HIV-infected immunological non-responders have colon-restricted gut mucosal immune dysfunction.

Background HIV-infected immunological non-responders (INR) fail to reconstitute their CD4 + T cell pool after initiation of antiretroviral therapy, and their prognosis is inferior to the immunological responders (IR). A prevailing hypothesis is that the INR phenotype is caused by a persistently disrupted mucosal barrier, but assessments of gut mucosal immunology in different anatomical compartments are scarce. Methods We investigated circulating markers of mucosal dysfunction, immune activation, mucosal Th17 and Th22 cells, and mucosa-adherent microbiota signatures in gut mucosal specimens from sigmoid colon and terminal ileum of 19 INR and 20 IR in addition to 20 HIV negative individuals. Results INR had higher blood levels of the enterocyte damage marker Intestinal fatty acid binding protein (I-FABP) than IR. In gut mucosal biopsies, INR had lower fractions of CD4 + T cells, higher fractions of IL-22, and a tendency to higher fractions of IL-17 producing CD4 + T cells. These findings were all restricted to the colon and correlated to circulating markers of enterocyte damage. There were no observed differences in gut microbial composition between INR and IR. Conclusion Restricted to the colon, enterocyte damage and mucosal immune dysfunction play a role for insufficient immune reconstitution in HIV infection independently of the gut microbiota.