Simian immunodeficiency virus infection induces severe loss of intestinal central memory T cells which impairs CD4⁺ T-cell restoration during antiretroviral therapy

Background: Simian immunodeficiency virus (SIV) infection leads to severe loss of intestinal CD4⁺ T cells and, as compared to peripheral blood, restoration of these cells is slow during antiretroviral therapy (ART). Mechanisms for this delay have not been examined in context of which specific CD4⁺ memory subsets or lost and fail to regenerate during ART. Methods: Fifteen rhesus macaques were infected with SIV, five of which received ART (FTC/PMPA) for 30 weeks. Viral loads were measured by real-time PCR. Flow cytometric analysis determined changes in T-cell subsets and their proliferative state. Results: Changes in proliferative CD4⁺ memory subsets during infection accelerated their depletion. This reduced the central memory CD4⁺ T-cell pool and contributed to slow CD4⁺ T-cell restoration during ART. Conclusion: There was a lack of restoration of the CD4⁺ central memory and effector memory T-cell subsets in gut-associated lymphoid tissue during ART, which may contribute to the altered intestinal T-cell homeostasis in SIV infection.