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Does Antiretroviral Therapy Increase or Decrease the Risk of Cardiovascular Disease?

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Abstract

Atherosclerosis is a complex inflammatory process that has been identified as an important problem in persons with HIV infection. Epidemiologic studies have linked certain antiretroviral medications (some nucleoside reverse transcriptase inhibitors and protease inhibitors) with a higher risk of coronary heart disease (CHD). Conversely, nonnucleoside reverse transcriptase inhibitors, entry inhibitors, and integrase inhibitors appear neutral. HIV infection is a chronic inflammatory process associated with endothelial dysfunction, atherogenic dyslipidemia, and a higher risk for CHD. Initiation of antiretroviral therapy in the short term appears to lower CHD risk, regardless of the specific agents used. However, adequately powered randomized trials of antiretroviral therapy with CHD as a primary end point are lacking. Thus, the evidence of whether antiretroviral therapy increases or decreases CHD risk in persons with HIV is perplexing. This article reviews the current controversy of the role of HIV and antiretroviral therapy in the development of cardiovascular disease.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Henry K, Melroe H, Huebusch J, et al.: Severe premature coronary artery disease with protease inhibitors [letter]. Lancet 1998, 351:1328.

    Article  CAS  PubMed  Google Scholar 

  2. Marin B, Thiebaut R, Bucher HC, et al.: Non-AIDS-defining deaths and immunodeficiency in the era of combination antiretroviral therapy. AIDS 2009, 23:1743–1753.

    Article  PubMed  Google Scholar 

  3. Pallela FJ, Baker RK, Moorman AC, et al.: HIV Outpatient Study Investigators. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr 2006, 43:27–34.

    Article  Google Scholar 

  4. Strategies for Management of Antiretroviral Therapy (SMART) Study Group, El-Sadr WM, Lundgren JD, et al.: CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 2006, 355:2283–2296.

    Article  CAS  PubMed  Google Scholar 

  5. • Torriani FJ, Komarow L, Parker RA, et al. for the ACTG 5152s Study Team: Endothelial function in HIV-infected antiretroviral naïve subjects before and after starting potent antiretroviral therapy: AIDS Clinical Trials Group Study 5152s. J Am Coll Cardiol 2008, 52:569–576. This is a randomized clinical trial of persons initiating antiretroviral therapy with lopinavir-ritonavir, efavirenz, or the combination of the two evaluating endothelial function by brachial artery reactivity . All regimens improved endothelial function after 24 weeks, but it did not reach levels typically seen in HIV-uninfected persons.

    Article  CAS  PubMed  Google Scholar 

  6. •• D:A:D Study Group: Use of nucleoside-reverse transcriptase inhibitors and the risk of myocardial infarction in HIV infected patients enrolled in the D:A:D study: A multi-cohort collaboration. Lancet 2008, 371:1417–1426. This is a large, prospective, observational study of complications of HIV, demonstrating higher risk of MI with current use of abacavir or didanosine. The effect disappears 6 months after stopping drugs, and the biologic mechanism is unclear.

    Article  Google Scholar 

  7. Bozzette SA, Ake CF, Tam HK, et al.: Cardiovascular and cerebrovascular events in patients treated for human immunodeficiency virus infection. N Engl J Med 2003, 348:702–710.

    Article  CAS  PubMed  Google Scholar 

  8. Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study Group: Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med 2003, 349:1993–2003.

    Article  Google Scholar 

  9. Klein D, Hurley L, Queensbury C, Sidney S: Do protease inhibitors increase the risk for coronary heart disease in patients with HIV-1 infection? J Acquir Immune Defic Syndr 2002, 30:471–477.

    CAS  PubMed  Google Scholar 

  10. Mary-Krause M, Cotte L, Simon A, et al. and the Clinical Epidemiology Group from the French Hospital Database: Increased risk of myocardial infarction with duration of protease inhibitor therapy in HIV-infected men. AIDS 2003, 17:2479–2486.

    Article  PubMed  Google Scholar 

  11. Iloeje UH, Yuan Y, L’Italien GL, et al.: Protease inhibitor exposure and increased risk of cardiovascular disease in HIV-infected patients. HIV Med 2005, 6:37–44.

    Article  CAS  PubMed  Google Scholar 

  12. Friis-Møller N, Weber R, Reiss P, et al. for the DAD Study Group: Cardiovascular disease risk factors in HIV-infected persons--association with antiretroviral therapy. Results from the DAD study. AIDS 2003, 17:1179–1193.

    Article  PubMed  Google Scholar 

  13. D:A:D Study Group: Class of antiretroviral therapy and risk of myocardial infarction. N Engl J Med 2007, 356:1723–1735.

    Article  Google Scholar 

  14. Bozzette SA, Ake CF, Tam HK, et al.: Long-term survival and serious cardiovascular events in HIV-infected patients treated with highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2008, 47:338–341.

    Article  CAS  PubMed  Google Scholar 

  15. •• Worm SW, Sabin C, Weber R, et al.: Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. J Infect Dis 2010, 201:318–330. This is an updated report from the D:A:D study implicating abacavir, didanosine, lopinavir/ritonavir, and indinavir as specific antiretrovirals associated with a higher risk of MI.

    Article  CAS  PubMed  Google Scholar 

  16. Grinspoon S, Carr A: Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med 2005, 352:48–62.

    Article  CAS  PubMed  Google Scholar 

  17. Feingold KR, Krauss RM, Pang M, et al.: The hypertriglyceridemia of acquired immunodeficiency syndrome is associated with an increased prevalence of low density lipoprotein subclass pattern B. J Clin Endocrinol Metab 1993, 76:1423–1427.

    Article  CAS  PubMed  Google Scholar 

  18. Shor-Posner G, Basit A, Lu Y, et al.: Hypercholesterolemia is associated with immune dysfunction in early human immunodeficiency virus-1 infection. Am J Med 1993, 94:515–519.

    Article  CAS  PubMed  Google Scholar 

  19. Riddler SA, Smit E, Cole SR, et al.: Impact of HIV infection and HAART on serum lipids in men. JAMA 2003, 289:2978–2982.

    Article  CAS  PubMed  Google Scholar 

  20. Khovidhunkit W, Memon RA, Feingold KR, Grunfeld C: Infection and inflammation-induced proatherogenic changes of lipoproteins. J Infect Dis 2000, 181:S462–S472.

    Article  CAS  PubMed  Google Scholar 

  21. Hsue PY, Lo JC, Franklin A, et al.: Progression of atherosclerosis as assessed by carotid intima-media thickness in patients with HIV infection. Circulation 2004, 109:1603–1608.

    Article  PubMed  Google Scholar 

  22. Wohl DA, McComsey G, Tebas P, et al.: Current concepts in the diagnosis and management of metabolic complications of HIV and its therapy. Clin Infect Dis 2006, 43:645–653.

    Article  CAS  PubMed  Google Scholar 

  23. van Leth F, Phanuphak P, Stroes E, et al.: Nevirapine and efavirenz elicit different changes in lipid profiles in antiretroviral therapy-naive patients infected with HIV-1. Plos Med 2004, e19:64–74.

    Google Scholar 

  24. Gallant JE, Staszewski S, Pozniak AL, et al.: Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA 2004, 292:191–201.

    Article  CAS  PubMed  Google Scholar 

  25. Panel on Clinical Practices for Treatment of HIV Infection convened by the Department of Health and Human Services (DHHS): Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. December 1, 2009. http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.

  26. The SMART/INSIGHT and the D:A:D study groups: Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients. AIDS 2008, 22:F17–F24.

    Google Scholar 

  27. Cutrell A, Brothers D, Yeo J, et al.: Abacavir and the potential risk of myocardial infarction. Lancet 2008, 371:1413.

    Article  PubMed  Google Scholar 

  28. Benson C, Ribaudo H, Zheng E, et al.: No association of abacavir use with risk of mycocardial infarction or severe cardiovascular disease events: results from ACTG A5001 [abstract 721]. Proceedings of the 16th Conference on Retroviruses and Opportunistic Infections. Montreal, Canada; February 8–11, 2009.

  29. Gallant JE, Staszewski S, Pozniak AL, et al.; 903 Study Group: Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA 2004, 292:191–201.

    Article  CAS  PubMed  Google Scholar 

  30. • Hsue PY, Hunt PW, Wu Y, et al.: Association of abacavir and impaired endothelial function in treated and suppressed HIV-infected patients. AIDS 2009, 23:2021–2027. FMD was lower in the abacavir-treated patients (2.8% vs 4.9%, P = 0.01); cross-sectional analysis of nonrandomized subjects.

    Article  CAS  PubMed  Google Scholar 

  31. Shankar SS, Dube MP, Gorski JC, et al.: Indinavir impairs endothelial function in healthy HIV-negative men. Am Heart J 2005, 150:933.e1–933.e7.

    Article  Google Scholar 

  32. Lee GA, Seneviratne T, Noor MA, et al.: The metabolic effects of lopinavir/ritonavir in HIV-negative men. AIDS 2004, 18:641–649.

    Article  CAS  PubMed  Google Scholar 

  33. Noor A, Flint OP, Mae JF, Parker RA: Effects of atazanavir/ritonavir and lopinavir/ritonavir on glucose uptake and insulin sensitivity: demonstrable differences in vitro and clinically. AIDS 2006, 20:1813–1821.

    Article  CAS  PubMed  Google Scholar 

  34. •• Grinspoon SK, Grunfeld C, Kotler DP, et al.: State of the Science Conference: Initiative to Decrease Cardiovascular Risk and Increase Quality of Care for Patients Living With HIV/AIDS: Executive Summary. Circulation 2008, 118:198–210. This is the Executive Summary of the conference on the current state of the art of research on cardiovascular disease. Several associated articles discuss epidemiology, pathogenesis, and management.

    Article  PubMed  Google Scholar 

  35. Kitahata MM, Gange SJ, Abraham AG, et al.: Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med 2009, 361:822–824.

    Article  Google Scholar 

Download references

Acknowledgment

Funding was supported in part by a grant from the National Institute of Allergy and Infectious Diseases to the University of Cincinnati AIDS Clinical Trials Unit (U01-AI-069513-04).

Disclosure

Dr. Fichtenbaum receives grant support for research from Abbott Laboratories, Gilead Sciences, Tibotec, Advent, and Pfizer. He serves on the speakers’ bureau for Bristol-Myers Squibb.

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Authors and Affiliations

  1. Division of Infectious Diseases, University of Cincinnati College of Medicine, 231 Albert Sabin Way, PO Box 670560, Cincinnati, OH, 45267-0560, USA

    Carl J. Fichtenbaum

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Correspondence to Carl J. Fichtenbaum.

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Fichtenbaum, C.J. Does Antiretroviral Therapy Increase or Decrease the Risk of Cardiovascular Disease?. Curr HIV/AIDS Rep 7, 92–98 (2010). https://doi.org/10.1007/s11904-010-0045-5

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