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)

• Published in: Journal of antimicrobial chemotherapy Vol. 58; no. 5; pp. 1090 - 1093
• Main Authors: Djabarouti, Sarah, Breilh, Dominique, Pellegrin, Isabelle, Lavit, Michel, Camou, Fabrice, Caubet, Olivier, Fleury, Hervé, Saux, Marie-Claude, Pellegrin, Jean-Luc
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-11-2006; Oxford Publishing Limited (England)
• Subjects: Adult; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; Antiretroviral Therapy, Highly Active - methods; Benzoxazines; Biological and medical sciences; Chemotherapy; Cohort Studies; drug efflux; drug metabolism; Female; HIV; HIV - genetics; HIV - isolation & purification; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - metabolism; HIV Protease Inhibitors - administration & dosage; HIV Protease Inhibitors - blood; HIV Protease Inhibitors - pharmacokinetics; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Male; Medical sciences; Middle Aged; Oxazines - administration & dosage; Oxazines - blood; Oxazines - pharmacokinetics; pharmacokinetics; Pharmacology; Pharmacology. Drug treatments; Protease inhibitors; Reverse Transcriptase Inhibitors - administration & dosage; Reverse Transcriptase Inhibitors - blood; Reverse Transcriptase Inhibitors - pharmacokinetics; RNA, Viral - blood; therapeutic drug monitoring; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Antiretroviral agent; Benzoxazine derivatives; RNA-directed DNA polymerase; Acetylenic compound; Non nucleoside compound; Efavirenz; Therapeutic drug monitoring; drug efflux; Reverse transcriptase inhibitor; drug metabolism; Antiviral; Drug; Immunopathology; Enzyme; Transferases; Enzyme inhibitor; AIDS; Metabolism; Immune deficiency; Switching; Infection; Allosteric inhibitor; Nucleotidyltransferases; Chemotherapy; Viral disease; Intracellular; Pharmacokinetics; Protease inhibitor
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkl348

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.