Steady-state nevirapine, lamivudine and stavudine levels in Malawian HIV-infected children on antiretroviral therapy using split Triomune 30 tablets.

BACKGROUND: Children remain under-represented in national antiretroviral treatment (ART) programmes in settings with limited resources and high HIV prevalence. In Malawi, an increasing number of HIV-infected children have been started on ART with split tablets of an adult fixed-dose combination drug in the past few years. In 2006, the national paediatric ART regime was changed from Triomune 40 (T40) to Triomune 30 (T30). METHODS: This was a cross-sectional study conducted at the paediatric ART clinic in Blantyre (Malawi) from September 2006 to July 2007. Children taking T30 for > 6 weeks from each dosing weight band (<5, 5-<8, 8-<12, 12-<14, 14-<19, 19-<26, 26-<30 and > or = 30 kg) were recruited. Plasma drug concentration, CD4+ T-cell count and HIV viral load were measured. RESULTS: A total of 74 children were analysed. The median nevirapine (NVP) concentration was 7.35 mg/l. A therapeutic NVP plasma level > 3 mg/l was found in 62 (87.8%) children. A subtherapeutic NVP level (< 3 mg/l) occurred significantly more often in children treated with T30 doses between one-quarter tablet once daily and one-half tablet twice daily (P=0.035). Median prescribed NVP dose was 342 mg/m(2)/day, but 13 (17.6%) children received a dose below the recommended dose of 300 mg/m(2)/day. Compared with a historical control, the median prescribed NVP dose was increased (from 243 to 342 mg/m(2)/day). CONCLUSIONS: Our findings indicate that with the Malawian T30-based ART regime, the majority (87.8%) of children in the study group achieved a therapeutic NVP level. However, treatment remains suboptimal especially for young children receiving T30 dosages less than or equal to one-half tablets twice daily and child appropriate formulations are warranted.

Pharmacokinetics of nevirapine in HIV-infected children with and without malnutrition receiving divided adult fixed-dose combination tablets.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Comparison of previous and present World Health Organization clinical staging criteria in HIV-infected Malawian children.

In many settings, HIV infected children are looked after with limited access to CD4 cell count or viral load. The decision to initiate antiretroviral therapy (ART) is made clinically, based on the WHO paediatric staging criteria, which were revised in 2006. Results of using new and old criteria were compared. Of 694 children, 626 (90.2%) fulfilled criteria to start ART when applying the new WHO staging guidelines, whereas 330 (47.6%) children were eligible for ART when using the old WHO criteria. This signifies a marked rise in the number of paediatric patients qualifying for ART on clinical grounds.