In chronically infected HIV-1+ individuals who progress to AIDS, the full functionality of the anti-HIV-1 CD8+ cytotoxic T lymphocyte response is progressively lost. This is accompanied by diminished responses to neo- and recall antigens and skin anergy (loss of DTH response). This is likely dependent on the loss of function and numbers of HIV-1-specific CD4+ helper T lymphocytes (Appay and Sauce 2008). This process is apparently, at least partially, irreversible despite otherwise successful, currently used antiretroviral drug regimens. Accumulation of functionally inert ('anergic') HIV-1-specific CD4+ and CD8+ CD28- CTLA-4hi T cells is observed, which lack proliferative and IL-2 producing ability and cytolytic function despite maintaining the capacity to produce IFN-γ (Deeks and Walker 2007). A balanced response in which the host responds appropriately to prevalent antigen, such as HIV-1 Gag, yet remains relatively quiescent, may prove to be the strongest functional correlate of virologic control (Imami et al. 2002; Imami et al. 2007).