Prediction of clinical benefits of ritonavir-boosted TMC114 from treatment effects on CD4 counts and HIV RNA

Abstract

Objective: The aim of the study was to predict reductions in progression to AIDS/death associated with the treatment benefit of antiretrovirals on CD4 counts and HIV RNA in the era of highly active antiretroviral therapy (HAART). Design: The study design was a pooled analysis of two trials (POWER 1 and POWER 2) of optimized background treatment plus either TMC114/ritonavir (TMC114/r) or control protease inhibitor (CPI). Methods: Across the two randomized trials (mean baseline CD4 count 114 cells/μL and HIV RNA 4.6 log10 HIV-1 RNA copies/mL), CD4 counts rose by a mean of 98 cells/μL for TMC114/r 600/100 mg twice a day (bid) vs. 17 cells/μL for CPI at week 24; HIV RNA fell by a median of 1.90 and 0.49 log10 copies/mL in the two groups, respectively. For the CD4 categorization method, cohort data on rates of progression to AIDS/death during HAART within preset CD4 ranges were used to predict rates of progression during TMC114/r and CPI treatment. For the regression method, data from clinical endpoint trials were used to correlate historical treatment effects on HIV RNA and CD4 with clinical benefits. Results: The CD4 categorization method predicted a 48% reduction in clinical progression to AIDS/death for TMC114/r vs. CPI. The regression method predicted a 55% reduction [95% confidence interval (CI) 45-66%] in the hazard of progression to AIDS/death based on CD4 counts, with a 47% reduction (95% CI 38-53%) predicted from effects on HIV RNA. Conclusions: Independent methods generated similar predictions of a 47-55% reduction in progression to AIDS/death for TMC114/r vs. CPI treatment, based on the changes in CD4 counts and HIV RNA from the POWER 1 and POWER 2 trials. These methods could be used to estimate clinical benefits of other antiretrovirals. © 2007 British HIV Association.