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

Jason F. Okulicz, Greg A. Grandits, Jacqueline A. French, Jomy M. George, David M. Simpson, Gretchen L. Birbeck, Anuradha Ganesan, Amy C. Weintrob, Nancy Crum-Cianflone, Tahaniyat Lalani, Michael L. Landrum

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18 Scopus citations


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.

Original languageEnglish (US)
Article number18
JournalAIDS Research and Therapy
StatePublished - May 16 2011

Bibliographical note

Funding Information:
The content of this publication is the sole responsibility of the authors and does not necessarily reflect the views or policies of the NIH or the Department of Health and Human Services, the DoD or the Departments of the Army, Navy or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government. This work was presented, in part, at the 18th Conference on Retroviruses and Opportunistic Infections, Boston, MA, USA. The Infectious Disease Clinical Research Program HIV Working Group includes Mark Kortepeter, Helen Chun, Cathy Decker, Susan Fraser, Joshua Hartzell, Gunther Hsue, Arthur Johnson, Alan Lifson, Grace Macalino, Robert O’Connell, John Powers, Roseanne Ressner, Edmund Tramont, Tyler Warkentian, Paige Waterman, Sheila Peel, Connor Eggleston, Scott Merritt, Susan Banks, Michael Zapor, Brian Agan, Michelle Linfesty, Mary Bavaro, Timothy Whitman, Glenn Wortmann, and Lynn Eberly. Support for this work (IDCRP-000-03) was provided by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense (DoD) program executed through the Uniformed Services University of the Health Sciences. This project has been funded in whole, or in part, with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), under Inter-Agency Agreement Y1-AI-5072.


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