We conducted an international multi-centre randomized placebo-controlled clinical trial of oral ritonavir 600 mg twice daily, which has shown clinical efficacy in prevention of death and of new or specific recurrent AIDS-defining events. 1090 HIV patients with under 101 CD4 T cells/mm3 and over nine months prior anti-HIV therapy were randomized and followed-up for sixteen weeks, before any ritonavir crossover for AIDS outcomes was begun. Of the first 211 patients enrolled we analyzed the first 159 patients with over 15,000 HIV RNA particles/mL plasma by quantitative PCR for virology substudy. We compared the dynamics of plasma HIV RNA, CD4 and CD8 T cell counts to ritonavir, and in comparison with placebo patients, at baseline, 2, 4, 8, 12, and 16 weeks. Baseline measures in ritonavir group patients were mean 5.3 log10 RNA particles/mL plasma, 31 CD4 T cells/mm3, and 506 CD8 T cells/mm3. Trough level of plasma RNA was at baseline in 2.6%, at 2 weeks in 34%, and at 4 weeks in another 22% of ritonavir patients. Time to maximal mean decrease from baseline in the ritonavir group, and maximal difference between ritonavir and placebo groups was 2 weeks, for 1.3 log10 RNA particles/mL plasma (p less than 0.001). Peak CD8 T cell count response was at baseline in 12.6%, 2 weeks in 8.7%, 4 weeks in 16.5%, and at 8 weeks another 35% of ritonavir patients. Time to maximal mean increase from baseline was 8 weeks (mean 314 +/- SE 43 CD8 cells/mm3, p less than 0.001). Time to maximal difference between ritonavir and placebo groups was eight weeks (363 +/- 61 CD8 cells/mm3, p less than 0.001). Peak CD4 T cell count response in ritonavir patients was at baseline in 6%, at 2 weeks in 16%, at 4 weeks in 16%, at 8 weeks in 19%, at 12 weeks in 16%, and at 16 weeks in 27%. Time to maximal group increase from baseline was 16 weeks (47 +/- 5 CD4 cell/mm3, p less than 0.001), and time to maximal difference between groups was 16 weeks (45 +/- 7 CD4 cells/mm3, p less than 0.001). These data may be used to illustrate the magnitude, kinetics and variance of surrogate marker and clinical response to ritonavir.

CD4 Lymphocyte Count HIV Infections/*DRUG THERAPY/IMMUNOLOGY HIV Protease Inhibitors/*THERAPEUTIC USE HIV-1/GENETICS/ISOLATION & PURIF Human Lymphocytes Placebos RNA, Viral/BLOOD Thiazoles/*THERAPEUTIC USE Valine/*THERAPEUTIC USE ABSTRACT

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