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Etravirine Matches Efavirenz Effectiveness with Fewer Side Effects

The next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) etravirine (Intelence) worked as well as the widely-used NNRTI efavirenz (Sustiva, also in the Atripla combination pill) but with fewer central nervous system side effects, researchers reported in the August 30, 2011, advance online edition of AIDS.

Brian Gazzard and fellow investigators with the SENSE trial compared etravirine versus efavirenz regimens as first-line therapy, focusing on neuropsychiatric adverse events such as dizziness, anxiety, or abnormal dreams during the first 12 weeks of treatment. Results from the primary week 12 analysis were presented at the XVIII International AIDS Conference (AIDS 2010) in Vienna, showing that etravirine recipients were significantly less likely to experience such side effects. Follow-up continued to assess virological response through week 48.

A total of 157 treatment-naive participants with HIV RNA > 5000 copies/mL and no known drug-resistance mutations at baseline were randomly assigned to receive 400 mg once-daily etravirine or 600 mg once-daily efavirenz, both in combination with 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), either tenofovir/emtricitabine (Truvada), abacavir/lamivudine (Epzicom), or zidovudine/lamivudine (Combivir). About 80% were men, 85% were white, the median age was 36 years, and the baseline CD4 cell count was 302 cells/mm³.

Results

• In an intent-to-treat time to loss of virological response (TLOVR) analysis at 48 weeks, the drugs worked equally well, with 76% of etravirine recipient and 74% of efavirenz recipients maintaining HIV RNA < 50 copies/mL.
• In an on-treatment analysis, the corresponding response rates were 92% and 89%, respectively.
• Etravirine demonstrated non-inferior efficacy compared with efavirenz in both analyses.
• 4 participants experienced virological failure in the etravirine arm, but none of them developed resistance to NRTIs or NNRTIs.
• 7 patients experienced virological failure in the efavirenz arm, of whom 3 developed treatment-emergent resistance to NRTIs or NNRTIs.
• At week 48, significantly fewer etravirine recipients than efavirenz recipients reported ongoing neuropsychiatric adverse events, 6.3% vs 21.5%, respectively.

Based on these findings, the study authors concluded, "First-line treatment with etravirine 400 mg [once daily] + 2 NRTIs led to similar rates of HIV RNA suppression, compared with efavirenz + 2 NRTIs."

"None of the patients with virological failure in the etravirine arm developed resistance to NRTIs or NNRTIs," they added.

Investigator affiliations: Lluita Contra la SIDA Foundation, University Hospital Germans Trias i Pujol, Badalona; Hospital Universitario La Paz, Madrid; Hospital Sant Pau, Barcelona; Hospital Clinic, IDIBAPS, Barcelona; Hospital Universitario de Valme, Sevilla; Hospital Reina Sofia, Cordoba; Hospital Ramon y Cajal, Madrid, Spain.

9/2/11

Reference

B Gazzard, C Duvivier, C Zagler, et al. Phase 2 double-blind, randomised trial of etravirine versus efavirenz in treatment-naive patients: 48 week results. AIDS (abstract). August 30, 2011 (Epub ahead of print).