Relative antiviral efficacy of ritonavir-boosted darunavir and ritonavir-boosted tipranavir vs. control protease inhibitor in the POWER and RESIST trials.

OBJECTIVE:

To compare the relative antiviral efficacy of TMC114 with low-dose ritonavir (TMC114/r) and tipranavir with low-dose ritonavir (TPV/r) vs. control protease inhibitor (CPI) in treatment-experienced patients, using data from the POWER 1/2 and RESIST 1/2 trials. These trials recruited antiretroviral-experienced patients with HIV RNA > 1000 HIV-1 RNA copies/mL and at least one primary PI mutation, and used optimized nucleoside reverse transcriptase inhibitors with or without enfuvirtide, plus investigator-selected CPI in the control arms.

METHODS:

For the POWER trials, data from the 600/100 mg twice a day (bid) dose and CPI arms (n=201) were included, while all data from the RESIST trials (TPV/r 500/200 mg bid and CPI; n=1159) were included. The difference in week 24 efficacy (intent to treat) for the new PI vs. CPI was compared between the trials.

RESULTS:

Overall baseline characteristics were well matched across the trials. At week 24, 72% of TMC114/r patients achieved a > or =1 log(10) copies/mL reduction in HIV RNA compared with 40% of TPV/r patients (for CPI patients, this percentage was 21 and 18%, respectively, in the POWER and RESIST trials). The treatment benefit of TMC114/r over CPI in the POWER trials was greater (outside the 95% confidence intervals) than the benefit of TPV/r over CPI in the RESIST trials, for the 24-week HIV RNA endpoints of 1 log(10) copies/mL reduction, <400 copies/mL and <50 copies/mL, and also for the mean rise in CD4 count. In sensitivity analysis, this difference in efficacy was strongest for those who did not also use enfuvirtide.

CONCLUSIONS:

Given the caveats of this type of analysis (for example, possible differences in trial conduct, and undetected differences in baseline resistance profiles), the efficacy benefits of TMC114/r vs. CPI in the POWER trials appear to be greater than the benefits of TPV/r vs. CPI in the RESIST trials, for patients who did not also use enfuvirtide.