Changes in intestinal microbiota in HIV-1-infected subjects following cART initiation: influence of CD4+ T cell count

The roles of immunodeficiency and combined antiretroviral therapy (cART) in shaping the gut microbiota in HIV-1-infected subjects (HISs) have not been described thoroughly by time-series investigations. In this study, 36 antiretroviral-naïve HISs were enrolled to prospectively assess alterations in the fecal microbiota and plasma markers of microbial translocation and inflammation with cART. At baseline, the species α-diversity of the fecal microbiota was significantly lower in HISs with a CD4⁺ T cell count &lt;300/mm³ than in HISs with a CD4⁺ T cell count &gt;300/mm³ (Shannon index: Median 2.557 vs. 2.981, <i>P</i> = 0.006; Simpson index: Median 0.168 vs. 0.096, <i>P</i> = 0.004). Additionally, the baseline α-diversity indices correlated with CD4⁺ T cell counts (Shannon index: <i>r</i> = 0.474, <i>P</i> = 0.004; Simpson index: <i>r</i> = −0.467, <i>P</i> = 0.004) and the specific plasma biomarkers for microbial translocation and inflammation. After cART introduction, the species α-diversity of fecal microbiota in HISs with CD4⁺ T cell counts &lt;300/mm³ was significantly restored (Shannon index: Median 2.557 vs. 2.791, <i>P</i> = 0.007; Simpson index: Median 0.168 vs. 0.112, <i>P</i> = 0.004), while the variances were insignificant among HISs with CD4+ T cell counts &gt;300/mm³ (Shannon index: Median 2.981 vs. 2.934, <i>P</i> = 0.179; Simpson index: Median 0.096 vs. 0.119, <i>P</i> = 0.082). Meanwhile, with cART introduction, alterations in the gut microbial composition were more significant in the subgroup with CD4⁺ T cell counts &gt;300/mm³, corresponding to increases in the specific plasma inflammatory markers. These findings implicated the interactive roles of immunodeficiency and cART for affecting gut microbiota in HIV-1-infected individuals, providing new insights into intestinal microbiome dysbiosis related to HIV-1 infection.