Nevirapine pharmacokinetics when initiated at 200 mg or 400 mg daily in HIV-1 and tuberculosis co-infected Ugandan adults on rifampicin

Background: Rifampicin lowers nevirapine plasma concentrations by inducing cytochrome P450. However, few data are available on this interaction during the lead-in period of nevirapine treatment. Methods: Eighteen HIV-1/tuberculosis co-infected adults receiving rifampicin daily as part of anti-tuberculosis therapy were evenly randomized to nevirapine initiation by dose escalation (NVP200) or nevirapine initiation at 200 mg twice daily (NVP400). Subjects underwent 12 h intensive pharmacokinetic sampling on Days 7, 14 and 21 of nevirapine treatment. A minimum effective concentration (MEC) of 3000 ng/mLwas used to interpret nevirapine concentrations 12 h after dosing (C12). Trial registration number: NCT00617643 (www.clinicaltrials.gov). Results: Day 7 geometric mean nevirapine C12 [90% confidence interval (CI)] was 1504 (1127-2115) ng/mL and 3148 (2451-4687) ng/mL in the NVP200 and NVP400 arms, respectively (P,0.01). Nevirapine C12 on Days 14 and 21 was similar. On Day 21, nevirapine concentration in 64% of patients was below the MEC. On Day 7, geometric mean area under the curve (AUC0-12) was lower in the NVP200 arm, 25223 (90% CI, 21978-29695) ng.h/mLversus 43195 (35607-57035) ng.h/mL in the NVP400 arm (P,0.01). Similarly, on Day 14, nevirapine AUC0-12 was lower in the NVP200 arm 23668 (18253-32218) ng·h/mL versus the NVP400 arm 44918 (36264-62769) ng.h/mL (P=0.03). Conclusions: In co-treated patients, nevirapine concentrations were below the MEC during initiation with dose escalation. Nevirapine initiation at the maintenance dose of 200 mg twice daily is preferred. Sub-therapeutic nevirapine concentrations were common at Day 21 with either regimen. Evaluation of higher nevirapine maintenance doses may be considered. © The Author 2010. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.