Nevirapine concentrations in HIV-infected children treated with divided fixed-dose combination antiretroviral tablets in Malawi and Zambia.
until further notice
SourceAntiviral Therapy, 12, 2, (2007), pp. 253-260
Article / Letter to editor
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SubjectCTR 2: Clinical Pharmacology and physiology; N4i 2: Invasive mycoses and compromised host; N4i 3: Poverty-related infectious diseases; NCEBP 13: Infectious diseases and international health; UMCN 3.2: Cognitive neurosciences; UMCN 4.1: Microbial pathogenesis and host defense; CTR 2: Clinical Pharmacology and physiology
OBJECTIVE: To investigate nevirapine concentrations in African HIV-infected children receiving divided Triomune tablets (stavudine+lamivudine+nevirapine). DESIGN: Cross-sectional study. METHODS: Steady-state plasma nevirapine concentrations were determined in Malawian and Zambian children aged 8 months to 18 years receiving Triomune in routine outpatient settings. Predictors from height-for-age, body mass index (BMI)-for-age, age, sex, post-dose sampling time and dose/m2/day were investigated using centre-stratified regression with backwards elimination (P<0.1). RESULTS: Of the 71 Malawian and 56 Zambian children (median age 8.4 vs 8.5 years, height-for-age -3.15 vs -1.84, respectively), only 1 (3%) of those prescribed > or =300 mg/m2/day nevirapine had subtherapeutic concentrations (<3 mg/l) compared with 22 (23%) of those prescribed <300 mg/m2/day; most children with subtherapeutic nevirapine concentrations were taking half or quarter Triomune tablets. Lower nevirapine concentrations were independently associated with lower height-for-age (indicating stunting) (0.37 mg/l per unit higher [95% confidence interval (CI): -0.003, +0.74]; P=0.05), lower prescribed dose/m2 (+0.89 mg/l per 50 mg/m2 higher [95% CI: 0.32, 1.46]; P=0.002) and higher BMI-for-age (indicating lack of wasting) (-0.42 mg/l per unit higher [95% CI: -0.80, -0.04]; P=0.03). CONCLUSIONS: Currently available adult fixed-dose combination tablets are not well suited to children, particularly at younger ages: Triomune 30 is preferable to Triomune 40 because of the higher dose of nevirapine relative to stavudine. Further research is required to confirm that concentrations are reduced in stunted children but increased in wasted children. Development of appropriate paediatric fixed-dose combination tablets is essential if antiretroviral therapy is to be made widely available to children in resource-limited settings.
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