Phase 2 double-blind, randomized trial of etravirine versus efavirenz in treatment-naive patients: 48-week results.

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.