Patterns of T-cell repopulation, virus load reduction, and restoration of T-cell function in HIV-infected persons during therapy with different antiretroviral agents

Abstract

The effect of antiretroviral therapy on both T-cell numbers and T-cell function in peripheral blood was studied. CD4+ and CD8+ T-cell numbers, T-cell reactivity to CD3 monoclonal antibodies (mAb), and viral RNA load date were obtained from patients treated for at least 28 weeks with either the HIV-1 protease inhibitor ritonavir, the nonnucleoside HIV-1 reverse transcriptase (RT) inhibitor nevirapine, or the nucleoside-analogue RT inhibitor zidovudine. Compared with both RT inhibitors, treatment with the protease inhibitor ritonavir resulted in the most significant and persistent elevation of CD4+ and CD8+ T-cell counts. However, in vitro T-cell functional improvement was of limited duration in the ritonavir-treated group and was inversely correlated with viral RNA load changes during the entire follow-up period. Thus, despite what can be assumed of responses during RT inhibitor therapy, quantitative responses on therapy did not necessarily correlate with qualitative immunologic responses, as can be seen during treatment with ritonavir. For optimal immune reconstitution, both numeric and functional immunologic improvements are essential. During antiretroviral therapy, measurement of in vitro improvement in immune function will be useful as a correlate for transient drug-induced alteration of immunodeficiency.