IAS: TMC114 plus low-dose ritonavir effective and well-tolerated in 3-class-experienced HIV patients

Mindy Tanzola

In triple-class-experienced HIV patients, the investigational protease inhibitor, TMC114, appears effective and well- tolerated when administered with low-dose ritonavir (Norvir) and an optimised background regimen, according to a phase II trial presented at the Third International AIDS Society Conference on HIV Pathogenesis and Treatment in Rio de Janeiro, Brazil.

TMC114 binds precisely to HIV protease, giving it a wide range of durable in vitro activity, even against PI-resistant strains. The POWER 1 study (Performance Of TMC114/r When Evaluated in triple-class-experienced patients with PI Resistance), investigated the efficacy and safety of 24 weeks of various doses of TMC114 plus low-dose ritonavir compared with investigator-selected PIs. A combined planned interim 24-week analysis from this and a companion study, POWER 2, were previously presented at the 12th Conference on Retroviruses and Opportunistic Infections in February 2005.

The multicenter international study enrolled 318 individuals with triple-class-experience, on stable antiretroviral therapy and with HIV-1 RNA levels above 1000 copies/ml. Patients were randomised to receive either a control PI (n = 63) or one of the following TMC114/ritonavir regimens: 400/100 mg (n = 64) once daily, 800/100 mg (n = 63) once daily, 400/100 mg (n = 63) twice daily, or 600/100 mg (n = 65) twice daily. All patients received an optimised background regimen.

In the efficacy portion of the study, Christine Katlama and colleagues, at Hôpital Pitié-Salpêtrière in Paris, France, evaluated changes in HIV-1 RNA levels and CD4 cell counts at Week 24. They found TMC114/ritonavir to be significantly more effective in reducing viral load compared with comparator PIs (p 10 decrease in HIV-1 viral load versus 25% of control-treated patients.

Furthermore, TMC114/ritonavir was effective in patients with three or more primary PI mutations. Of 29 such patients treated with the highest dose of TMC114/ritonavir, 59% achieved HIV-1 viral loads below 50 copies/ml versus 9% of control-treated patients.

According to a Week 24 safety analysis carried out by Beatriz Grinsztejn, and colleagues, of the Hospital Evandro Chagas in Rio de Janeiro, Brazil, TMC114/ritonavir was well tolerated. Adverse events were mostly mild to moderate, and serious adverse events were similar between treatment groups. Grade 3/4 events were observed in 29% of control-treated patients versus 23% of those treated with the highest TMC114 dose. The incidence of adverse events was not affected by TMC114 dose.

Discontinuation rates differed significantly between treatment arms (10% for TMC114/ritonavir versus 62% for control PIs, although discontinuations resulting from adverse events were similar between groups (5% versus 6%, respectively). This resulted in a significant difference in mean drug exposure (40 versus 26 weeks, respectively).

After adjusting for total drug exposure by calculating incidence per 100 patient-years, common adverse events were less prevalent among patients receiving 600/100 mg TMC114/ritonavir than control PIs and included diarrhoea (18% in TMC114/ritonavir versus 67% in control), nausea (14% versus 25%, respectively), and headache (18% versus 47%, respectively).

In her presentation, Dr. Katlama expressed her enthusiasm that TMC114 appears well tolerated and effecti

ve even in patients with multiple PI resistance mutations.

This content was licensed to aidsmap by iMedOptions, publishers of http://clinicaloptions.com. Copyright iMedOptions, LLC, 2005

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