Analysis of total human immunodeficiency virus (HIV)-specific CD4(+) and CD8(+) T-cell responses: Relationship to viral load in untreated HIV infection

Human immunodeficiency virus (HIV)-specific T-cell responses are thought to play a key role in viral load decline during primary infection and in dete rmining the subsequent viral load set point. The requirements for this effe ct are unknown, partly because comprehensive analysis of total HIV-specific CD4(+) and CD8(+) T-cell responses to all HIV-encoded epitopes has not bee n accomplished. To assess these responses, we used cytokine How cytometry a nd overlapping peptide pools encompassing all products of the HIV-1 genome to study total HIV-specific T-cell responses in 23 highly active antiretrov iral therapy naive HIV-infected patients. HIV-specific CD8(+) T-cell respon ses were detectable in all patients, ranging between 1.6 and 18.4% of total CD8(+) T cells. HIV-specific CD4(+) T-cell responses were present in 21 of 23 patients, although the responses were lower (0.2 to 2.94%). Contrary to previous reports, a positive correlation was identified between the plasma viral load and the total HIV-, Env-, and Nef-specific CD8(+) T-cell freque ncy. No correlation was found either between viral load and total or Gag-sp ecific CD4(+) T-cell response or between the frequency of HIV-specific CD4( +) and CD8(+) T cells. These results suggest that overall frequencies of HI V-specific T cells are not the sole determinant of immune-mediated protecti on in HIV-infection.