Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1097/QAD.0b013e32835705fd

Type

Journal article

Journal

AIDS

Publication Date

10/09/2012

Volume

26

Pages

1795 - 1800

Keywords

Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Body Weight, Drug Administration Schedule, Drug Monitoring, Drug Therapy, Combination, Female, HIV Seropositivity, Humans, Infant, Infant, Newborn, Lamivudine, Male, Nevirapine, Stavudine, Viral Load, Zambia