HAART reduces death ligand but not death receptors in lymphoid tissue of HIV-infected patients and simian immunodeficiency virus-infected macaques

To determine how antiretroviral therapy (ART) or HAART affects the expression of apoptotic ligands and their death receptors in the blood and lymphoid tissues of HIV-infected patients and simian immunodeficiency virus-infected macaques. We analyzed the mRNA expression of death molecules [tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and FasL] and their receptors (DR5 and Fas) in blood and tonsils from HIV-infected patients (HIV positive), HIV-infected patients receiving HAART and HIV-uninfected (HIV negative) donors in a cross-sectional study. We comparatively analyzed mRNA expression of TRAIL and DR5 in blood and lymph nodes collected longitudinally from simian immunodeficiency virus-infected macaques before and after ART. Expression of TRAIL, FasL, DR5 and Fas was elevated in circulating CD4 T cells from a group of HIV-positive patients as compared with that from both HIV-negative donors and HAART patients. In a different study group, TRAIL, FasL, DR5 and Fas were increased in tonsils of HIV-positive patients as compared with HIV-negative donors and HAART patients. However, tonsils from HAART patients showed reduced expression of TRAIL and FasL but not DR5 and Fas as compared with HIV-positive patients. Similarly, data obtained in a longitudinal study of simian immunodeficiency virus-infected macaques showed that ART reduced both TRAIL and DR5 in peripheral blood but only TRAIL and not DR5 in lymph nodes from the same animals. These findings suggest that HAART or ART is ineffective in reducing the expression of apoptotic death receptors in lymphoid tissue. However, analysis limited to blood leukocytes may not reveal such a defect. Our results highlight the persistence of an underlying immunologic condition that may prevent therapy-induced restoration of CD4 T cells in lymphoid tissue.