Pharmacokinetics of rifampicin and isoniazid in patients with HIV–tuberculosis coinfection receiving efavirenz-based antiretroviral treatment: an ANRS12292–RIFAVIRENZ sub-study

作者：Thibaut Gelé, Daniel Atwine, Elisabeth Baudin, Winnie Muyindike, Kenneth Mworozi, Racheal Kyohairwe, Keneth Kananura, Susan Logoose, Dan Nyehangane, Deborah Nanjebe, Valérie Furlan, A M Taburet, Maryline Bonnet, Aurélie Barrail‐Tran, the ANRS12292 Rifavirenz study group, F-X Blanc, Thomas S. Harrison, Laurent A. Décosterd, Alexandra Calmy, Amina Jindani, Pauline Justumus, Y Mendy, Christophe Michon, Grace Muzanye, Helen McIlleron, Bruno Falissard · 发表于：Journal of Antimicrobial Chemotherapy · 年份：2025 · DOI：10.1093/jac/dkaf319 · 被引用次数：3 · 研究领域：Tuberculosis Research and Epidemiology、HIV/AIDS drug development and treatment、Pneumocystis jirovecii pneumonia detection and treatment

BACKGROUND: Increasing rifampicin dosing is considered a potent strategy for shortening TB treatment duration. Although previous data among patients with HIV-TB coinfection has shown that doubling rifampicin dosing had a small effect on EFV concentrations, its effect on the pharmacokinetics (PK) of antituberculosis drugs remains lacking in this population. OBJECTIVES: To compare the PK of rifampicin and isoniazid with and without EFV co-administration in patients with HIV-TB coinfection using two rifampicin dosing regimens (10 and 20 mg/kg/day) and EFV dosing (600 and 800 mg q24h). METHODS: Ninety-seven patients were assigned to three arms in a randomized clinical trial conducted in Uganda. Plasma concentrations of rifampicin, isoniazid, and acetyl-isoniazid were measured. PK parameters were estimated, and statistical comparisons were made using geometric mean ratios, 90% CIs and the pre-set 0.80-1.25 interval. RESULTS: Doubling rifampicin dosing increased its Cmax and AUClast almost 3-fold. Adding EFV decreased rifampicin AUClast by 34%-40%. Isoniazid AUClast was unaffected with EFV 600 mg q24h but decreased with EFV 800 mg q24h by 23%. EFV increased acetyl-isoniazid concentrations, suggesting enhanced acetylation activity. At 10 mg/kg of rifampicin, 88% of patients had Cmax below the therapeutic range. However, at 20 mg/kg of rifampicin, 87% of patients achieved therapeutic concentrations, ensuring effective treatment. CONCLUSIONS: The study highlights the importance of adj...