Impact of short-term antiretroviral therapy during early HIV infection on microbial translocation, gut immunology and biomarkers of serious non-AIDS illnesses

HIV infection is characterized by the simultaneous reduction of mucosal Th22 cell numbers and Th17 cell function, and impaired epithelial integrity leading to inflammation and serious non-AIDS illnesses (SNAs).  We examined the impact of antiretroviral therapy (ART) initiated during early HIV infection (N=22) on mucosal immune function (Th17 and Th22 cells), gut IL-22 signaling, and blood biomarkers of epithelial integrity (I-FABP), microbial translocation (LPS) and SNAs (IL-6 and D-dimer).  Prior to ART, gut Th22 cell number and Th17 functionality (ability to co-produce IL-22, IFNg and TNFa) were reduced compared to HIV-uninfected controls, and plasma levels of LPS, I-FABP, IL-6 and D-dimer were elevated.  After ART initiation, gut Th22 cell numbers were restored, but there was no change in gut Th17 function or plasma LPS and IL-6 levels, and blood D-dimer and I-FABP levels actually increased. Immunofluorescence microscopy demonstrated decreased expression of IL-22 receptor on gut epithelial cells after ART, which we hypothesize may impair IL-22 signal transduction and epithelial repair.  Therefore, early HIV infection was associated with substantial gut mucosal immune dysfunction, microbial translocation and systemic inflammation, and short-term ART had a limited impact on these parameters.