title: Risk of cardiovascular disease from antiretroviral therapy for HIV: a systematic review.
abstract: BACKGROUND
  Recent studies suggest certain antiretroviral therapy (ART) drugs are associated with increases in cardiovascular disease.
  
  
  OBJECTIVE
  We performed a systematic review and meta-analysis to summarize the available evidence, with the goal of elucidating whether specific ART drugs are associated with an increased risk of myocardial infarction (MI).
  
  
  METHODS
  We searched Medline, Web of Science, the Cochrane Library, and abstract archives from the Conference on Retroviruses and Opportunistic Infections and International AIDS Society up to June 2011 to identify published articles and abstracts.
  
  
  METHODS
  Eligible studies were comparative and included MI, strokes, or other cardiovascular events as outcomes.
  
  
  METHODS
  Eligibility screening, data extraction, and quality assessment were performed independently by two investigators.
  
  
  RESULTS
  Random effects methods and Fisher's combined probability test were used to summarize evidence.
  
  
  RESULTS
  Twenty-seven studies met inclusion criteria, with 8 contributing to a formal meta-analysis. Findings based on two observational studies indicated an increase in risk of MI for patients recently exposed (usually defined as within last 6 months) to abacavir (RR 1.92, 95% CI 1.51-2.42) and protease inhibitors (PI) (RR 2.13, 95% CI 1.06-4.28). Our analysis also suggested an increased risk associated with each additional year of exposure to indinavir (RR 1.11, 95% CI 1.05-1.17) and lopinavir (RR 1.22, 95% CI 1.01-1.47). Our findings of increased cardiovascular risk from abacavir and PIs were in contrast to four published meta-analyses based on secondary analyses of randomized controlled trials, which found no increased risk from cardiovascular disease.
  
  
  CONCLUSIONS
  Although observational studies implicated specific drugs, the evidence is mixed. Further, meta-analyses of randomized trials did not find increased risk from abacavir and PIs. Our findings that implicate specific ARTs in the observational setting provide sufficient evidence to warrant further investigation of this relationship in studies designed for that purpose.
authors.affiliation: Center for Primary Care and Outcomes Research, and Center for Health Policy, Stanford University, Stanford, California, United States of America. claybavinger@gmail.com
authors.forename: Clay
authors.initials: C
authors.lastname: Bavinger
authors.forename: Eran
authors.initials: E
authors.lastname: Bendavid
authors.forename: Katherine
authors.initials: K
authors.lastname: Niehaus
authors.forename: Richard A
authors.initials: RA
authors.lastname: Olshen
authors.forename: Ingram
authors.initials: I
authors.lastname: Olkin
authors.forename: Vandana
authors.initials: V
authors.lastname: Sundaram
authors.forename: Nicole
authors.initials: N
authors.lastname: Wein
authors.forename: Mark
authors.initials: M
authors.lastname: Holodniy
authors.forename: Nanjiang
authors.initials: N
authors.lastname: Hou
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Owens
authors.forename: Manisha
authors.initials: M
authors.lastname: Desai
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D006801:Humans; D011480:Protease Inhibitors / Q000009:adverse effects; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects; D012306:Risk
chemical_list: D019380:Anti-HIV Agents; D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors
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