title: Is there a need to increase the dose of efavirenz during concomitant rifampicin-based antituberculosis therapy in sub-Saharan Africa? The HIV-TB pharmagene study.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, C-168, Karolinska Institutet, 141 86 Stockholm, Sweden.|Department of Pharmacology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
authors.forename: Abiy
authors.initials: A
authors.lastname: Habtewold
authors.affiliation: Department of Pharmacology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
authors.forename: Eyasu
authors.initials: E
authors.lastname: Makonnen
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.|Department of Medicine, Division of Infectious Diseases, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Wondwossen
authors.initials: W
authors.lastname: Amogne
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, C-168, Karolinska Institutet, 141 86 Stockholm, Sweden.|Department of Pharmacology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
authors.forename: Getnet
authors.initials: G
authors.lastname: Yimer
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
authors.forename: Getachew
authors.initials: G
authors.lastname: Aderaye
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, C-168, Karolinska Institutet, 141 86 Stockholm, Sweden.
authors.forename: Leif
authors.initials: L
authors.lastname: Bertilsson
authors.affiliation: Department of Clinical Pharmacology & Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Burhenne
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, C-168, Karolinska Institutet, 141 86 Stockholm, Sweden.
authors.forename: Eleni
authors.initials: E
authors.lastname: Aklillu
mesh_terms: D000328:Adult; D017954:Africa South of the Sahara; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D048588:Benzoxazines / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count / Q000379:methods; D060085:Coinfection / Q000188:drug therapy; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6 / Q000378:metabolism; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D010597:Pharmacogenetics / Q000379:methods; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D012293:Rifampin / Q000627:therapeutic use*; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D000904:Antibiotics, Antitubercular; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D065702:Cytochrome P-450 CYP2B6; C098320:efavirenz; D012293:Rifampin
keywords: CYP2B6; Ethiopia; HIV/AIDS; efavirenz; rifampicin; sub-Saharan Africa; treatment guideline; tuberculosis