Our purpose was to determine if changes in CD4 cell counts in HIV-infected patients with good viral suppression on stable antiretroviral regimens could be predicted by ex-vivo rates of apoptosis of peripheral blood mononuclear cells (PBMC). Patients were grouped by lowest pre-treatment and highest on-treatment CD4 cell counts and classified as complete immune responders, partial responders, or non-responders. Whole blood was collected from a subgroup of patients and controls, and rates of the ex-vivo apoptosis of PBMC were assessed. Non-responders exhibited significantly increased apoptosis, whereas good immune responses were associated with decreased apoptosis. Persistently accelerated apoptosis may contribute to persisting immune deficiency independent of the viral load.