title: Risk of cardiovascular events associated with current exposure to HIV antiretroviral therapies in a US veteran population.
abstract: BACKGROUND
  To characterize the association of antiretroviral drug combinations on risk of cardiovascular events.
  
  
  METHODS
  Certain antiretroviral medications for human immunodeficiency virus (HIV) have been implicated in increasing risk of cardiovascular disease. However, antiretroviral drugs are typically prescribed in combination. We characterized the association of current exposure to antiretroviral drug combinations on risk of cardiovascular events including myocardial infarction, stroke, percutaneous coronary intervention, and coronary artery bypass surgery. We used the Veterans Health Administration Clinical Case Registry to analyze data from 24 510 patients infected with HIV from January 1996 through December 2009. We assessed the association of current exposure to 15 antiretroviral drugs and 23 prespecified combinations of agents on the risk of cardiovascular event by using marginal structural models and Cox models extended to accommodate time-dependent variables.
  
  
  RESULTS
  Over 164 059 person-years of follow-up, 934 patients had a cardiovascular event. Current exposure to abacavir, efavirenz, lamivudine, and zidovudine was significantly associated with increased risk of cardiovascular event, with odds ratios ranging from 1.40 to 1.53. Five combinations were significantly associated with increased risk of cardiovascular event, all of which involved lamivudine. One of these-efavirenz, lamivudine, and zidovudine-was the second most commonly used combination and was associated with a risk of cardiovascular event that is 1.60 times that of patients not currently exposed to the combination (odds ratio = 1.60, 95% confidence interval, 1.25-2.04).
  
  
  CONCLUSIONS
  In the VA cohort, exposure to both individual drugs and drug combinations was associated with modestly increased risk of a cardiovascular event.
authors.affiliation: Quantitative Sciences Unit, Center for Biomedical Informatics Research, Department of Medicine Division of Biostatistics, Department of Health Research & Policy, Stanford University.
authors.forename: Manisha
authors.initials: M
authors.lastname: Desai
authors.affiliation: VA Palo Alto Health Care System.
authors.forename: Vilija
authors.initials: V
authors.lastname: Joyce
authors.affiliation: Center for Primary Care and Outcomes Research, and Center for Health Policy Division of General Medical Disciplines, Department of Medicine.
authors.forename: Eran
authors.initials: E
authors.lastname: Bendavid
authors.affiliation: Division of Biostatistics, Department of Health Research & Policy, Stanford University.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Olshen
authors.affiliation: Division of Health Policy, Department of Health Research & Policy, Stanford University, Stanford, California.
authors.forename: Mark
authors.initials: M
authors.lastname: Hlatky
authors.affiliation: VA Palo Alto Health Care System.
authors.forename: Adam
authors.initials: A
authors.lastname: Chow
authors.affiliation: VA Palo Alto Health Care System.
authors.forename: Mark
authors.initials: M
authors.lastname: Holodniy
authors.affiliation: VA Palo Alto Health Care System.
authors.forename: Paul
authors.initials: P
authors.lastname: Barnett
authors.affiliation: VA Palo Alto Health Care System Center for Primary Care and Outcomes Research, and Center for Health Policy.
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Owens
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D014481:United States / Q000453:epidemiology; D014728:Veterans / Q000706:statistics & numerical data*
chemical_list: D044966:Anti-Retroviral Agents
keywords: HIV; antiretroviral therapy; cardiovascular event; myocardial infarction