title: Comparison of the risks of atherosclerotic events versus death from other causes associated with antiretroviral use.
abstract: BACKGROUND
  Studies considering the risk of atherosclerotic disease (AtD) associated with the use of HAART have reported inconsistent results.
  
  
  METHODS
  Data on antiretroviral therapy (ART) use, risk factors for cardiovascular disease (CVD), AtD and death from other causes in 18 603 HIV-infected patients from two established cohorts were evaluated. The relative hazards of AtD and death from other causes were calculated using a proportional hazards competing risks framework. The impact of protease inhibitor (PI)-containing, non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing or PI + NNRTI-containing regimens on these outcomes were compared to nucleoside reverse transcriptase inhibitor (NRTI)-only regimens or stopping therapy, adjusting for known CVD risk factors.
  
  
  RESULTS
  In 77 480 person-years of follow-up (median duration 3.49 years) there were 318 AtD events including 92 myocardial infarctions and 2044 deaths. Older age, hypertension, diabetes mellitus, having smoked and HIV disease stage were significantly associated with increased risk of AtD. PI- and NNRTI-containing regimens significantly reduced the joint risk of either AtD or death from other causes compared to NRTI-only or stopping therapy [hazard ratio (HR) for PI-containing ART, 0.76, 95% confidence interval (CI), 0.73-0.78, P< 0.001; NNRTI-containing ART, 0.69, 95% CI, 0.65-0.74; P< 0.001). PI-containing ART was associated with a borderline significant increased risk of myocardial infarction (cause-specific HR for PI-containing ART 1.19, 95% CI, 1.01-1.40, P = 0.04) but not with increased risk of AtD compared to NRTI-only regimens or stopping therapy (cause-specific HR for PI-containing ART, 1.03, 95% CI, 0.95-1.13, P = 0.44).
  
  
  CONCLUSIONS
  Overall benefits of PI- and NNRTI-based ART in reducing mortality significantly outweigh any risks of AtD in the "short-term" follow-up of this study. Traditional cardiac risk factors play an important role in determining AtD risk status.
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, UK.
authors.forename: Grace P S
authors.initials: GP
authors.lastname: Kwong
authors.forename: Azra C
authors.initials: AC
authors.lastname: Ghani
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rode
authors.forename: Lucy M
authors.initials: LM
authors.lastname: Bartley
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Cowling
authors.forename: Barbara
authors.initials: B
authors.lastname: da Silva
authors.forename: Christl A
authors.initials: CA
authors.lastname: Donnelly
authors.forename: Ard I
authors.initials: AI
authors.lastname: van Sighem
authors.forename: D William
authors.initials: DW
authors.lastname: Cameron
authors.forename: Sven A
authors.initials: SA
authors.lastname: Danner
authors.forename: Frank
authors.initials: F
authors.lastname: de Wolf
authors.forename: Roy M
authors.initials: RM
authors.lastname: Anderson
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D044966:Anti-Retroviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D050197:Atherosclerosis / Q000139:chemically induced* / Q000401:mortality; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking; D013997:Time Factors
chemical_list: D044966:Anti-Retroviral Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors