HIV-specific immune responses in acute infection early disease (AIED) may be effective at controlling viral replication and in establishing viral load (VL) set point. However, evidence correlating the function and specificity of these responses with the VL set point is lacking. To address this issue, we screened cells from 59 treatment-naïve HIV infected individuals (33 in AIED and 26 progressors) for responses to the entire HIV proteome using a dual color ELISPOT assay detecting 3 functional lymphocyte populations: single IFN-gamma, dual IFN-gamma/IL-2 and single IL-2 secreting cells. Responses characterized by dual secreting cells contributed more to the HIV specific response in AIED versus chronic infection. Of responses directed to individual HIV gene products the magnitude and breadth of only Gag p24-specific responses for the 3 functional subsets were associated with lower concurrent or set point VL. Therefore the early appearance of broader and more intense Gag-p24-specific responses may be a determinant of subsequent VL.