Open Access Research

Virologic outcomes of HAART with concurrent use of cytochrome P450 enzyme-inducing antiepileptics: a retrospective case control study

Jason F Okulicz12*, Greg A Grandits13, Jacqueline A French4, Jomy M George5, David M Simpson6, Gretchen L Birbeck7, Anuradha Ganesan18, Amy C Weintrob19, Nancy Crum-Cianflone110, Tahaniyat Lalani1, Michael L Landrum12 and the Infectious Disease Clinical Research Program (IDCRP) HIV Working Group

Author Affiliations

1 Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD, USA

2 Infectious Disease Service, Brooke Army Medical Center, San Antonio TX, USA

3 Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA

4 NYU Comprehensive Epilepsy Center, New York, NY, USA

5 Department of Pharmacy Practice and Administration, Philadelphia College of Pharmacy, Philadelphia, PA, USA

6 Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA

7 International Neurologic & Psychiatric Epidemiology Program, Michigan State University, East Lansing, MI, USA

8 Division of Infectious Diseases, National Naval Medical Center, Bethesda, MD, USA

9 Infectious Disease Service, Walter Reed Army Medical Center, Washington, DC, USA

10 Infectious Disease Clinic, Naval Medical Center San Diego, San Diego, CA, USA

For all author emails, please log on.

AIDS Research and Therapy 2011, 8:18  doi:10.1186/1742-6405-8-18

Published: 16 May 2011

Abstract

Background

To evaluate the efficacy of highly-active antiretroviral therapy (HAART) in individuals taking cytochrome P450 enzyme-inducing antiepileptics (EI-EADs), we evaluated the virologic response to HAART with or without concurrent antiepileptic use.

Methods

Participants in the US Military HIV Natural History Study were included if taking HAART for ≥6 months with concurrent use of EI-AEDs phenytoin, carbamazepine, or phenobarbital for ≥28 days. Virologic outcomes were compared to HAART-treated participants taking AEDs that are not CYP450 enzyme-inducing (NEI-AED group) as well as to a matched group of individuals not taking AEDs (non-AED group). For participants with multiple HAART regimens with AED overlap, the first 3 overlaps were studied.

Results

EI-AED participants (n = 19) had greater virologic failure (62.5%) compared to NEI-AED participants (n = 85; 26.7%) for the first HAART/AED overlap period (OR 4.58 [1.47-14.25]; P = 0.009). Analysis of multiple overlap periods yielded consistent results (OR 4.29 [1.51-12.21]; P = 0.006). Virologic failure was also greater in the EI-AED versus NEI-AED group with multiple HAART/AED overlaps when adjusted for both year of and viral load at HAART initiation (OR 4.19 [1.54-11.44]; P = 0.005). Compared to the non-AED group (n = 190), EI-AED participants had greater virologic failure (62.5% vs. 42.5%; P = 0.134), however this result was only significant when adjusted for viral load at HAART initiation (OR 4.30 [1.02-18.07]; P = 0.046).

Conclusions

Consistent with data from pharmacokinetic studies demonstrating that EI-AED use may result in subtherapeutic levels of HAART, EI-AED use is associated with greater risk of virologic failure compared to NEI-AEDs when co-administered with HAART. Concurrent use of EI-AEDs and HAART should be avoided when possible.