JAC Advance Access originally published online on August 18, 2006
Journal of Antimicrobial Chemotherapy 2006 58(5):1090-1093; doi:10.1093/jac/dkl348
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Intracellular and plasma efavirenz concentrations in HIV-infected patients switching from successful protease inhibitor-based highly active antiretroviral therapy (HAART) to efavirenz-based HAART (SUSTIPHAR Study)
1 Department of Clinical Pharmacokinetics EA525, Victor Segalen Bordeaux 2 University Bordeaux, France, and Pharmacy Haut-Lévêque Hospital, CHU Bordeaux, Pessac, France 2 Department of Clinical Virology, Pellegrin Hospital CHU Bordeaux, France 3 Department of Pharmacokinetics and Toxicology, Rangueil-Larrey Hospital Toulouse, France 4 Department of Internal Medicine and Infectious Diseases, Haut-Lévêque Hospital CHU Bordeaux, Pessac, France
Received 28 February 2006; returned 12 May 2006; revised 18 July 2006; accepted 2 August 2006
*Correspondence address. Pharmacie Centrale, Hôpital Haut-Lévêque, CHU de Bordeaux, avenue de Magellan, 33604 Pessac, France. Tel: +33-557656812; Fax: +33-557656459; E-mail: dominique.breilh{at}chu-bordeaux.fr
Objectives: To assess intracellular and plasma efavirenz concentrations in HIV-infected patients who switched to efavirenz-based highly active antiretroviral therapy (HAART) from successful protease inhibitor-based HAART.
Patients and methods: A total of 49 patients were included in this observational cohort study. At inclusion, all patients had plasma HIV-RNA levels <50 copies/mL and switched to efavirenz combined with two nucleoside reverse transcriptase inhibitors. Intracellular and plasma concentrations were measured 12 h post-dose, 1 month (M1) and 6 months (M6) after starting efavirenz. Virological success (VS) was defined as plasma HIV-RNA level <50 copies/mL within the first 12 months and remaining undetectable at the end of the follow-up.
Results: VS was documented in 48 patients for at least 12 months (range 12–78 months). High inter-patient variabilities of intracellular and plasma efavirenz concentrations were observed (coefficients of variation >40%). At M1 and M6, respectively, median [Q1; Q3] intracellular efavirenz concentrations were 5300 [2830; 11 530] and 6790 [3870; 8790] ng/mL, median plasma efavirenz concentrations were 2050 [1600; 3100] and 2100 [1410; 2500] ng/mL. No correlation was found between intracellular and plasma concentrations. Plasma efavirenz levels exceeded the proposed threshold of 1000 ng/mL in 96% of patients from M1.
Conclusions: For moderately pre-treated HIV-infected patients with few mutations who switched to efavirenz from previous successful HAART, the proposed plasma efficacy-threshold was reached without any dosage adaptation. VS was maintained beyond 12 months, despite high inter-patient and intra-patient variabilities of intracellular and plasma efavirenz concentrations.
Keywords: pharmacokinetics , therapeutic drug monitoring , drug efflux , drug metabolism