Efavirenz trough levels are not associated with virological failure throughout therapy with 800 mg daily and a rifampicin-containing antituberculosis regimen

• Published in: Journal of antimicrobial chemotherapy Vol. 58; no. 5; pp. 1017 - 1023
• Main Authors: Lopez-Cortes, Luis F., Ruiz-Valderas, Rosa, Ruiz-Morales, Josefa, Leon, Eva, Campos, Antonio Vergara de, Marin-Niebla, Ana, Marquez-Solero, Manuel, Lozano, Fernando, Valiente, Rebeca
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.11.2006; Oxford Publishing Limited (England)
• Subjects: Adult; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Anti-HIV Agents - pharmacokinetics; Antibiotics, Antitubercular - administration & dosage; Antibiotics, Antitubercular - adverse effects; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacterial diseases; Benzoxazines; Biological and medical sciences; Chemotherapy; Clinical trials; Drug Administration Schedule; Drug Interactions; Female; HIV; HIV - isolation & purification; HIV infection; HIV Infections - drug therapy; HIV Infections - metabolism; HIV Infections - microbiology; Human bacterial diseases; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Male; Medical sciences; Middle Aged; Mycobacterium; Mycobacterium tuberculosis - isolation & purification; Oxazines - administration & dosage; Oxazines - adverse effects; Oxazines - pharmacokinetics; pharmacokinetics; Pharmacology; Pharmacology. Drug treatments; Prospective Studies; Reverse Transcriptase Inhibitors - classification; Rifampin - administration & dosage; Rifampin - adverse effects; Tuberculosis; Tuberculosis - drug therapy; Tuberculosis - metabolism; Tuberculosis - virology; Tuberculosis and atypical mycobacterial infections; 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; Mycobacterial infection; Efavirenz; Rifampicin; Reverse transcriptase inhibitor; Antiviral; Antituberculous agent; Protein synthesis inhibitor; Failure; Immunopathology; Enzyme; Transferases; Enzyme inhibitor; AIDS; Immune deficiency; Infection; Allosteric inhibitor; Nucleotidyltransferases; Antibiotic; Treatment; Tuberculosis; Viral disease; Bacteriosis; Antibacterial agent; Pharmacokinetics; HIV infection
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkl357

Objectives: To assess the safety and efficacy of efavirenz 800 mg daily in HIV-infected patients with tuberculosis receiving a rifampicin-containing regimen and to analyse whether a relationship exists between efavirenz Cmin and its virological efficacy. Methods: Prospective, open-labelled study including HIV-infected patients on rifampicin and efavirenz 800 mg daily. Treatment adherence, adverse events (AEs), HIV-RNA levels, CD4 cell counts and efavirenz Cmin during and after finishing rifampicin treatment were evaluated. Results: Eighty patients met the inclusion criteria. A permanent drug withdrawal due to AEs occurred in 10 patients, 5 attributable to efavirenz, and 10 patients were lost to follow-up before the third month. Efavirenz Cmin levels with 800 mg plus rifampicin were similar to those with 600 mg after withdrawing rifampicin. Sixty patients were included in the efficacy analysis, eight experiencing virological failure. No relation was observed between the rate of virological failure and efavirenz Cmin, previous antiretroviral treatment or not, baseline CD4 counts or RNA-HIV. The only variable related to virological failure was irregular adherence [odds ratio, 81 (95% CI: 5–1280); P = 0.002]. Conclusions: Given the lack of a demonstrated relationship between efavirenz Cmin and its efficacy in our study, a firm recommendation cannot be made to always increase the dose to 800 mg/day when concomitantly given with rifampicin, but it seems a cautious approach to maintain the same efavirenz plasma levels as with 600 mg daily without rifampicin. Patients weighing <55 kg and also black, Asian and Hispanic subjects in whom genetic-based increased efavirenz plasma levels and rates of AEs have been observed may benefit from a dose of 600 mg.