Pharmacokinetics of nevirapine in HIV-infected infants weighing 3 kg to less than 6 kg taking paediatric fixed dose combination tablets.

Journal article

OBJECTIVES: To evaluate pharmacokinetics of nevirapine, lamivudine and stavudine in HIV-infected Zambian infants receiving fixed dose combination (FDC) antiretroviral tablets (Triomune Baby). DESIGN: Phase I/II study. METHODS: Sixteen HIV-infected children at least 1 month, weighing 3 kg to less than 6 kg were enrolled. Blood was sampled at t = 0, 2, 6 and 12 h after observed intake of one FDC tablet (50 mg nevirapine, 6 mg stavudine, 30 mg lamivudine) 4 weeks after starting treatment. Safety and viral load response over 48 weeks were determined. RESULTS: The median [interquartile range (IQR)] age, body weight and daily nevirapine dose in 15 included children (eight girls) were 4.8 (4.2, 8.4) months, 5.3 (4.3, 5.5) kg and 348 (326 385) mg/m, respectively. The median (IQR) nevirapine area under the concentration-time curve (AUC0-12 h), Cmax and C12 h were 70 (56, 104) h mg/l, 7.5 (6.2, 10) mg/l, and 4.3 (2.9, 6.9) mg/l, respectively. Values were on average higher than reported in adults, but approximately 20% lower than previously reported in children weighing at least 6 kg. Four of 15 (27%) children had a subtherapeutic nevirapine C12 h (defined as <3.0 mg/l) compared to only three of 63 (5%) children weighing at least 6 kg (P = 0.02), whereas children aged less than 5 months [three of six (50%)] may have the highest risk for subtherapeutic nevirapine C12 h (P = 0.24). No association was found between viral load values and nevirapine plasma pharmacokinetic parameters (P > 0.3). Stavudine-lamivudine pharmacokinetic parameters were broadly comparable to heavier children. CONCLUSION: Exposure to nevirapine in African, HIV-infected infants with low body weight taking FDC tablets appears on average to be adequate, but due to large intersubject variability a relatively high proportion had subtherapeutic nevirapine C12 h levels, particularly those aged less than 5 months.

Authors: Fillekes, Q; Mulenga, V; Kabamba, D; Kankasa, C; Thomason, M

• Publication status: Published
• Journal: AIDS (London, England)
• Volume: 26
• Issue: 14
• Pages: 1795-1800
• Publication date: 2012-09-01
• DOI: 10.1097/qad.0b013e32835705fd
• EISSN: 1473-5571
• ISSN: 0269-9370
• Language: English
• Keywords: Zambia; Humans; Anti-HIV Agents; Infant; Drug Administration Schedule; Male; Viral Load; Infant, Newborn; Antiretroviral Therapy, Highly Active; Stavudine; Female; HIV Seropositivity; Drug Therapy, Combination; Nevirapine; Lamivudine; Body Weight; Drug Monitoring