PATTERNS OF T-CELL REPOPULATION, VIRUS LOAD REDUCTION, AND RESTORATION OF T-CELL FUNCTION IN HIV-INFECTED PERSONS DURING THERAPY WITH DIFFERENT ANTIRETROVIRAL AGENTS

The effect of antiretroviral therapy on both T-cell numbers and T-cell function in peripheral blood was studied. CD4(+) and CD8(+) T-cell nu mbers, T-cell reactivity to CD3 monoclonal antibodies (mAb), and viral RNA load date were obtained from patients treated for at least 28 wee ks with either the HIV-1 protease inhibitor ritonavir, the nonnucleosi de HIV-1 reverse transcriptase (RT) inhibitor nevirapine, or the nucle oside analogue RT inhibitor zidovudine, Compared with both RT inhibito rs, treatment with the protease inhibitor ritonavir resulted in the mo st significant and persistent elevation of CD4(+) and CD8(+) T-cell co unts. However, in vitro T-cell functional improvement was of limited d uration in the ritonavir-treated group and was inversely correlated wi th viral RNA load changes during the entire follow-up period. Thus, de spite what can be assumed of responses during RT inhibitor therapy, qu antitative responses on therapy did not necessarily correlate with qua litative immunologic responses, as can be seen during treatment with r itonavir. For optimal immune reconstitution, both numeric and function al immunologic improvements are essential. During antiretroviral thera py, measurement of in vitro improvement in immune function will be use ful as a correlate for transient drug-induced alteration of immunodefi ciency.