Impact of the background regimen on virologic response to etravirine: pooled 48-week analysis of DUET-1 and -2.

PURPOSE: This subgroup analysis of the phase 3 DUET trials examined the impact of the background regimen on virologic response to etravirine in treatment-experienced patients. METHODS: Patients received etravirine 200 mg or placebo, both twice daily with a background regimen of darunavir/ritonavir, investigator-selected nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), and optional enfuvirtide. Virologic response at week 48 (viral load <50 HIV-1 RNA copies/mL) was analyzed by the number and activity of background agents. RESULTS: Baseline phenotypic sensitivity score (PSS), enfuvirtide use, darunavir fold change in 50% effective concentration (FC), and number of baseline darunavir resistance-associated mutations (RAMs) were significant predictors of response to etravirine (P < .0001, P = .0018, P < .0001, and P = .0120, respectively). The number of active NRTIs was not a significant predictor of response (P = .0626). The highest response rates in etravirine-treated patients were associated with PSS ≥2, de novo enfuvirtide use, darunavir FC ≤10, ≤1 darunavir RAM, and ≥2 active NRTIs. Virologic response was consistently higher in etravirine-treated patients than placebo-treated patients, regardless of the activity of the background regimen. Response rates according to baseline PSS were 46% to 79% in the etravirine group versus 6% to 75% in the placebo group. CONCLUSION: The results of this subanalysis demonstrate higher virologic response rates with increased activity of the background regimen in both treatment groups, with the highest responses achieved in patients using ≥2 active agents in addition to etravirine.

Single- and multiple-dose pharmacokinetics of etravirine administered as two different formulations in HIV-1-infected patients.

BACKGROUND: An open-label, randomized, crossover study to evaluate the pharmacokinetics of two different formulations of etravirine after single and multiple dosing. METHODS: Treatment-experienced HIV-1-infected patients with viral load <50 copies/ml continued their current antiretroviral regimen and added etravirine twice daily for 7 days with a morning intake on day 8. Etravirine was administered following food as either 800 mg twice daily of the Phase II formulation or 100 mg or 200 mg twice daily of the Phase III formulation. A 12 h pharmacokinetic assessment was performed on days 1 and 8. RESULTS: After single- and multiple-dose administration, the exposure to etravirine was lower with 100 mg twice daily and higher with 200 mg twice daily compared with 800 mg twice daily. On day 8, the mean (+/-SD) area under the plasma concentration-time curve over 12 h (AUC0-12 h) was 1,284 (+/-958) ng x h/ml when etravirine was administered as 100 mg twice daily (n=33), 3,713 (+/-2,069) ng x h/ml when administered as 200 mg twice daily (n=27) and 2,607 (+/-2,135) ng x h/ml when administered as 800 mg twice daily (n=32). Both formulations and all doses of etravirine tested were generally safe and well tolerated. CONCLUSIONS: The range of exposure to etravirine was comparable between 200 mg twice daily dose and 800 mg twice daily. The Phase III formulation of etravirine significantly improves the bioavailability of etravirine over the Phase II formulation with reduced interpatient variability in etravirine pharmacokinetics.