Ruxrungtham K., Pedro R.J., Latiff G.H., Conradie F., Domingo P., Lupo S., Pumpradit W., Vingerhoets J.H., Peeters M., Peeters I., Kakuda T.N., De Smedt G., Woodfall B.
HIV-NAT, Thai Red Cross AIDS Research Center, Chulalongkorn University, 104 Rajdumri Road, Pathumwan, Bangkok 10330, Thailand; Universidad de Campinas, Sao Paulo, Brazil; Maxwell Centre, Durban, South Africa; University of Witwatersrand, Johannesburg, South Africa; Autonomous University of Barcelona, Barcelona, Spain; Instituto CAICI, Rosario, Argentina; HIV-NAT, Thai Red Cross AIDS Research Center, 104 Rajdumri Road, Pathumwan, Bangkok 10330, Thailand; Tibotec BVBA, Mechelen, Belgium; Tibotec Inc., Yardley, PA, United States
Ruxrungtham, K., HIV-NAT, Thai Red Cross AIDS Research Center, Chulalongkorn University, 104 Rajdumri Road, Pathumwan, Bangkok 10330, Thailand; Pedro, R.J., Universidad de Campinas, Sao Paulo, Brazil; Latiff, G.H., Maxwell Centre, Durban, South Africa; Conradie, F., University of Witwatersrand, Johannesburg, South Africa; Domingo, P., Autonomous University of Barcelona, Barcelona, Spain; Lupo, S., Instituto CAICI, Rosario, Argentina; Pumpradit, W., HIV-NAT, Thai Red Cross AIDS Research Center, 104 Rajdumri Road, Pathumwan, Bangkok 10330, Thailand; Vingerhoets, J.H., HIV-NAT, Thai Red Cross AIDS Research Center, 104 Rajdumri Road, Pathumwan, Bangkok 10330, Thailand; Peeters, M., Tibotec BVBA, Mechelen, Belgium; Peeters, I., Tibotec BVBA, Mechelen, Belgium; Kakuda, T.N., Tibotec Inc., Yardley, PA, United States; De Smedt, G., Tibotec BVBA, Mechelen, Belgium; Woodfall, B., Tibotec BVBA, Mechelen, Belgium
Objectives: TMC125-C227, an exploratory phase II, randomized, controlled, open-label trial, compared the efficacy and safety of TMC125 (etravirine) with an investigator-selected protease inhibitor (PI) in nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant, protease inhibitor-naïve, HIV-1-infected patients. Methods: Patients were randomized to TMC125 800 mg twice a day (bid) (phase II formulation; n = 59) or the control PI (n = 57), plus two nucleoside reverse transcriptase inhibitors (NRTIs). Results: In an unplanned interim analysis, patients receiving TMC125 demonstrated suboptimal virological responses relative to the control PI. Therefore, trial enrolment was stopped prematurely and TMC125 treatment discontinued after a median of 14.3 weeks. In this first-line NNRTI-failure population, baseline NRTI and NNRTI resistance was high and reduced virological responses were observed relative to the control PI. No statistically significant relationship was observed between TMC125 exposure and virological response at week 12. TMC125 was better tolerated than a boosted PI for gastrointestinal-, lipid- and liver-related events. Conclusions: In a PI-naïve population, with baseline NRTI and NNRTI resistance and NRTI recycling, TMC125 was not as effective as first use of a PI. Therefore the use of TMC125 plus NRTIs alone may not be optimal in PI-naïve patients with first-line virological failure on an NNRTI-based regimen. Baseline two-class resistance, rather than pharmacokinetics or other factors, was the most likely reason for suboptimal responses. © 2008 British HIV Association.