Association of strong virus-specific CD4 T cell responses with efficient natural control of primary HIV-1 infection.

OBJECTIVE:To investigate whether there are differences in the virus-specific CD4 T cell response during primary HIV-1 infection in patients who naturally (without antiretroviral intervention) control viral replication with differing efficiencies. METHODS:CD4 T cell responses to recombinant HIV proteins (Gag p24 and p55 and Env gp160) and an inactivated HIV-1 preparation were analysed using interferon-gamma ELISPOT assays (with CD8-depleted peripheral blood mononuclear cells) and by intracellular interferon-gamma staining and fluorescent-activated cell sorting. RESULTS:Strong HIV-specific CD4 T cell responses were detected from the earliest time-points analysed in primary infection in patients who naturally established low persisting viral loads. By contrast, HIV-specific CD4 T cell responses were weaker (at or just below the limit of detection in our assays) at similar time-points in patients who went on to establish high persisting viral loads. Statistical analysis revealed a highly significant difference (P < 0.001) between the magnitudes of the Gag p24-specific response at the earliest time-point analysed in primary infection in the two sets of patients. CONCLUSIONS:Strong HIV-specific CD4 T cell responses are associated with efficient natural control of primary HIV-1 infection.