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10/09/2013

Is Etravirine an Acceptable Alternative to Efavirenz in the Treatment-naive?


Currently, efavirenz (EFV) is the only NNRTI with guidelines-preferred status to serve as the anchor for an initial ART regimen, despite frequent but generally transient central nervous system adverse effects. For many years there has been controversy as to whether long-term EFV exacerbates depression. Recently, an analysis of pooled data from four randomized trials linked efavirenz use with suicidality (for details, see PRN News report “Efavirenz Linked to Suicide Risk at ID Week 2013”). For patients at greatest suicide risk (primarily those with a psychiatric history), alternate anchor drugs should be considered. Nevirapine and rilpivirine are given alternate guidelines status, but neither is ideal due to toxicity, potency or both. Etravirine (ETR) is an NNRTI developed for use in NNRTI-experienced patients because it retains activity against certain common NNRTI resistance mutations. In that patient population, it has a favorable safety and potency profile when dosed at 200 mg twice daily, but was adequately studied or FDA-approved for treatment-naive patients. Floris-Moore et al reported 24 week results of a planned 96 week, single arm, open-label study of ETR 400 mg once daily combined with tenofovir DF and emtricitabine in 80 treatment-naive patients. The median baseline CD4 was 382/mm3 and the HIV RNA 4.52 logs. Twenty patients had baseline HIV RNA >100,000/mL. 86% achieved HIV RNA <50 copies/ mL. The increases in CD4 from baseline was 156/mm3 . There were 5 premature discontinuations, including 2 for rash, 1 missing data and 5 with virologic failure. Only a single case of emergent resistance was documented. Neuropsychiatric adverse effects were reported in only 2 patients. Grade 2 AST/ALT elevations were seen in 5 participants and grade 3/4 in one. This study is small, unblinded, non-comparative, the baseline viral load is fairly low and the reported data is an interim analysis. Nevertheless, the preliminary findings are consistent with a previously published randomized, double-blind, 48 week, phase II study (Sense Trial) comparing once-daily ETR to EFV that demonstrated non-inferior efficacy and low rates of neuropsychiatric adverse events. A large, well powered comparative trial would be needed for definitive proof that ETR-based ART is equivalent to current standard of care, but this trial adds to already suggestive evidence that ETR may be a reasonable alternative to EFV-based ART.

Reference:
Floris-Moore M, Mollan K, Wilkin AM et al. Antiretroviral Activity and Safety of Once-daily Etravirine in Treatment-naıve HIV-infected Adults. ID Week 2013, San Francisco, CA, October 2-6, 2013, abstract 170.


Source: Reporting from San Francisco for PRN News: David H Shepp, MD