HIV+ elite controllers have low HIV-specific T-cell activation yet maintain strong, polyfunctional T-cell responses.

OBJECTIVE: HIV elite controllers are a unique group of rare individuals who maintain undetectable viral loads in the absence of antiretroviral therapy. We studied immune responses in these individuals to inform vaccine development, with the goal of identifying the immune correlates of protection from HIV. METHODS: We compared markers of cellular activation, HIV-specific immune responses and regulatory T (Treg) cell frequencies in four groups of individuals: HIV-negative healthy controls, elite controllers (HIV RNA level <75 copies/ml), individuals on HAART and individuals with HIV RNA level more than 10,000 copies/ml (noncontrollers). RESULTS: Elite controllers possessed significantly lower levels of activated HIV-specific CD8 T cells and of recently divided HIV-specific CD4 T cells than noncontrollers, whereas these differences were not seen in the respective cytomegalovirus-specific T-cell populations. Elite controllers also mounted a stronger and broader cytokine and chemokine response following HIV-specific stimulation than individuals on HAART and noncontrollers. Finally, we found that HAART-suppressed individuals had elevated Treg cell frequencies, whereas elite controllers and noncontrollers maintained normal percentages of Treg cells. CONCLUSION: Elite controllers maintain high levels of HIV-specific immune responses with low levels of HIV-specific T-cell activation and do not have elevated Treg cell levels. Based on these data an ideal HIV vaccine would induce strong HIV-specific immune responses whereas minimizing HIV-specific T-cell activation.