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Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients

Marzolini, Catiaa; Telenti, Amaliob; Decosterd, Laurent A.a; Greub, Gilbertb; Biollaz, Jérômea; Buclin, Thierrya

Clinical Science: Concise Communication

Objective Limited information exists on the clinical usefulness of drug level monitoring for efavirenz, a once-daily non-nucleoside reverse transcriptase inhibitor (NNRTI). The aim of this study was to determine whether efavirenz plasma concentration monitoring could predict treatment failure and central nervous system (CNS) tolerability.

Methods Blood samples were obtained from 130 HIV-infected patients receiving efavirenz in combination with other antiretroviral agents for more than 3 months. Efavirenz plasma concentrations were measured by high-performance liquid chromatography. An evaluation of CNS side-effects was performed and the viral load, CD4 cell count and other clinical and laboratory data were assessed. In 85 patients, these measures were repeated at 3 month intervals.

Results Efavirenz plasma levels (n = 226) were measured at an average of 14 h after drug intake. Drug concentrations ranged from 125 to 15 230 μg/l (median 2188). Large inter-patient (CV 118%) and limited intra-patient (CV 30%) variabilities were observed in efavirenz levels. Virological failure was observed in 50% of patients with low efavirenz levels (< 1000 μg/l) versus 22 and 18% in patients with 1000–4000 μg/l or more than 4000 μg/l, respectively. CNS toxicity was approximately three times more frequent in patients with high efavirenz levels (> 4000 μg/l) compared with patients with 1000–4000 μg/l.

Conclusion Treatment failure and CNS side-effects are associated with low and high efavirenz plasma levels, respectively. The important inter-individual variability in efavirenz levels strongly argues for dose adjustment on the basis of therapeutic drug monitoring to optimize treatment.

From the aDivision of Clinical Pharmacology, Department of Medicine, and bDivision of Infectious Diseases, University Hospital of Lausanne, Switzerland.

Received: 22 August 2000; accepted: 10 October 2000.

Sponsorship: This work was supported by a grant from the Swiss National Science Foundation (no. 3344-062092.00).

Correspondence to: Thierry Buclin, Division of Clinical Pharmacology, Beaumont 06-633, Department of Medicine, University Hospital (CHUV), 1011 Lausanne, Switzerland. Tel: +41 21 314 42 65; fax: +41 21 314 42 66; e-mail:

© 2001 Lippincott Williams & Wilkins, Inc.