Restoration of cytomegalovirus-specific CD4+ T-lymphocyte responses after ganciclovir and highly active antiretroviral therapy in individuals infected with HIV-1

Recent studies of subjects infected with human immunodeficiency virus (HIV-1) have produced conflicting results about the extent of reconstitution possible in the CD4(+) lymphocyte repertoire after highly active antiretroviral therapy(1-3) (HAART). The effect of HAART on the incidence of opportunistic infections will probably depend on reconstitution of antigen-specific CD4(+) lymphocyte responses to important pathogens, including cytomegalovirus (CMV), the leading cause of blindness in AIDS(4-6) Several studies have demonstrated an important role for CD4(+) lymphocytes in controlling CMV replication in vitro and in clinical studies(7-13). It is now possible to quantitate antigen-specific CD4+ lymphocyte responses by flow cytometry(14). Using this method, we studied CMV-specific CD4(+) lymphocyte responses in individuals infected with HIV-1 with and without a history of active CMV-associated end organ disease (EOD), and in those with quiescent CMV EOD after ganciclovir therapy and HAART. The presence of active CMV-associated EOD strongly correlated with loss of CMV-specific lymphocyte responses (P = 0.0004). In contrast, patients with no history of CMV-associated EOD and most patients with quiescent EOD after HAART demonstrated strong CMV-specific CD4(+) lymphocyte responses. These data indicate that the loss of CMV-specific CD4(+) lymphocyte responses in individuals infected with HIV-1 who have active CMV EOD may be restored after ganciclovir therapy and HAART, which provides evidence for functional immune reconstitution to an important pathogen.