Abiy Habtewold1,2, Eyasu Makonnen2, Wondwossen Amogne3,4, Getnet Yimer1,2, Getachew Aderaye3, Leif Bertilsson1, Jürgen Burhenne5, Eleni Aklillu1. 1. Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, C-168, Karolinska Institutet, 141 86 Stockholm, Sweden. 2. Department of Pharmacology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia. 3. Department of Internal Medicine, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia. 4. Department of Medicine, Division of Infectious Diseases, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden. 5. Department of Clinical Pharmacology & Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany.
Abstract
AIMS: The current HIV treatment guidelines are inconsistent about the need for weight-based efavirenz dose adjustment during rifampicin containing antituberculosis (anti-TB) cotreatment. We investigated effect of rifampicin-based anti-TB cotreatment on plasma efavirenz exposure and treatment outcome, considering effect of CYP2B6 genotype and bodyweight. PATIENTS & METHODS: HIV-only (arm 1, n = 285) or TB-HIV (arm 2, n = 208) coinfected patients were enrolled and received efavirenz-based ART alone or with rifampicin-based anti-TB therapy, respectively. Plasma efavirenz concentrations at 4th and 16th weeks, viral load and CD4 cell count at 24th and 48th weeks were determined. RESULTS: The mean plasma efavirenz concentration at weeks 4 (p = 0.03) and 16 (p = 0.08) was inconsistently higher in arm 2 than arm 1, mainly in CYP2B6*6 carriers. Effect of bodyweight on efavirenz pharmacokinetics was significant only in arm 1, but not in arm 2. Proportion of patients with nondetectable viral load (≤50 copies/ml) at week 24 was higher in arm 1 than arm 2 patients (91.0 vs 76.3%; p = 0.002), but no significant difference was observed at week 48 (89.5 vs 87.8%; p = 0.22). CONCLUSION: Rifampicin-based anti-TB cotreatment has no significant influence on long-term efavirenz plasma exposure and efficacy. Hence, there is no need to increase the dose of efavirenz during concomitant rifampicin-based anti-TB cotreatment in the sub-Saharan African population.
AIMS: The current HIV treatment guidelines are inconsistent about the need for weight-based efavirenz dose adjustment during rifampicin containing antituberculosis (anti-TB) cotreatment. We investigated effect of rifampicin-based anti-TB cotreatment on plasma efavirenz exposure and treatment outcome, considering effect of CYP2B6 genotype and bodyweight. PATIENTS & METHODS: HIV-only (arm 1, n = 285) or TB-HIV (arm 2, n = 208) coinfected patients were enrolled and received efavirenz-based ART alone or with rifampicin-based anti-TB therapy, respectively. Plasma efavirenz concentrations at 4th and 16th weeks, viral load and CD4 cell count at 24th and 48th weeks were determined. RESULTS: The mean plasma efavirenz concentration at weeks 4 (p = 0.03) and 16 (p = 0.08) was inconsistently higher in arm 2 than arm 1, mainly in CYP2B6*6 carriers. Effect of bodyweight on efavirenz pharmacokinetics was significant only in arm 1, but not in arm 2. Proportion of patients with nondetectable viral load (≤50 copies/ml) at week 24 was higher in arm 1 than arm 2patients (91.0 vs 76.3%; p = 0.002), but no significant difference was observed at week 48 (89.5 vs 87.8%; p = 0.22). CONCLUSION:Rifampicin-based anti-TB cotreatment has no significant influence on long-term efavirenz plasma exposure and efficacy. Hence, there is no need to increase the dose of efavirenz during concomitant rifampicin-based anti-TB cotreatment in the sub-Saharan African population.
Authors: Mutsa Bwakura Dangarembizi; Pearl Samson; Edmund V Capparelli; Carolyn Bolton Moore; Patrick Jean-Philippe; Stephen A Spector; Nahida Chakhtoura; Alex Benns; Bonnie Zimmer; Lynette Purdue; Chivon Jackson; Carole Wallis; Jennifer L Libous; Ellen G Chadwick Journal: J Acquir Immune Defic Syndr Date: 2019-08-01 Impact factor: 3.731
Authors: Carola R Röhrich; Britt I Drögemöller; Ogechi Ikediobi; Lize van der Merwe; Nelis Grobbelaar; Galen E B Wright; Nathaniel McGregor; Louise Warnich Journal: AIDS Res Hum Retroviruses Date: 2016-01-29 Impact factor: 2.205