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Risk of Cardiovascular Disease from Antiretroviral Therapy for HIV: A Systematic Review

Author

Listed:
  • Clay Bavinger
  • Eran Bendavid
  • Katherine Niehaus
  • Richard A Olshen
  • Ingram Olkin
  • Vandana Sundaram
  • Nicole Wein
  • Mark Holodniy
  • Nanjiang Hou
  • Douglas K Owens
  • Manisha Desai

Abstract

Background: Recent studies suggest certain antiretroviral therapy (ART) drugs are associated with increases in cardiovascular disease. Purpose: 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). Data Sources: 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. Study Selection: Eligible studies were comparative and included MI, strokes, or other cardiovascular events as outcomes. Data Extraction: Eligibility screening, data extraction, and quality assessment were performed independently by two investigators. Data Synthesis: Random effects methods and Fisher’s combined probability test were used to summarize evidence. Findings: 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. Conclusion: 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.

Suggested Citation

  • Clay Bavinger & Eran Bendavid & Katherine Niehaus & Richard A Olshen & Ingram Olkin & Vandana Sundaram & Nicole Wein & Mark Holodniy & Nanjiang Hou & Douglas K Owens & Manisha Desai, 2013. "Risk of Cardiovascular Disease from Antiretroviral Therapy for HIV: A Systematic Review," PLOS ONE, Public Library of Science, vol. 8(3), pages 1-14, March.
    • Handle: RePEc:plo:pone00:0059551
    DOI: 10.1371/journal.pone.0059551
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    References listed on IDEAS

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    1. Viechtbauer, Wolfgang, 2010. "Conducting Meta-Analyses in R with the metafor Package," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 36(i03).
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    1. Yongling Xiao & Michal Abrahamowicz & Erica E. M. Moodie & Rainer Weber & James Young, 2014. "Flexible Marginal Structural Models for Estimating the Cumulative Effect of a Time-Dependent Treatment on the Hazard: Reassessing the Cardiovascular Risks of Didanosine Treatment in the Swiss HIV Coho," Journal of the American Statistical Association, Taylor & Francis Journals, vol. 109(506), pages 455-464, June.
    2. Pierre Gantner & Firouze Bani-Sadr & Rodolphe Garraffo & Pierre-Marie Roger & Michèle Treger & Thomas Jovelin & Pascal Pugliese & David Rey & Dat’AIDS cohort, 2016. "Switch to Ritonavir-Boosted versus Unboosted Atazanavir plus Raltegravir Dual-Drug Therapy Leads to Similar Efficacy and Safety Outcomes in Clinical Practice," PLOS ONE, Public Library of Science, vol. 11(10), pages 1-13, October.
    3. Parveen Kumar & Christophe Arendt & Simon Martin & Safaa Al Soufi & Philipp DeLeuw & Eike Nagel & Valentina O. Puntmann, 2023. "Multimodality Imaging in HIV-Associated Cardiovascular Complications: A Comprehensive Review," IJERPH, MDPI, vol. 20(3), pages 1-18, January.

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