Efficacy and safety of lersivirine versus etravirine for the treatment of HIV-1 infection in patients with prior non-nucleoside reverse transcriptase inhibitor (NNRTI) use and evidence of NNRTI resistance: A randomized phase 2B trial

Objective: To assess the efficacy and safety of lersivirine versus etravirine in patients with HIV-1 and prior non-nucleoside reverse transcriptase inhibitor (NNRTI) use and evidence of NNRTI resistance. Methods: In this 96-week, phase 2b study, 97 patients were randomized and treated with lersivirine 750 mg qd (n = 31), lersivirine 1,000 mg qd (n = 32), and etravirine 200 mg bid (n = 34), plus one optimized nucleoside reverse transcriptase inhibitor and darunavir/ritonavir 600/100 mg bid. The primary endpoint was the percentage of patients with HIV-1 RNA <50 copies/mL at week 24. Results: At week 24, HIV-1 RNA <50 copies/mL was achieved by fewer patients receiving lersivirine 750 mg (48.4%) and 1,000 mg (43.8%) qd compared with etravirine 200 mg qd (67.7%) (intention to treat [ITT], missing/switch/discontinuation equals failure [MSDF]). At week 48, HIV-1 RNA <50 copies/mL and <400 copies/mL were also achieved by fewer patients receiving lersivirine 750 mg (41.9% and 41.9%, respectively) and 1,000 mg (31.3% and 34.4%, respectively) qd compared with etravirine 200 mg bid (61.8% and 70.6%, respectively) (ITT, MSDF). Least squares means (SE) change from baseline in log10 transformed HIV-1 RNA at week 48 was -1.42 (0.27) and -0.95 (0.28) copies/mL for lersivirine 750 mg and 1,000 mg qd, respectively, versus -2.02 (0.26) copies/mL for etravirine 200 mg bid (ITT). Lersivirine and etravirine were generally safe and well-tolerated. Conclusions: Lersivirine 750 mg and 1,000 mg qd was associated with lower rates of viral suppression at week 24 and week 48 versus etravirine in patients with prior NNRTI use and evidence of NNRTI resistance. No new safety signals were detected.