ICAAC: TMC114 shows further promise in second POWER study

The POWER-2 study, a US study of new protease inhibitor TMC114 in triple-class-experienced patients, has confirmed that TMC114 boosted by ritonavir is superior to other boosted protease inhibitors over 24 weeks of follow-up. The findings were presented last month at the 45^th Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington DC.

The study also provided further information on the factors that predict a successful response to TMC114, the protease inhibitor widely seen as the most potent salvage agent on the horizon. Use alongside enfuvirtide (T-20) and/or a lower number of primary protease mutations (indicative of less extensive resistance) significantly improved an individual’s chances of achieving a viral load below 50 copies/ml by week 24.

POWER-2 was a phase IIb randomised study that compared four different doses of TMMC114/ritonavir plus background therapy optimised by resistance testing, with a control arm in which participants received an investigator-selected protease inhibitor plus optimised background regimen.

The study recruited individuals with prior exposure to nucleoside analogues, non-nucleoside reverse transcriptase inhibitors and protease inhibitors who were currently taking a protease inhibitor-based regimen but who had detectable viral load above 1000 copies/ml.

Two hundred and twenty-five participants received TMC114/ritonavir and 53 received a control regimen.

The participants recruited to this study were highly treatment-experienced, with an average exposure to eleven prior antiretroviral agents including four protease inhibitors. Participants had an average of three primary protease mutations and high-level resistance to lopinavir (median fold reduction in phenotypic sensitivity to lopinavir was 78 in the TMC114 group and 83 in the control group).

The efficacy analysis presented at the 45th ICAAC concentrated on results in the control arm and the arm that received TMC114/ritonavir at a dose of 600/100mg twice daily (the dose now selected to go forward into phase III studies). The proportion of patients who achieved viral load below 50 copies at week 24 was significantly higher in the twice daily treatment groups (400mg/100mg bid 36%, 600/100mg bid 39%) than in the once daily groups.

When analysed by baseline characteristics, enfuvirtide in the background regimen of enfuvirtide-naïve patients resulted in a substantial improvement in performance of TMC114. Sixty-four per cent of the TMC114 600/100mg group who received enfuvirtide achieved viral load below 50 copies/ml at week 24, compared to 7% of the comparato PI group. Amongst those TMC114 recipients who did not include enfuvirtide in the background regimen, the proportion who achieved viral load below 50 copies was 30% (compared to 4%) in the comparator PI group.

Adverse events appeared to be less frequent in the TMC114 arm when follow-up data was adjusted for drug exposure (138 patient years of drug exposure were recorded in the TMC arm, compared to 21 patient years in the comparator PI group), although more grade 3 and 4 adverse events were recorded in the TMC114 arm (28% vs 19%).