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.
Hill
A
A
Department of Pharmacology, University of Liverpool, Liverpool, UK. microhaart@aol.com
Moyle
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G
D000328:Adult; D000069454:Darunavir; D004359:Drug Therapy, Combination; D005260:Female; D006678:HIV / Q000235:genetics / Q000254:growth & development*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011725:Pyridines / Q000627:therapeutic use*; D011753:Pyrones / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*
D017320:HIV Protease Inhibitors; D011725:Pyridines; D011753:Pyrones; D012367:RNA, Viral; D013449:Sulfonamides; D019438:Ritonavir; D000069454:Darunavir; C107201:tipranavir