Human Immunodeficiency Virus–Infected Patients Receiving Highly Active Antiretroviral Therapy Maintain Activated CD8+ T Cell Subsets as a Strong Adaptive Immune Response to Cytomegalovirus

CD8+ T lymphocyte function specific for human cytomegalovirus (CMV) was evaluated in 14 patients infected with human immunodeficiency virus (HIV) receiving highly active antiretroviral therapy (HAART) and 26 CMV‐seropositive donors without HIV infection. Fifty‐seven percent of the HIV‐infected group had CMV‐specific cytolytic activity in freshly isolated peripheral blood mononuclear cells (PBMC) against targets expressing CMV pp65. Both interferon (IFN)–γ secretion by CD8+ T cells and the frequency of human leukocyte antigen (HLA)–tetramer–positive T cells in HLA‐A*0201–positive HIV‐infected subjects correlated with CMV‐specific cytolysis. In contrast, PBMC from healthy CMV‐seropositive donors did not have either measurable CMV‐specific cytolysis or secretion of IFN‐γ without in vitro stimulation. The T helper response to CMV antigens was vigorous in healthy CMV‐seropositive donors but low in the cohort of HIV‐infected patients. Potent CD8+ cytotoxic T lymphocyte responses to CMV in HIV‐infected patients receiving HAART is the converse of what is found in healthy CMV‐seropositive subjects and may be the predominant adaptive immune response against CMV in HIV‐infected patients.