The mechanism of CD4+ T-cell depletion remains a central unresolved issue in AIDS research. Recent studies have examined the massive depletion of CD4+ T cells observed in macaque models of acute HIV infection. A key question is whether the observed CD4+ T-cell death is due to direct consequences of viral infection and to indirect mechanisms including increased expression of mediators of T-cell apoptosis. The therapeutic implications of the early CD4+ T-cell loss are discussed.
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