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 (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. Several studies have demonstrated an important role for CD4+ lymphocytes in controlling CMV replication in vitro and in clinical studies. It is now possible to quantitate antigen-specific CD4+ lymphocyte responses by flow cytometry. 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.
Komanduri
K V
KV
Gladstone Institute of Virology and Immunology, San Francisco, CA 94141-9100, USA.
Viswanathan
M N
MN
Wieder
E D
ED
Schmidt
D K
DK
Bredt
B M
BM
Jacobson
M A
MA
McCune
J M
JM
D017088:AIDS-Related Opportunistic Infections / Q000276:immunology*; D000998:Antiviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology*; D002478:Cells, Cultured; D015331:Cohort Studies; D017726:Cytomegalovirus Retinitis / Q000188:drug therapy* / Q000276:immunology*; D005434:Flow Cytometry; D015774:Ganciclovir / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D008137:Longitudinal Studies; D008213:Lymphocyte Activation
D000998:Antiviral Agents; D015774:Ganciclovir