The impact of enzyme-inducing antiepileptic drugs on antiretroviral drug levels: a case-control study

Epilepsy Res. 2013 Feb;103(2-3):245-53. doi: 10.1016/j.eplepsyres.2012.07.009. Epub 2012 Jul 24.

Abstract

Purpose: To evaluate the impact of enzyme-inducing antiepileptic drugs (EI-AEDs) on serum antiretroviral (ARV) levels in patients with HIV.

Methods: Data from the U.S. Military HIV Natural History Study were screened to identify participants taking ARVs with EI-AEDs and controls taking ARVs with non enzyme-inducing AEDs (NEI-AEDs). The proportion of serum ARV levels below the recommended minimum concentrations (C(min)) was compared between these groups.

Results: ARV levels were available for 10 individuals exposed to 16 intervals on combined ARVs/EI-AEDs (phenytoin and carbamazepine) and for 25 controls exposed to 30 overlap intervals on combined ARVs/NEI-AEDs. The percentage of overlap intervals with ≥1 ARV levels below C(min) was higher in the EI-AED group than in controls (37.5% vs. 23.3%; p=0.124). After excluding intervals associated with serum levels of EI-AEDs below the reference range (n=6), the proportion of intervals with ≥1 ARV level below C(min) was significantly greater among EI-AED recipients (60%) compared to controls (23.3%; p=0.008).

Conclusions: ARV levels below C(min) were more common in participants receiving EI-AEDs, the difference being statistically significant for intervals associated with EI-AED levels within the reference range. These data suggest that, in agreement with current guidelines, EI-AEDs should be avoided in patients receiving ARV therapy.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Anti-Retroviral Agents / blood*
  • Anti-Retroviral Agents / therapeutic use
  • Anticonvulsants / blood*
  • Anticonvulsants / therapeutic use
  • Case-Control Studies
  • Drug Interactions / physiology
  • Enzyme Induction / drug effects
  • Enzyme Induction / physiology
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy
  • HIV Infections / enzymology*
  • Humans
  • Male
  • Middle Aged

Substances

  • Anti-Retroviral Agents
  • Anticonvulsants