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CNS penetration of ART in HIV-infected children

Malon Van den Hof1, Charlotte Blokhuis1, Sophie Cohen1

  • 1Department of Pediatric Infectious Diseases, Emma Children's Hospital/Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

The Journal of Antimicrobial Chemotherapy
|November 11, 2017
PubMed

Insights

Paediatric data on antiretroviral drug CNS penetration are limited. This study found adequate central nervous system (CNS) drug concentrations for some antiretrovirals in HIV-infected children, but suboptimal levels for others, despite viral suppression.

Area of Science:

  • Pharmacokinetics and drug metabolism
  • Neuroscience and neurology
  • Infectious diseases and virology

Background:

  • Limited paediatric data exist regarding the central nervous system (CNS) penetration of antiretroviral drugs.
  • Understanding CNS drug penetration is crucial for optimizing treatment in HIV-infected children.

Purpose of the Study:

  • To evaluate the CNS penetration of antiretroviral drugs in HIV-infected children.
  • To explore potential associations between antiretroviral drug concentrations in the CNS and neurocognitive function.

Main Methods:

  • Paired cerebrospinal fluid (CSF) and blood samples were collected from HIV-infected children (8-18 years) on combined antiretroviral therapy (ART).
  • Drug concentrations were measured, and CSF/plasma ratios were calculated to assess CNS penetration.
  • Neurocognitive function and blood-brain barrier permeability were evaluated.

Main Results:

  • Adequate CSF concentrations above the inhibitory concentration (IC50) were observed for lamivudine, lopinavir, efavirenz, and nevirapine.
  • Suboptimal CSF concentrations (below IC50) were noted for tenofovir, emtricitabine, and abacavir in a proportion of children.
  • CSF drug concentrations did not correlate with blood-brain barrier permeability or neurocognitive function outcomes.

Conclusions:

  • Long-term ART in HIV-infected children demonstrates adequate CNS penetration for certain antiretrovirals, including lamivudine, lopinavir, efavirenz, and nevirapine.
  • Potential suboptimal CNS drug levels for tenofovir, abacavir, and emtricitabine warrant further investigation.
  • Despite varying CNS penetration, combined ART effectively achieved viral suppression in the studied paediatric population.
Abstract

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