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.