Restoration of cytomegalovirus-specific CD4+ T-lymphocyte responses after ganciclovir and highly active antiretroviral therapy in individuals infected with HIV-1
Krishna V. Komanduri1, 2, Mohan N. Viswanathan1, Eric D. Wieder1, Diane K. Schmidt1, Barry M. Bredt3, Mark A. Jacobson4
& Joseph M. McCune1, 3, 4, 5
1Gladstone Institute of Virology and Immunology, P.O. Box 419100, San Francisco, CA 94141-9100
2Division of Hematology & Oncology, University of California, San Francisco
3General Clinical Research Center, San Francisco General Hospital, University of California, San Francisco
4The AIDS Program, San Francisco General Hospital, and the Department of Medicine, University of California, San Francisco
5Correspondence should be addressed to J.M.M.
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 therapy1−3 (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 AIDS4−6. Several studies have demonstrated an important role for CD4+ lymphocytes in controlling CMV replication in vitro and in clinical studies7−13. It is now possible to quantitate antigen-specific CD4+ lymphocyte responses by flow cytometry14. 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.
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