Efficacy and safety of darunavir-ritonovir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials.
Clotet C, Bellos N, Molina J et al. Lancet, 2007, 369, 1169-1178. Review by Derek J Chan Division of Sexual Health, Prince of Wales Hospital, Sydney, Australia
The randomised multinational, phase IIb studies POWER 1 and 2 compared the virological efficacy of several dosages of darunavir-ritonovir (DRV/RTV) plus optimised background therapy (OBT) with control protease inhibitors (PIs) plus OBT. By week 48, 58% of patients in POWER 1 and 39% in POWER 2 taking DRV/RTV 600/100mg twice daily attained viral load <50 copies/ml compared to 18% and 7%, respectively, taking other PIs. The studies were deemed similar enough in design to combine the efficacy and safety data for the DRV/RTV 600/ 100mg twice daily dose against control PIs in the current study. It was found that 64% of DRV/RTV subjects and 61% of control PI subjects were resistant to all PIs (excluding tipranavir, which was apparently unavailable during this study).
The overall discontinuation rate was higher in the control PI arm compared to the DRV/RTV arm and was mainly attributable to virological failure. None the less, the rate of discontinuation did not affect the efficacy analyses of either arm: the difference between treatments was already well established by week 12 and 100 subjects (76%) in the DRV/RTV arm and 29 (23%) in the control PI arm attained a viral load decrease of at least 1 [log.sub.10] copies/ml compared to baseline (difference 53%, 95% CI 42-63%, P<0.0001).
Grade 3 or 4 adverse events (hyperlipidaemia and increased pancreatic lipase) were commoner in the DRV/RTV arm compared to the control arm; however, there was greater use of lipid-lowering agents in the control arm. Episodes of genital herpes were more common in the DRV/RTV group and were thought to be related to immune reconstitution of herpes simplex virus. Overall, this intent-to-treat analysis found that 67/110 (61%) of patients randomised to receive DRV/RTV 600/100mg BD attained viral load drop of at least 1 [log.sub.10] copies/mIL cf. 18/120 (15%) of control PI subjects. Although the study was small and consisted of predominantly caucasian males, the proportional differences in efficacy observed in this study support the use of DRV/RTV as a potent alternative in treatment-experienced patients with multiple protease resistance mutations.
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|Author:||Chan, Derek J.|
|Publication:||Journal of HIV Therapy|
|Date:||Jun 1, 2007|
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