Pharmacokinetics of antiretroviral drug varies with formulation in the target population of children with HIV-1.

The bioequivalence of formulations is usually evaluated in healthy adult volunteers. In our study in 19 HIV-1-infected Ugandan children (1.8-4 years of age, weight 12 to <15 kg) receiving zidovudine, lamivudine, and abacavir solutions twice a day for ≥24 weeks, the use of scored tablets allowed comparison of plasma pharmacokinetics of oral solutions vs. tablets. Samples were collected 0, 1, 2, 4, 6, 8, and 12 h after each child's last morning dose of oral solution before changing to scored tablets of Combivir (coformulated zidovudine + lamivudine) and abacavir; this was repeated 4 weeks later. Dose-normalized area under curve (AUC)(0-12) and peak concentration (C(max)) for the tablet formulation were bioequivalent with those of the oral solution with respect to zidovudine and abacavir (e.g., dose-normalized geometric mean ratio (dnGMR) (tablet:solution) for zidovudine and abacavir AUC(0-12) were 1.01 (90% confidence interval (CI) 0.87-1.18) and 0.96 (0.83-1.12), respectively). However, lamivudine exposure was ~55% higher with the tablet formulation (AUC(0-12) dnGMR = 1.58 (1.37-1.81), C(max) dnGMR = 1.55 (1.33-1.81)). Although the clinical relevance of this finding is unclear, it highlights the impact of the formulation and the importance of conducting bioequivalence studies in target pediatric populations.

Tuberculosis in human immunodeficiency virus infected Ugandan children starting on antiretroviral therapy.

OBJECTIVE: To identify the incidence of tuberculosis (TB) in human immunodeficiency virus (HIV) infected children in a resource-limited setting before and after initiation of antiretroviral therapy (ART), and to assess the impact of TB screening by tuberculin skin testing and clinical history. METHODS: A retrospective cohort study of 1806 HIV-infected children and adolescents (age <18 years) initiating ART from 2003 to 1 July 2006 in Kampala, Uganda. A TB screening program was instituted clinic-wide in January 2006. RESULTS: Of 311 (17.2%) HIV-infected children, 171 had been diagnosed with TB before and 140 after ART initiation. During the first 100 days of ART, risk of a new TB diagnosis was 2.7-fold higher compared to the pre-ART period (RR 2.7, 95%CI 2.1-3.5, P < 0.001). After 100 days of ART, the TB incidence rate decreased to below pre-ART levels (RR 0.41, 95%CI 0.30-0.54, P = 0.002). After TB screening was instituted in 2006, the proportion of new TB cases diagnosed after starting ART decreased by 70% (95%CI 51-82, P < 0.001), abating the early excess risk. CONCLUSIONS: TB is common among African children and adolescents initiating ART in sub-Saharan Africa. More aggressive screening for active TB before starting ART can diminish the rate of TB during immune reconstitution. Future studies are needed to determine optimal screening practices for HIV-infected children.