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


METHODS
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/microL and HIV RNA 4.6 log(10) HIV-1 RNA copies/mL), CD4 counts rose by a mean of 98 cells/microL for TMC114/r 600/100 mg twice a day (bid) vs. 17 cells/microL for CPI at week 24; HIV RNA fell by a median of 1.90 and 0.49 log(10) 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.
Hill
A
A
Department of Pharmacology, University of Liverpool, Liverpool, UK. microhaart@aol.com
Montaner
J
J
Smith
C
C
D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D000069454:Darunavir; D003627:Data Interpretation, Statistical; D018450:Disease Progression; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*
D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D013449:Sulfonamides; D019438:Ritonavir; D000069454:Darunavir