title: Efavirenz and rifampicin in the South African context: is there a need to dose-increase efavirenz with concurrent rifampicin therapy?
abstract: BACKGROUND
  Increasing efavirenz (EFV) dose from 600 mg to 800 mg daily has been suggested with concomitant rifampicin (RFN), as induction of cytochrome P450 isoenzymes may reduce EFV plasma concentrations.
  
  
  METHODS
  Individuals from the CIPRA-South Africa cohort taking EFV-based antiretroviral therapy with concomitant tuberculosis (TB) were dosed with either increased (800 mg) or standard (600 mg) dose EFV during TB treatment. After TB therapy, all individuals took 600 mg EFV. Two mid-dosing interval EFV concentrations were determined from each individual: after 4 weeks of concomitant EFV and RFN therapy, and ≥4 weeks after TB therapy completion. Mid-dosing interval EFV concentrations were compared within individuals using the Wilcoxon signed-rank test.
  
  
  RESULTS
  Paired samples were collected from 72 individuals. Overall, 45 (63%) were women and median weight was 59 kg (IQR 52-67). At antiretroviral therapy start, median CD4(+) T-cell count was 114 cells/mm(3) (IQR 37-165), median viral load was 5.5 log (IQR 5.1-5.9). A total of 38 (53%) individuals took 800 mg EFV during TB treatment and 34 (47%) took 600 mg. EFV concentrations in the 800 mg group were higher with RFN (2.9 mg/l [IQR 1.8-5.6]) than without (2.1 mg/l [IQR 1.4-3.0]; P=0.0003). There was no significant difference in EFV concentrations with RFN (2.4 mg/l [IQR 1.2-5.1]) or without (2.2 mg/l [IQR 1.4-3.7]) in the 600 mg group. There was no increase in EFV-linked adverse effects in either group. The proportion of virologically suppressed individuals at 48 weeks was similar in both groups.
  
  
  CONCLUSIONS
  EFV concentrations were significantly increased in the EFV 800 mg group on RFN. There was no significant decrease in EFV concentrations when on RFN in the 600 mg group. Dose escalation of EFV 600 mg to 800 mg is not required during concomitant TB therapy in South Africa.
authors.affiliation: Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. catherine.orrell@hiv-research.org.za
authors.forename: Catherine
authors.initials: C
authors.lastname: Orrell
authors.forename: Karen
authors.initials: K
authors.lastname: Cohen
authors.forename: Francesca
authors.initials: F
authors.lastname: Conradie
authors.forename: Jennifer
authors.initials: J
authors.lastname: Zeinecker
authors.forename: Prudence
authors.initials: P
authors.lastname: Ive
authors.forename: Ian
authors.initials: I
authors.lastname: Sanne
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000382:microbiology; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000995:Antitubercular Agents / Q000008:administration & dosage*; D048588:Benzoxazines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003521:Cyclopropanes; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012293:Rifampin / Q000008:administration & dosage*; D013019:South Africa; D016896:Treatment Outcome; D014376:Tuberculosis / Q000150:complications* / Q000188:drug therapy
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; C098320:efavirenz; D012293:Rifampin