Association Between Gut Microbiota and CD4 Recovery in HIV-1 Infected Patients

Composition of the gut microbiota has been linked with human immunedeficiency virus (HIV)-infected patients on antiretroviral therapy (ART). Evidence suggests that ART-treated patients with poor CD4⁺ T-cell recovery have higher levels of microbial translocation and immune activation. However, the association of the gut microbiota and immune recovery remains unclear. We performed a cross-sectional study on 30 healthy controls (HC) and 61 HIV-infected individuals, including 15 immunological ART responders (IRs), 20 immunological ART non-responders (INRs) and 26 untreated individuals (VU). IR and INR groups were classified by CD4⁺ T-cell counts of ≥350 cells/mm³ and <350 cells/mm³ after 2 years of ART, respectively. Each subject's gut microbiota composition was analyzed by metagenomics sequencing. Levels of CD4⁺ T cells, CD8⁺HLA-DR⁺ T cells and CD8⁺CD38⁺ T cells were measured by flow cytometry. We identified more <i>Prevotella</i> and fewer <i>Bacteroides</i> in HIV-infected individuals than in HC. Patients in INR group were enriched with <i>Faecalibacterium prausnitzii</i>, unclassified <i>Subdoligranulum sp.</i> and <i>Coprococcus comes</i> when compared with those in IR group. <i>F. prausnitzii</i> and unclassified <i>Subdoligranulum sp.</i> were overrepresented in individuals in VU group with CD4⁺ T-cell counts <350 cells/mm³. Moreover, we found that the relative abundance of unclassified <i>Subdoligranulum sp.</i> and <i>C. comes</i> were positively correlated with CD8⁺HLA-DR⁺ T-cell count and CD8⁺HLA-DR⁺/CD8⁺ percentage. Our study has shown that gut microbiota changes were associated with CD4⁺ T-cell counts and immune activation in HIV-infected subjects. Interventions to reverse gut dysbiosis and inhibit immune activation could be a new strategy for improving immune reconstitution of HIV-1-infected individuals.