Pharmacokinetic and Pharmacodynamic Comparison of Once-Daily Efavirenz (400 mg vs. 600 mg) in Treatment-Naive HIV-Infected Patients: Results of the ENCORE1 Study

Dickinson, L
Amin, J
Else, L
Boffito, M
Egan, D
Owen, A
Khoo, S
Back, D
Orrell, C
Clarke, A
Losso, M
Phanuphak, P
Carey, D
Cooper, DA
Emery, S
Puls, R

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Publication date

October 2015

DOI

10.1002/cpt.156

Publisher

Wiley

Abstract

Daily efavirenz 400 mg (EFV400) was virologically noninferior to 600 mg (EFV600) at 48 weeks in treatment €naïve patients. We evaluated EFV400 and EFV600 pharmacokinetics (NONMEM v. 7.2), assessing patient demographics and genetic polymorphisms (CYP2B6, CYP2A6, CYP3A4, NR1I3) as covariates and explored relationships with efficacy (plasma HIV € RNA (pVL) T/983T>C/CYP2A6∗9B/∗17 and weight were associated with efavirenz CL/F. Exposure was significantly lower for EFV400 (geometric mean ratio, GMR; 90% confidence interval, CI: 0.73 (0.68-0.78)) but 97% (EFV400) and 98% (EFV600) of evaluable pVL was <200 copies/mL at 48 weeks (P = 0.802). Four of 20 patients with mid € dose concentrations <1.0 mg/L had pVL ≥200 copies/mL (EFV400 = 1; EFV600 = 3)....