title: Use of Abacavir and Risk of Cardiovascular Disease Among HIV-Infected Individuals.
abstract: BACKGROUND
  Evidence is conflicting about the association of abacavir use and cardiovascular disease (CVD) among HIV-infected individuals. Previous studies may have been biased by the preferential initiation or continuation of abacavir in patients with renal dysfunction.
  
  
  METHODS
  We conducted a cohort study in Kaiser Permanente California during 1998-2011, following HIV-infected adults initiating antiretroviral therapy until the earliest of CVD (ie, coronary heart disease or ischemic stroke), health plan disenrollment, death, or end of study. We used inverse-probability weighting to fit marginal structural models to estimate hazard ratios (HRs) for CVD comparing regimens with and without abacavir. Propensity score models included demographics, HIV-specific factors, and CVD risk factors, including alcohol/drug use, smoking, overweight/obesity, diabetes, lipid-lowering and hypertension therapy, and renal dysfunction (ie, estimated glomerular filtration rate <60 mL·min·1.73 m).
  
  
  RESULTS
  Among 8154 subjects, 178 had ≥1 CVD event, with 24/704 (3.4%) in the abacavir group and 154/7450 (2.1%) in the group initiating regimens without abacavir. Abacavir users had more renal dysfunction at antiretroviral therapy initiation (7.0% vs. 3.3%, P < 0.001). Compared with patients initiating regimens without abacavir, abacavir users had a 2.2-fold higher risk of CVD in intention-to-treat analysis [HR 2.2, 95% confidence interval (CI): 1.4 to 3.5], a 2.7-fold higher risk when remaining on their initial regimens for ≥1 year (HR 2.7, 95% CI: 1.5 to 5.0), and a 2.1-fold higher risk in per-protocol analysis (HR 2.1, 95% CI: 0.9 to 5.0).
  
  
  CONCLUSIONS
  Abacavir was associated with an over 2-fold increased risk of CVD, which was not explained by renal dysfunction or other CVD risk factors.
authors.affiliation: *Division of Research, Kaiser Permanente Northern California, Oakland, CA; †Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA; ‡San Leandro Medical Center, Kaiser Permanente Northern California, Hayward, CA; §Los Angeles Medical Center, Kaiser Permanente Southern California, Los Angeles, CA; and ‖Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville, MD.
authors.forename: Julia L
authors.initials: JL
authors.lastname: Marcus
authors.forename: Romain S
authors.initials: RS
authors.lastname: Neugebauer
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Leyden
authors.forename: Chun R
authors.initials: CR
authors.lastname: Chao
authors.forename: Lanfang
authors.initials: L
authors.lastname: Xu
authors.forename: Charles P
authors.initials: CP
authors.lastname: Quesenberry
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Klein
authors.forename: William J
authors.initials: WJ
authors.lastname: Towner
authors.forename: Michael A
authors.initials: MA
authors.lastname: Horberg
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Silverberg
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D002140:California / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D015224:Dideoxynucleosides / Q000009:adverse effects* / Q000627:therapeutic use*; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D008875:Middle Aged; D012307:Risk Factors; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D000099227:Abacavir