16th International AIDS Conference Toronto, Canada - August 13 - 18, 2006

NEVIRAPINE CONCENTRATIONS IN HIV-INFECTED CHILDREN TREATED WITH DIVIDED FIXED DOSE COMBINATION TABLETS IN MALAWI AND ZAMBIA

Int Conf AIDS. 2006 Aug 13-18;16 Abstract No. WeAb0305

Mulenga V.¹, Ellis J.², Ewings F.³, L'homme R.⁴, Chintu C.¹, van Oosterhout J.⁵, Chileshe R.¹, Molyneux E.², Gibb D.³, Burger D.4
¹ University Teaching Hospital, Paediatrics, Lusaka, Zambia, ² College of Medicine, Paediatrics, Blantyre, Malawi, ³ MRC Clinical Trials Unit, HIV Division, London, United Kingdom, ⁴ Radboud University Medical Centre, Clinical Pharmacy, Nijmegen, Netherlands, ⁵ College of Medicine, Medicine, Blantyre, Malawi

BACKGROUND: Some African HIV-infected children are treated with divided fixed dose combination (FDC) Triomune® (d4T + 3TC + nevirapine) tablets. There are few data on nevirapine pharmacokinetics in such children, in whom malnourishment is common.

METHODS: Steadty-state plasma nevirapine concentrations were determined in 127 HIV-infected children aged 3 months – 16 years who had received Triomune® in Malawi or Zambia. Centre-stratified regression with backwards elimination (p>0.1) was used to identify predictors from height-for-age, BMI-for-age, age, sex, post-dose sampling time and dose/m²/day.

RESULTS: The 71 Malawian children were similar ages (median 8.4 years), but more malnourished (BMI-for-age -0.89, height-for-age -3.15) and had longer post-dose sampling times 8.9 hours) than the 56 Zambian children (8.9 years, -0.50, -1.84, 3.5 hours respectively). The median (IQR) [range] nevirapine levels were 4.8 (2.8,6.5) [0.15,15.4] and 7.0 (5.4,10.5) [0.15, 17.1] mg/L in Malawian and Zambian children respectively.Only those on nearly adult dose (350 – 400mg nevirapine /day) received the target dose 300mg/m²/day (median 337mg/m² (IQR 303 – 366) [range 274 – 454], 2%<3mg/L (considered subtherapeutic)); those prescribed 50 – 200mg/day (quarter/half tablets) were more frequently underdosed (236mg/m² (217,267) [120 – 354], 21%<3mg/L), as were those prescribed >200-< 350mg (263mg/m² (260,271) [245-292], 21%<3mg/L). Lower height-for-age (indicating stunting) (+0.37/mgL per unit higher [95% CI -0.013, +0.75], p=0.06), lower prescribed dose/m² (+0.67 mg/L per 50mg/m² higher [+0.014, + 1.32], p=0.05) and youger age (+0.15mg/L per year older [-0.022, + 0.31], p=0.09) were independently associated with lower nevirapine levels. There was no significant independent effect of lower BMI-for-age (indicating wasting) (-0.33mg/L per unit higher [-0.76, +0.09], p=0.12), although this was a stronger predictor restricting to Malawian children (-0.51 [-1.01, -0.02], p=0.04).

CONCLUSIONS: To avoid nevirapine underdosing in young children, divided FDC triomune should be used with caution; nevirapine levels may be reduced in stunted but increased in wasted children. Further studies investigating these relationships are required.

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2006-08-13
WeAb0305

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