To our knowledge our study is the first study showing persistent apoptosis in a subgroup of patients with complete viral suppression in association with poor immune recovery. Immune alterations independent of active viral replication may be responsible. Recent data suggests that immune responses to antiretroviral therapy depend on residual or restored thymic function. Improved CD4+ counts in patients despite virologic treatment failure are associated with greater thymic function, while poor T cell responses despite suppression of HIV are seen with decreased thymic function. Discordant immune responses may also be due to differential effects of particular antiretroviral agents on T cell apoptosis independent of viral suppression. For example, protease inhibitors have been shown to decrease rates of apoptosis of uninfected T cells. Viral replication is never completely suppressed with HAART, even when patients have undetectable plasma HIV RNA. Therefore, varying degrees of low level viral replication or replication in certain cellular compartments may continue to drive T cell apoptosis. Finally, our data suggests that ex vivo rates of Peripheral blood mononuclear cell (PBMC) apoptosis could potentially be used predict immune recovery or identify subgroups of patients who may benefit most from changes in HAART or adjunctive immunomodulatory therapies.