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Efavirenz Dose Reduction Is Safe in Patients With High Plasma Concentrations and May Prevent Efavirenz Discontinuations

van Luin, Matthijs PharmD*†; Gras, Luuk MSc; Richter, Clemens MD, PhD§; van der Ende, Marchina E MD, PhD; Prins, Jan M MD, PhD; Wolf, Frank de MD, PhD‡#; Burger, David M PharmD, PhD*; Wit, Ferdinand W MD, PhD**

JAIDS Journal of Acquired Immune Deficiency Syndromes: October 2009 - Volume 52 - Issue 2 - p 240-245
doi: 10.1097/QAI.0b013e3181b061e6
Clinical Science

Objective: To establish whether efavirenz dose reduction in patients with high plasma concentrations prevents toxicity-induced efavirenz discontinuations.

Methods: HIV-infected patients with a high efavirenz plasma concentration (≥4.0 mg/L) while using efavirenz 600 mg once daily as part of their highly active antiretroviral therapy regimen were selected from the AIDS Therapy Evaluation in The Netherlands cohort study. These patients were classified into 2 groups. The reduced-dose group contained all patients who underwent dose reduction after the high plasma concentration measurement; the standard-dose group consisted of patients who had no dose reduction. Kaplan-Meier and Cox proportional hazards analysis were used to assess the impact of dose reduction on toxicity-induced efavirenz discontinuations.

Results: One hundred eighty patients with high plasma efavirenz levels were included, 47 of them subsequently had their efavirenz dose reduced from 600 mg to 400 mg once-daily, which resulted in a 41% decrease in the median efavirenz plasma concentration. At week 48, the Kaplan-Meier estimated cumulative incidence of toxicity-induced efavirenz discontinuations was 11.5% in patients who continued the standard dose versus 2.3% in patients who had a dose reduction; P = 0.066 (log-rank test). Dose reduction was not associated with loss of virological suppression.

Conclusions: Dose reduction may prevent toxicity-induced discontinuations in patients with high efavirenz plasma concentrations, whereas not compromising virological efficacy.

From the *Department of Clinical Pharmacy, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands; †Department of Clinical Pharmacy, Rijnstate Hospital, Arnhem, The Netherlands; ‡HIV Monitoring Foundation, Amsterdam, The Netherlands; §Department of Internal Medicine, Rijnstate Hospital, Arnhem, The Netherlands; ‖Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands; ¶Department of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, Amsterdam, The Netherlands; #Department of Infectious Disease Epidemiology, Imperial College, London, United Kingdom; and **Center for Poverty-related Communicable Diseases, Academic Medical Center, Amsterdam, The Netherlands.

Received for publication December 3, 2008; accepted April 29, 2009.

Presented at the 11th European AIDS conference/EACS, October 24-27, 2007, Madrid, Spain.

Sources of support: none.

Correspondence to: Matthijs van Luin, PharmD, Department of Clinical Pharmacy, 864 Radboud University Nijmegen Medical Center, Nijmegen, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands (e-mail:

© 2009 Lippincott Williams & Wilkins, Inc.