RIO DE JANEIRO — An investigational protease inhibitor, TMC114, has potent antiviral activity in heavily pretreated HIV-infected patients with primary protease inhibitor mutations, according to results from the POWER-1 study.
The agent plus low-dose ritonavir was effective even in patients harboring three or more primary protease inhibitor (PI) mutations in the 24-week, randomized study (Performance of TMC114/r When Evaluated in Triple-Class-Experienced Patients With PI Resistance), reported Christine Katlama, M.D., of the AIDS clinical research unit at the Hôpital Pitié-Salpêtrière in Paris.
In a poster session at the International AIDS Society Conference on HIV Pathogenesis and Treatment, Dr. Katlama said that overall, the primary end point of 1 log10 or greater viral load reduction from baseline was achieved by 77% of 65 patients taking 600 mg of TMC114 plus 100 mg of ritonavir twice daily, compared with 25% of 63 control patients taking investigator-selected PIs.
A viral load of less than 50 copies/mL was achieved by 53% of the patients on 600 mg of TMC114 plus ritonavir vs. 18% of the control patients
Of the 29 patients with three or more primary PI mutations, 59% of those treated with 600 mg of TMC114 plus ritonavir achieved HIV-1 viral loads below 50 copies/mL vs. 9% of control patients.
There was no excess toxicity in the TMC114 group, Dr. Katlama said. Grade 3 and grade 4 events were observed in 29% of control patients vs. 23% of those treated with 600 mg of TMC114.
For the phase IIb study, 300 patients were randomized to receive one of four doses of TMC114 plus ritonavir, or to receive investigator-selected protease inhibitors. Dr. Katlama presented detailed data only on the most effective regimen of 600 mg of TMC114 plus 100 mg of ritonavir twice daily, which has been chosen for future study.
The patients in this study received an optimal background regimen of nucleoside reverse transcriptase inhibitors, with or without enfuvirtide. They had triple-class experience, had more than one primary PI mutation, were on stable antiretroviral therapy, and had HIV-1 RNA levels greater than 1,000 copies/mL at baseline. TMC114 binds to HIV protease, providing a wide range of durable activity, Dr. Katlama said.
Mark A. Wainberg, Ph.D., director of the McGill University AIDS Centre in Montreal and moderator of the session, said that more than half of the patients on TMC114 achieved viral loads of less than 50 copies/mL. TMC114 “looks to be the next generation PI. It has excellent potency and can make an important difference in experienced patients and probably naive patients as well,” he said.