CD8(+) lymphocyte responses to antiretroviral therapy of HIV infection

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 supppressor 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/mm(3)), which remained significantly above baseline for 0 to 12 weeks. In contrast, ritonavir monotherapy caused a peak increase of 892 CD8(+) cells/mm(3), 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.