Decreased T cell apoptosis and T cell recovery during highly active antiretroviral therapy (HAART)

T cell apoptosis represents a common mechanism of T cell depletion in HIV-1-infected individuals reflecting maturational and functional T cell abnormalities either directly or indirectly induced by the virus. In the present study, the effects of highly active antiretroviral therapy (HAART) on the spontaneous apoptosis of distinct T cell subsets were investigated during a 6-month follow-up in a cohort of HIV-1-infected individuals with CD4⁺ cell counts between 100 and 500 cells/μl and plasma HIV-1 RNA levels ≥10,000 copies/ml. We determined that the rapid and sustained increase of both naive (CD45RA⁺CD62L⁺) and memory (CD45R0⁺ and CD45RA⁺/CD62L^-) CD4⁺ and, to as lesser extent, CD8⁺ T cells in peripheral blood was associated with a significant decrease of apoptotic CD4⁺ and CD8⁺ as well as CD3⁺CD4^-CD8^- T cells. Among CD4⁺ lymphocytes, at enrollment, the highest frequency of apoptotic cells was observed within the memory compartment, as defined by CD45R0 expression. During HAART, however, the frequency of CD4⁺CD45R0⁺ apoptotic T cells progressively decreased in association with a significant downregulation of surface activation markers that indicated decreased levels of systemic immune stimulation. These results indicate that effective viral suppression can contribute to progressive normalization of maturational and functional T cell abnormalities responsible for the high levels of T cell apoptosis in HIV-1-infected individuals. This, in turn, may contribute to a reduced rate of T cell loss and immune reconstitution during HAART. (C) 2000 Academic Press.