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

M Lamorde, P Byakika-Kibwika, V Okaba-Kayom, M Ryan, P Coakley, M Boffito, R Namakula, F Kalemeera, R Colebunders, D Back, S Khoo, C Merry

    Research output: Contribution to journalA1: Web of Science-articlepeer-review


    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/mL was used to interpret nevirapine concentrations 12 h after dosing (C(12)). Trial registration number: NCT00617643 ( Results Day 7 geometric mean nevirapine C(12) [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 C(12) 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 (AUC(0-12)) was lower in the NVP200 arm, 25 223 (90% CI, 21 978-29 695) ng.h/mL versus 43 195 (35 607-57 035) ng.h/mL in the NVP400 arm (P < 0.01). Similarly, on Day 14, nevirapine AUC(0-12) was lower in the NVP200 arm 23 668 (18 253-32 218) ng.h/mL versus the NVP400 arm 44 918 (36 264-62 769) 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.
    Original languageEnglish
    JournalJournal of Antimicrobial Chemotherapy
    Issue number1
    Pages (from-to)180-183
    Number of pages4
    Publication statusPublished - 2011


    • B780-tropical-medicine
    • Viral diseases
    • HIV-1
    • AIDS
    • Co-infections
    • Bacterial diseases
    • Tuberculosis
    • Mycobacterium tuberculosis
    • HAART
    • Antiretrovirals
    • Nevirapine
    • Pharmacokinetics
    • Rifampicin
    • Dosage
    • Toxicity
    • Clinical trials
    • Uganda
    • Africa-East


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