title: Long-term Prescription of Opioids and/or Benzodiazepines and Mortality Among HIV-Infected and Uninfected Patients.
abstract: BACKGROUND
  Increased long-term prescription of opioids and/or benzodiazepines necessitates evaluating risks associated with their receipt. We sought to evaluate the association between long-term opioids and/or benzodiazepines and mortality in HIV-infected patients receiving antiretroviral therapy and uninfected patients.
  
  
  METHODS
  Prospective analysis of all-cause mortality using multivariable methods and propensity score matching among HIV-infected patients receiving antiretroviral therapy and uninfected patients.
  
  
  RESULTS
  Of 64,602 available patients (16,989 HIV-infected and 47,613 uninfected), 27,128 (exposed and unexposed to long-term opioids and/or benzodiazepines) were 1:1 matched by propensity score. The hazard ratio for death was 1.40 [95% confidence interval (CI): 1.22 to 1.61] for long-term opioid receipt, 1.26 (95% CI: 1.08 to 1.48) for long-term benzodiazepine receipt, and 1.56 (95% CI: 1.26 to 1.92) for long-term opioid and benzodiazepine receipt. There was an interaction (P = 0.01) between long-term opioid receipt and HIV status with mortality. For long-term opioid receipt, the hazard ratio was 1.46 (95% CI: 1.15 to 1.87) among HIV-infected patients, and 1.25 (95% CI: 1.05 to 1.49) among uninfected patients. Mortality risk was increased for patients receiving both long-term opioids and benzodiazepines when opioid doses were ≥ 20 mg morphine-equivalent daily dose and for patients receiving long-term opioids alone when doses were ≥ 50 mg morphine-equivalent daily dose.
  
  
  CONCLUSIONS
  Long-term opioid receipt was associated with an increased risk of death; especially with long-term benzodiazepine receipt, higher opioid doses, and among HIV-infected patients. Long-term benzodiazepine receipt was associated with an increased risk of death regardless of opioid receipt. Strategies to mitigate risks associated with these medications, and caution when they are coprescribed, are needed particularly in HIV-infected populations.
authors.affiliation: *Yale University School of Medicine, New Haven, CT; †VA Connecticut Healthcare System, West Haven, CT; Departments of ‡Psychiatry; §Internal Medicine, Yale University School of Medicine, New Haven, CT; ‖Institute for Health, Health Care Policy, and Aging Research, Rutgers University, New Brunswick, NJ; ¶Center for Interdisciplinary Research on AIDS, Yale University School of Public Health, New Haven, CT; #Yale University School of Public Health, New Haven, CT; **Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA; ††VA Pittsburgh Healthcare System, Pittsburgh, PA; and ‡‡Pain Research, Informatics, Multi-morbidities and Education (PRIME) Center, VA Connecticut Healthcare System, West Haven, CT.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Weisberg
authors.forename: Kirsha S
authors.initials: KS
authors.lastname: Gordon
authors.forename: Declan T
authors.initials: DT
authors.lastname: Barry
authors.forename: William C
authors.initials: WC
authors.lastname: Becker
authors.forename: Stephen
authors.initials: S
authors.lastname: Crystal
authors.forename: Eva J
authors.initials: EJ
authors.lastname: Edelman
authors.forename: Julie
authors.initials: J
authors.lastname: Gaither
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Gordon
authors.forename: Joseph
authors.initials: J
authors.lastname: Goulet
authors.forename: Robert D
authors.initials: RD
authors.lastname: Kerns
authors.forename: Brent A
authors.initials: BA
authors.lastname: Moore
authors.forename: Janet
authors.initials: J
authors.lastname: Tate
authors.forename: Amy C
authors.initials: AC
authors.lastname: Justice
authors.forename: David A
authors.initials: DA
authors.lastname: Fiellin
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000627:therapeutic use*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D001569:Benzodiazepines / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis
chemical_list: D000701:Analgesics, Opioid; D044966:Anti-Retroviral Agents; D001569:Benzodiazepines