ABSTRACT: To determine the relationship between nutritional status and nevirapine exposure by comparing the pharmacokinetics of nevirapine in HIV-infected children of different ages with and without malnutrition receiving divided tablets of Triomune 30 (stavudine + lamivudine + nevirapine) in accordance with Malawi National Guidelines.
Children were recruited in weight-based dosage bands and nutritional status classified according to weight for height. Total and unbound plasma nevirapine concentrations were measured over a full dosing interval. Multivariate linear and logistic regression analyses were performed to determine the effects of malnutrition, age, dose and other factors on nevirapine exposure and likelihood of achieving therapeutic nevirapine trough concentrations.
Forty-three children were recruited (37 included for analysis). Mild to moderate malnutrition was present in 12 (32%) children; 25 (68%) were of normal nutritional status. There was no effect of malnutrition on any measure of total drug exposure or on the unbound fraction of nevirapine. Nevirapine exposure was strongly related to dose administered (P = 0.039) and to age (for every yearly increase in age there was an approximately 88% increase in the odds of achieving a therapeutic nevirapine concentration; P = 0.056, 95% confidence interval 0.983-3.585).
Use of divided adult Triomune 30 tablets in treating young children results in significant underdosing. No independent effect of malnutrition on total and unbound nevirapine exposures was observed. These data support the use of bespoke paediatric antiretroviral formulations.
Journal of Antimicrobial Chemotherapy 10/2009; 64(6):1251-9. · 5.07 Impact Factor
ABSTRACT: There are few data on plasma and intracellular pharmacokinetics (PK) of once-daily (q24h) nucleoside analogues in HIV-infected children.
Children aged 2-13 years receiving combination treatment containing lamivudine (3TC) (4 mg/kg) and/or abacavir (ABC) (8 mg/kg) twice daily (q12h) were included in this single-arm, open-label, crossover study. Intensive plasma PK sampling was performed at steady state, after which children switched to q24h dosing and PK sampling was repeated 4 weeks later. Daily area under the curve (AUC0-24) and peak level (Cmax) of q24h and q12h regimens were compared by geometric mean ratios (GMRs) with 90% confidence intervals (CIs). Children were followed for 24 weeks to evaluate safety and virological response.
24 children were enrolled, of whom 20 [median age (range) 5.6 (2.1-12.8) years] had evaluable PK data for 3TC (n=19) and/or ABC (n=14). GMRs of 3TC and ABC AUC0-24 and Cmax q24h versus q12h significantly exceeded 1.0. GMRs were not significantly different between children aged 2-6 versus 6-13 years old (P>0.08). Of note, 3TC Cmax values for both q12h and q24h were significantly lower in children aged 2-6 versus 6-13 years old. No child discontinued due to adverse events. At baseline, 16 out of 20 children had a viral load <100 copies/ml compared with 17 out of 19 at week 24.
AUC0-24 and Cmax of both 3TC and ABC q24h were not inferior to q12h dosing in children. Insufficient results were obtained concerning intracellular levels of the active triphosphate moieties of both agents. Virological data did not indicate a marked difference in antiviral activity between q12h and q24h regimens.
Antiviral therapy 01/2005; 10(2):239-46. · 3.16 Impact Factor
ABSTRACT: Differences in virologic response were compared in 32 HIV-infected children with a nelfinavir trough concentration either below (n=7) or above (n=25) 0.8 mg/L. Virologic response at week 48 was observed in 29% of children with subtherapeutic nelfinavir troughs versus 80% in children with therapeutic nelfinavir troughs (P=.02).
Journal of Pediatrics 10/2004; 145(3):403-5. · 4.11 Impact Factor