title: Hepatic safety and lack of antiretroviral interactions with buprenorphine/naloxone in HIV-infected opioid-dependent patients.
abstract: BACKGROUND
  The safety of buprenorphine/naloxone (bup/nx) in HIV-infected patients has not been established. Prior reports raise concern about hepatotoxicity and interactions with atazanavir.
  
  
  METHODS
  We conducted a prospective cohort study of 303 opioid-dependent HIV-infected patients initiating bup/nx treatment. We assessed changes in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) over time. We compared bup/nx doses in patients receiving the antiretroviral atazanavir to those not receiving atazanavir. We conducted surveillance for pharmacodynamic interactions.
  
  
  RESULTS
  Median AST [37.0 vs. 37.0 units/liter (U/L) respective interquartile ranges (IQRs) 26-53 and 26-59] and ALT (33.0 vs. 33.0 U/L, respective IQRs 19-50 and 18-50) values did not change over time among 141 patients comparing pre-bup/nx exposure with post-bup/nx exposure measures. During bup/nx exposure, 207 subjects demonstrated no significant change in median AST (36.0 vs. 35.0 U/L, respective IQRs 25-57 and 25-61) and ALT (29.0 vs. 31.0 U/L, respective IQRs 19-50 and 18-50) values collected a median of 6 months apart. Analyses restricted to patients with hepatitis C and HIV co-infection yielded similar results, except a small but significant decrease in first to last AST, during treatment with bup/nx (P = 0.048). Mean bup/nx dose, ranging 16.0-17.8 mg, did not differ over time or with co-administration of atazanavir. No pharmacodynamic interactions were noted.
  
  
  CONCLUSIONS
  Buprenorphine/naloxone did not produce measurable hepatic toxicity or pharmacodynamic interaction with atazanavir in HIV-infected opioid-dependent patients.
authors.affiliation: The CORE Center, Chicago, IL, USA. pvergara-rodriguez@corecenter.org
authors.forename: Pamela
authors.initials: P
authors.lastname: Vergara-Rodriguez
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Tozzi
authors.forename: Michael
authors.initials: M
authors.lastname: Botsko
authors.forename: Vijay
authors.initials: V
authors.lastname: Nandi
authors.forename: Frederick
authors.initials: F
authors.lastname: Altice
authors.forename: James E
authors.initials: JE
authors.lastname: Egan
authors.forename: Patrick G
authors.initials: PG
authors.lastname: O'Connor
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Sullivan
authors.forename: David A
authors.initials: DA
authors.lastname: Fiellin
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D000069446:Atazanavir Sulfate; D002047:Buprenorphine / Q000009:adverse effects* / Q000627:therapeutic use*; D000069479:Buprenorphine, Naloxone Drug Combination; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D009270:Naloxone / Q000009:adverse effects* / Q000627:therapeutic use*; D009842:Oligopeptides / Q000494:pharmacology; D009293:Opioid-Related Disorders / Q000150:complications* / Q000188:drug therapy; D011725:Pyridines / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D000069479:Buprenorphine, Naloxone Drug Combination; D009842:Oligopeptides; D011725:Pyridines; D009270:Naloxone; D002047:Buprenorphine; D000069446:Atazanavir Sulfate