title: CD8+ lymphocyte responses to antiretroviral therapy of HIV infection.
abstract: CD8+ T lymphocytes may mediate important host responses to human immunodeficiency virus (HIV) infection by human leukocyte antigen (HLA)-restricted cytotoxicity and production of soluble HIV suppressor factors. CD8+ lymphocytes are also important for the suppression of many latent pathogens responsible for opportunistic disease in HIV-infected patients. There has been no systematic analysis of the responses of CD8+ lymphocyte counts to antiretroviral therapy. We compared CD8+ lymphocyte responses in seven trials of nucleoside or non-nucleoside analog reverse transcriptase inhibitors and in two trials of ritonavir, a HIV protease inhibitor. Nucleoside analog and non-nucleoside analog reverse transcriptase inhibitor monotherapy resulted in no substantial changes in CD8+ counts relative to baseline or placebo. Combination nucleoside analog therapy resulted in variable peak responses (-145 to +240 cells/mm3), which remained significantly above baseline for 0 to 12 weeks. In contrast, ritonavir monotherapy caused a peak increase of 892 CD8+ cells/mm3, which remained significantly above baseline for 32 weeks. There was a significant correlation (Rs 0.61, p = 0.01) between the peak CD4+ cell and CD8+ responses to each therapy, but no significant correlation between the peak viral load responses and peak CD8+ cell responses. These findings suggest that the greater CD8+ response seen with ritonavir may be due to its specific inhibition of HIV protease and also that the CD8+ response is dependent on new CD4+ cell production. The CD8+ lymphocyte proliferation observed with protease inhibitor therapy could result in improved suppression of HIV replication by the immune system and should be confirmed in a prospective trial comparing protease inhibitors with both nucleoside and non-nucleoside analog therapies.
authors.affiliation: HIV Medicine Unit, St. Vincent's Hospital, Sydney, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Carr
authors.forename: S
authors.initials: S
authors.lastname: Emery
authors.forename: A
authors.initials: A
authors.lastname: Kelleher
authors.forename: M
authors.initials: M
authors.lastname: Law
authors.forename: D A
authors.initials: DA
authors.lastname: Cooper
mesh_terms: D000081:Acetamides / Q000627:therapeutic use; D000098:Acetophenones / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016049:Didanosine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D018655:Lymphocyte Count; D011725:Pyridines / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use; D019562:Viral Load; D016047:Zalcitabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D000081:Acetamides; D000098:Acetophenones; D017320:HIV Protease Inhibitors; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; C080073:loviride; D015215:Zidovudine; D016047:Zalcitabine; C050624:2',3'-dideoxycytidinene; D054303:HIV Reverse Transcriptase; D016049:Didanosine; D019438:Ritonavir