Phase 2 double-blind, randomized trial of etravirine versus efavirenz in treatment-naive patients

BACKGROUND: The Study of Etravirine Neuropsychiatric Symptoms versus Efavirenz (SENSE) trial compared etravirine with efavirenz in treatment-naive patients. The primary endpoint was neuropsychiatric adverse events up to week 12; HIV RNA suppression at week 48 was a secondary endpoint. METHODS: Patients with HIV RNA more than 5000 copies/ml were randomized to etravirine 400 mg once daily (n = 79) or efavirenz (n = 78), plus two nucleoside analogues. HIV RNA less than 50 copies/ml at week 48 was analysed using the time to loss of virological response (TLOVR) algorithm. Drug resistance at treatment failure and safety endpoints were also evaluated. RESULTS: At baseline, the median CD4 cell count was 302 cells/μl and HIV RNA was 4.8 log10 copies/ml. In the intent to treat TLOVR analysis at week 48, 60 of 79 (76%) patients on etravirine versus 58 of 78 (74%) on efavirenz had HIV RNA less than 50 copies/ml. In the on-treatment analysis, 60 of 65 (92%) taking etravirine had HIV RNA les than 50 copies/ml versus 58 of 65 (89%) for efavirenz: etravirine showed noninferior efficacy versus efavirenz in both analyses (P < 0.05). Four patients had virological failure in the etravirine arm: none developed resistance to nucleoside analogues or nonnucleosides. Seven patients had virological failure in the efavirenz arm: three developed treatment-emergent resistance to nucleoside analogues and/or nonnucleosides. At the week 48 visit, the percentage with ongoing neuropsychiatric adverse events was 6.3% for etravirine and 21.5% for efavirenz (P = 0.011). CONCLUSION: First-line treatment with etravirine 400 mg once daily and two nucleoside reverse transcriptase inhibitors (NRTIs) led to similar rates of HIV RNA suppression, compared with efavirenz and two NRTIs. None of the patients with virological failure in the etravirine arm developed resistance to nonnucleosides.