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Suboptimal cotrimoxazole prophylactic concentrations in HIV-infected children according to the WHO guidelines

Claire Pressiat1, Veronique Mea-Assande2, Caroline Yonaba3

  • 1Paris Descartes University, EA 7323, Paris, France.

British Journal of Clinical Pharmacology
|August 12, 2017
PubMed

Insights

This study evaluated World Health Organization (WHO) recommended prophylactic doses of cotrimoxazole (sulfamethoxazole and trimethoprim) in HIV-infected children. Results indicate that weight-based dosing is necessary to ensure effective treatment and comparable drug exposure to adults.

Area of Science:

  • Pediatric Pharmacology
  • Infectious Diseases
  • HIV/AIDS Treatment

Background:

  • Cotrimoxazole prophylaxis (sulfamethoxazole/trimethoprim) is crucial for preventing opportunistic infections in HIV-infected children.
  • Current World Health Organization (WHO) dosing guidelines may not ensure adequate drug exposure in pediatric populations.

Purpose of the Study:

  • To evaluate the prophylactic doses of cotrimoxazole recommended by the WHO in HIV-infected children.
  • To determine optimal weight-based dosing regimens for sulfamethoxazole (SMX) and trimethoprim (TMP) in this population.

Main Methods:

  • A clinical study involving 136 HIV-infected children receiving lopinavir-based antiretroviral therapy and cotrimoxazole prophylaxis.
  • Nonlinear mixed-effects modeling was used to analyze plasma concentrations and investigate pharmacokinetic profiles.
  • Simulations were performed to evaluate different administration schemes and their impact on drug exposure.

Main Results:

  • A significant influence of body size on SMX and TMP pharmacokinetics was observed, justifying a dose-per-kilogram approach.
  • WHO-recommended oral dosing for children weighing 10-15 kg resulted in significantly lower SMX and TMP exposure compared to adults.
  • Simulated regimens of 30 mg/kg SMX and 6 mg/kg TMP (5-10 kg group) and 25 mg/kg SMX and 5 mg/kg TMP (10-15 kg group) were identified as more suitable.

Conclusions:

  • HIV-infected children exhibit lower cotrimoxazole exposure than adults, potentially reducing treatment effectiveness.
  • A weight-based dosing scheme is proposed to achieve comparable drug exposure to adults.
  • Optimized dosing is essential for effective prophylaxis against opportunistic infections in pediatric HIV patients.
Abstract

Keywords:
HIVchildrenpharmacokineticssulfamethoxazoletrimethoprim

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