In the present study, we assessed whether Gag-specific interferon (IFN)-gamma secreting responses correlate with the rate of disease progression as defined by the annual rate of CD4 decline. Although neither the breadth nor the magnitude of the proteome-wide HIV-specific IFN-gamma response correlated with viral load or rate of CD4 decline, the preferential targeting of Gag is associated with slower annual CD4 T cell decline.