Effects of HIV, Immune Deficiency, and Confounding on the Distal Gut Microbiota

deficiency that manifests as life threatening opportunistic infections and malignancies, i.e., the acquired immune deficiency syndrome (AIDS). The gut mucosa-associated lymphoid tissue (MALT, e.g., Peyer's patches) is a major locus of CD4+ cells. HIV's asymptomatic and insidious destruction of these cells compromises the integrity of the gut mucosa, allowing translocation (leakage) of microbes and other luminal contents into the circulation (Brenchley et al., 2004). Microbial translocation induces subtle but sustained andwidespread immune activation, which is a major contributor to HIV's pathogenesis (Brenchley et al., 2006). Given these effects of HIV on the gut mucosa, it is not surprising that several groups have reported alterations of the gut microbial population (themicrobiota) in peoplewithHIV, including those inwhomHIV iswell controlled with antiretroviral therapy (ART) (Lozupone et al., 2014; Nowak et al., 2015). These studies comprised heterogeneous or poorly defined populations, used various methods, and have been very small — collectively fewer than 100 HIV-infected subjects including those with early HIV, HIV on ART, chronic HIV viremia without ART, and “elite controllers” (non-viremic without ART). In one recent report (Nowak et al., 2015), species-level diversity (termed richness or “alpha diversity”) in feces in 28 HIV viremic patients was significantly lower than in 9 controls; alpha diversity correlated positively with CD4+ cell counts and inversely with plasma markers of microbial translocation and monocyte activation. After ART initiation in these subjects, fecal alpha diversity continued to decrease (Nowak et al., 2015), which corroborates findings from others (Lozupone et al., 2014). In contrast, a more recent and comprehensive study (Mutlu et al., 2014) reported that fecal alpha diversity did not differ between 21HIV-infected subjects and 22 demographically similar, HIV-uninfected controls, although their HIV subjects did have significantly lower alpha diversity in multiple