6, 12, and 24 months post-ART initiation.

Results: Our data revealed a striking expansion in the abundance and prevalence of several human virus genomic sequences (Anelloviridae, Adenoviridae, and Papillomaviridae) in stool samples of PWH with severe immunodeficiency (CD4 < 200). We also noted a decreased abundance of sequences belonging to two plant viruses from the Tobamovirus genus, a reduction in bacterial alpha diversity, and a decrease in Inoviridae bacteriophage sequences. Short-term ART (24 months) was linked to a significant decrease in human Anelloviridae sequences. Remarkably, the detection of Anellovirus sequences at baseline independently predicted poor immune recovery, as did low CD4 T cell counts. The bacterial and bacteriophage populations were unique to each PWH with individualized trajectories; we found no discernable pattern of clustering after 24 months on ART.

Conclusion: Advanced HIV-1 infection was associated with marked alterations in the virome composition, in particular a remarkable expansion of human anelloviruses, with a gradual restoration after ART initiation. In addition to CD4 T cell counts, anellovirus sequence detection might be useful to predict and monitor immune recovery. This study confirms data on the bacteriome and expands our knowledge on the viral component of the gut microbiome in HIV-1 infection. Video Abstract.