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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.

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.

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  • Authors+Show Affiliations

    ,

    Center for Primary Care and Outcomes Research, and Center for Health Policy, Stanford University, Stanford, California, United States of America. claybavinger@gmail.com

    , , , , , , , , ,

    Source

    PloS one 8:3 2013 pg e59551

    MeSH

    Anti-HIV Agents
    Cardiovascular Diseases
    Humans
    Protease Inhibitors
    Reverse Transcriptase Inhibitors
    Risk

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, Non-P.H.S.
    Review
    Systematic Review

    Language

    eng

    PubMed ID

    23555704

    Citation

    Bavinger, Clay, et al. "Risk of Cardiovascular Disease From Antiretroviral Therapy for HIV: a Systematic Review." PloS One, vol. 8, no. 3, 2013, pp. e59551.
    Bavinger C, Bendavid E, Niehaus K, et al. Risk of cardiovascular disease from antiretroviral therapy for HIV: a systematic review. PLoS ONE. 2013;8(3):e59551.
    Bavinger, C., Bendavid, E., Niehaus, K., Olshen, R. A., Olkin, I., Sundaram, V., ... Desai, M. (2013). Risk of cardiovascular disease from antiretroviral therapy for HIV: a systematic review. PloS One, 8(3), pp. e59551. doi:10.1371/journal.pone.0059551.
    Bavinger C, et al. Risk of Cardiovascular Disease From Antiretroviral Therapy for HIV: a Systematic Review. PLoS ONE. 2013;8(3):e59551. PubMed PMID: 23555704.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Risk of cardiovascular disease from antiretroviral therapy for HIV: a systematic review. AU - Bavinger,Clay, AU - Bendavid,Eran, AU - Niehaus,Katherine, AU - Olshen,Richard A, AU - Olkin,Ingram, AU - Sundaram,Vandana, AU - Wein,Nicole, AU - Holodniy,Mark, AU - Hou,Nanjiang, AU - Owens,Douglas K, AU - Desai,Manisha, Y1 - 2013/03/26/ PY - 2012/08/03/received PY - 2013/02/19/accepted PY - 2013/4/5/entrez PY - 2013/4/5/pubmed PY - 2013/10/1/medline SP - e59551 EP - e59551 JF - PloS one JO - PLoS ONE VL - 8 IS - 3 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23555704/full_citation L2 - http://dx.plos.org/10.1371/journal.pone.0059551 DB - PRIME DP - Unbound Medicine ER -