Loss of CD4+ T Cell Proliferative Ability but Not Loss of Human Immunodeficiency Virus Type 1 Specificity Equates with Progression to Disease

In this study, we compared human immunodeficiency virus (HIV) type 1—specific proliferative responses with HIV-1—induced intracellular cytokine production in a cohort of clinically nonprogressing patients and individuals with progressive HIV-1 infection. We found strong HIV-1—specific proliferative responses in the clinical nonprogressor cohort that correlated with significant numbers of circulating HIV-1—specific CD4+ T cells. In contrast, HIV-1—specific proliferative responses were absent in most individuals with progressive HIV-1 infection, even though interferon-γ—producing HIV-1—specific CD4+ T cells were detectable by flow cytometry. The implication of these data is that the important dysfunction seen in most HIV-positive patients from very early in disease may be an inability of HIV-1—specific CD4+ memory T cells to proliferate in response to HIV antigens rather than an absolute loss of circulating virus—specific CD4+ T cells.