RESTORATION OF CYTOMEGALOVIRUS-SPECIFIC CD4(-LYMPHOCYTE RESPONSES AFTER GANCICLOVIR AND HIGHLY-ACTIVE ANTIRETROVIRAL THERAPY IN INDIVIDUALSINFECTED WITH HIV-1() T)

Recent studies of subjects infected with human immunodeficiency virus (HIV-1) have produced conflicting results about the extent of reconsti tution possible in the CD4(+) lymphocyte repertoire after highly activ e antiretroviral therapy(1-3) (HAART). The effect of HAART on the inci dence of opportunistic infections will probably depend on reconstituti on of antigen-specific CD4(+) lymphocyte responses to important pathog ens, including cytomegalovirus (CMV), the leading cause of blindness i n AIDS(4-6) Several studies have demonstrated an important role for CD 4(+) lymphocytes in controlling CMV replication in vitro and in clinic al studies(7-13). It is now possible to quantitate antigen-specific CD 4+ lymphocyte responses by flow cytometry(14). Using this method, we s tudied CMV-specific CD4(+) lymphocyte responses in individuals infecte d with HIV-1 with and without a history of active CMV-associated end o rgan disease (EOD), and in those with quiescent CMV EOD after ganciclo vir therapy and HAART. The presence of active CMV-associated EOD stron gly correlated with loss of CMV-specific lymphocyte responses (P = 0.0 004). In contrast, patients with no history of CMV-associated EOD and most patients with quiescent EOD after HAART demonstrated strong CMV-s pecific CD4(+) lymphocyte responses. These data indicate that the loss of CMV-specific CD4(+) lymphocyte responses in individuals infected w ith HIV-1 who have active CMV EOD may be restored after ganciclovir th erapy and HAART, which provides evidence for functional immune reconst itution to an important pathogen.