Pharmacokinetics of nevirapine in HIV-infected children under 3 years on rifampicin-based antituberculosis treatment.

Journal article

OBJECTIVE: There is an urgent need to optimize cotreatment for children with tuberculosis and HIV infection. We described nevirapine pharmacokinetics in Zambian children aged less than 3 years, cotreated with nevirapine, lamivudine and stavudine in fixed-dose combination (using WHO weight bands) and rifampicin-based antituberculosis treatment. DESIGN: Twenty-two children received antituberculosis and antiretroviral therapy (ART) concurrently for 4 weeks before pharmacokinetic sampling. Plasma nevirapine concentrations were determined in samples taken immediately before, and 1, 2 and 6 h after an observed dose. Nevirapine pharmacokinetics were compared with those in 16 children aged less than 3 years without tuberculosis. RESULTS: Twenty-two children were treated for HIV/TB coinfection, 10 of whom were girls. One boy was excluded from analysis for nonadherence. The median age was 1.6 years (range: 0.7-3.2). Median weight was 8.0 kg (range: 5.1-10.5). The baseline CD4% was 13.1 (range: 3.9-43.6). Median predose concentration of nevirapine was 2.93 mg/l (range: 1.06-11.4), and peak concentration was 6.33 mg/l (range: 2.61-14.5). The nevirapine AUC up to 12 h was estimated as 52.0 mg.h/l (range: 22.6-159.7) compared with 90.9 mg.h/l (range: 40.4-232.1) in children without tuberculosis (P < 0.001). Predose concentrations of nevirapine were less than 3.0 mg/l in 11 children on tuberculosis treatment versus none of the 16 children without tuberculosis treatment (P = 0.001). AUC was 41% (95% CI: 23-54%) lower in children with tuberculosis than without tuberculosis (P < 0.001) after adjusting for dose per square meter. CONCLUSION: : We found substantial reductions in nevirapine concentrations in young children receiving rifampicin. Further studies are needed to define the pharmacokinetics, safety and efficacy of adjusted doses of nevirapine-based ART in young children with tuberculosis.

Authors: Oudijk, J; McIlleron, H; Mulenga, V; Chintu, C; Merry, C

• Publication status: Published
• Journal: AIDS (London, England)
• Volume: 26
• Issue: 12
• Pages: 1523-1528
• Publication date: 2012-07-01
• DOI: 10.1097/qad.0b013e3283550e20
• EISSN: 1473-5571
• ISSN: 0269-9370
• Language: English
• Keywords: Infant; Case-Control Studies; Child, Preschool; Female; HIV Infections; Coinfection; Anti-HIV Agents; Tuberculosis; Humans; Stavudine; Lamivudine; Rifampin; Antibiotics, Antitubercular; Treatment Outcome; Zambia; Nevirapine; Male