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

Abstract

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/microliter 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.