The NNRTI etravirine is approved for twice-daily dosing in both treatment-naive and treatment-experienced patients. The pharmacokinetic characteristics of etravirine suggest it may be given once daily, and several recent trials have examined the efficacy of QD etravirine. In particular, the SENSE trial randomized 157 treatment-naive individuals to either etravirine (400 mg QD) or efavirenz, in combination with 2 NRTIs selected by the investigator (60% received tenofovir/emtricitabine). The median baseline HIV RNA level was 4.8 log10 copies/mL and the level was >100,000 copies/mL in 23% of subjects. At screening, no resistance to study ARVs was detected, though NNRTI or NRTI mutations were found in 16% of etravirine recipients and in 5% of efavirenz recipients on testing conducted at baseline.
At 48 weeks, the HIV RNA level was <50 copies/mL in 75.9% of the etravirine group and in 74.4% of the efavirenz group, by TLOVR analysis. Results appeared to be similar for subjects with pretreatment HIV RNA levels of >100,000 copies/mL. Increases in CD4 counts were approximately 234 cells/µL in each arm. The study was not powered to evaluate noninferiority. Among the 11 subjects who experienced virologic failure, 4 were etravirine recipients. None of those in the etravirine group had emergent resistance mutations, whereas 3 of 7 who experienced virologic failure on efavirenz developed NRTI or NNRTI mutations. Virologic failure was not associated with the mutations observed at baseline.
Neuropsychiatric adverse effects were substantially more common in the efavirenz arm, both in the early weeks of the study and throughout the follow-up phase (21.5% vs 6.3%, respectively, at 48 weeks), and lipid elevations also were more common in the efavirenz group (grade 3-4 LDL elevations were seen in 10% vs 3%, respectively, of subjects); rates of rash were the same in the 2 groups.
| Clinical Bottom Line|
This study suggests that once-daily etravirine is effective and well tolerated in initial therapy. Although it is not currently approved for once-daily dosing, etravirine may be a reasonable treatment option for select individuals, particularly those for whom other NNRTIs may not be appropriate. Additional evaluations of once-daily etravirine are under way.
Gazzard B, Duvivier C, Zagler C, et al. Phase 2 double-blind, randomized trial of etravirine versus efavirenz in treatment-naive patients: 48 week results. AIDS. 2011 Nov 28;25(18):2249-58.