Human Immunodeficiency Virus Type 1 (HIV-1)-Specific CD4 + T Cells That Proliferate In Vitro Detected in Samples from Most Viremic Subjects and Inversely Associated with Plasma HIV-1 Levels

Abstract

ABSTRACT Diminished in vitro proliferation of human immunodeficiency virus type 1 (HIV-1)-specific CD4 + T cells has been associated with HIV-1 viremia and declining CD4 + T-cell counts during chronic infection. To better understand this phenomenon, we examined whether HIV-1 Gag p24 antigen-induced CD4 + T-cell proliferation might recover in vitro in a group of subjects with chronic HIV-1 viremia and no history of antiretroviral therapy (ART). We found that depletion of CD8 + cells from peripheral blood mononuclear cells (PBMC) before antigen stimulation was associated with a 6.5-fold increase in the median p24-induced CD4 + T-cell proliferative response and a 57% increase in the number of subjects with positive responses. These p24-induced CD4 + T-cell proliferative responses from CD8-depleted PBMC were associated with expansion of the numbers of p24-specific, gamma interferon (IFN-γ)-producing CD4 + T cells. Among the 20 viremic, treatment-naïve subjects studied, the only 5 subjects lacking proliferation-competent, p24-specific CD4 + T-cell responses from CD8-depleted PBMC showed plasma HIV-1 RNA levels > 100,000 copies/ml. Furthermore, both the magnitude of p24-induced CD4 + T-cell proliferative responses from CD8-depleted PBMC and the frequency of p24-specific, IFN-γ-producing CD4 + T cells expanded from CD8-depleted PBMC were associated inversely with plasma HIV-1 RNA levels. Therefore, proliferation-competent, HIV-1-specific CD4 + T cells that might help control HIV-1 disease may persist during chronic, progressive HIV-1 disease except at very high levels of in vivo HIV-1 replication.