HIV-Infektion und Lipidentgleisung — Gründe und Gegenmaßnahmen

Kardiovaskuläre Erkrankungen

HIV and dyslipidemia - reasons and therapy

Die Infektion mit dem Humanen Immundefizienz-Virus (HIV) führt zu einer bedeutenden Erhöhung des kardiovaskulären Risikos. Im folgenden CME-Kurs erfahren Sie, warum das so ist, und welche therapeutischen Maßnahmen erforderlich sind, um HIV-Patienten möglichst optimal vor kardiovaskulären Ereignissen zu schützen.

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Literatur

  1. 1.

    Palella FJ, Delaney KM, Moorman AC et al. Declining Morbidity and Mortality among Patients with Advanced Human Immunodefciency Virus Infection. New England Journal of Medicine. 1998;338:853–60.

    PubMed  Google Scholar 

  2. 2.

    Collaboration TATAC. HIV treatment response and prognosis in Europe and North America in the frst decade of highly active antiretroviral therapy: a collaborative analysis. The Lancet. 2006;368(9534):451–8.

    Google Scholar 

  3. 3.

    Samji H, Cescon A, Hogg RS et al. Closing the Gap: Increases in Life Expectancy among Treated HIV-Positive Individuals in the United States and Canada. PLoS ONE. 2013;8(12):e81355.

    PubMed  PubMed Central  Google Scholar 

  4. 4.

    Shah ASV, Stelzle D, Lee KK et al. Global Burden of Atherosclerotic Cardiovascular Disease in People Living With HIV. Circulation. 2018;138:1100–12.

    PubMed  PubMed Central  Google Scholar 

  5. 5.

    Alonso A, Barnes AE, Guest JL, Shah A, Shao IY, Marconi V. HIV Infection and Incidence of Cardiovascular Diseases: An Analysis of a Large Healthcare Database. Journal of the American Heart Association. 2019;8(14):e012241.

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    Feinstein MJ, Bahiru E, Achenbach C et al. Patterns of Cardiovascular Mortality for HIV-Infected Adults in the United States: 1999 to 2013. The American Journal of Cardiology. 2016;117:214–20.

    PubMed  Google Scholar 

  7. 7.

    Marincowitz C, Genis A, Goswami N, De Boever P, Nawrot TS, Strijdom H. Vascular endothelial dysfunction in the wake of HIV and ART. The FEBS J. 2019;286:1256–70.

    CAS  PubMed  Google Scholar 

  8. 8.

    Calmy A, Gayet-Ageron A, Montecucco F et al. HIV increases markers of cardiovascular risk: results from a randomized, treatment interruption trial. AIDS. 2009;23:929–39.

    CAS  PubMed  Google Scholar 

  9. 9.

    Grunfeld C, Pang M, Doerrler W, Shigenaga JK, Jensen P, Feingold KR. Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodefciency virus infection and the acquired immunodefciency syndrome. 1992;74:1045–52.

    CAS  Google Scholar 

  10. 10.

    Mujawar Z, Rose H, Morrow MP et al. Human Immunodefciency Virus Impairs Reverse Cholesterol Transport from Macrophages. PLoS Biology. 2006;4:e365.

    PubMed  PubMed Central  Google Scholar 

  11. 11.

    Brath H, Grabovac I, Schalk H, Degen O, Dorner TE. Prevalence and Correlates of Smoking and Readiness to Quit Smoking in People Living with HIV in Austria and Germany. 2016;11:e0150553.

    Google Scholar 

  12. 12.

    Rasmussen LD, Helleberg M, May MT et al. Myocardial Infarction Among Danish HIV-Infected Individuals: Population-Attributable Fractions Associated With Smoking. Clin Infect Dis. 2015;60:1415–23.

    PubMed  Google Scholar 

  13. 13.

    Helleberg M, Afzal S, Kronborg G et al. Mortality Attributable to Smoking Among HIV-1—Infected Individuals: A Nationwide, Population-Based Cohort Study. Clin Infect Dis. 2013;56:727–34.

    PubMed  Google Scholar 

  14. 14.

    Joy T, Keogh HM, Hadigan C et al. Dietary fat intake and relationship to serum lipid levels in HIV-infected patients with metabolic abnormalities in the HAART era. 2007;21(12):1591–1600.

    CAS  Google Scholar 

  15. 15.

    Lai S, Fishman EK, Lai H et al. Long-Term Cocaine Use and Antiretroviral Therapy Are Associated with Silent Coronary Artery Disease in African Americans with HIV Infection Who Have No Cardiovascular Symptoms. Clin Infect Dis. 2008;46:600–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Lorenz DR, Dutta A, Mukerji SS, Holman A, Uno H, Gabuzda D. Marijuana Use Impacts Midlife Cardiovascular Events in HIV-Infected Men. Clin Infect Dis. 2017;65:626–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Group TDCoAEoA-HDDS. Combination Antiretroviral Therapy and the Risk of Myocardial Infarction. N Engl J Med. 2003;349:1993–2003.

    Google Scholar 

  18. 18.

    Group TDS. Class of Antiretroviral Drugs and the Risk of Myocardial Infarction. N Engl J Med. 2007;356:1723–35.

    Google Scholar 

  19. 19.

    Kaplan RC, Kingsley LA, Sharrett AR et al. Ten-Year Predicted Coronary Heart Disease Risk in HIV-Infected Men and Women. Clin Infect Dis. 2007;45:1074–81.

    PubMed  Google Scholar 

  20. 20.

    Stein JH, Hsue PY. Infammation, Immune Activation, and CVD Risk in Individuals With HIV Infection. JAMA. 2012;308:405.

    CAS  PubMed  Google Scholar 

  21. 21.

    Hadigan C, Meigs JB, Wilson PWF et al. Prediction of Coronary Heart Disease Risk in HIV-Infected Patients with Fat Redistribution. Clin Infect Dis. 2003;36:909–16.

    PubMed  Google Scholar 

  22. 22.

    Worm SW, Friis-Møller N, Bruyand M et al. High prevalence of the metabolic syndrome in HIV-infected patients: impact of different defnitions of the metabolic syndrome. AIDS. 2010;24:427–35.

    PubMed  Google Scholar 

  23. 23.

    Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased Acute Myocardial Infarction Rates and Cardiovascular Risk Factors among Patients with Human Immunodefciency Virus Disease. Clin Endocrinol Metab. 2007;92:2506–12.

    CAS  Google Scholar 

  24. 24.

    Carr A, Samaras K, Burton S et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS. 1998;12:F51–F58.

    CAS  PubMed  Google Scholar 

  25. 25.

    Group TSfMoATSS. CD4+ Count—Guided Interruption of Antiretroviral Treatment. N Engl J of Med. 2006;355:2283–96.

    Google Scholar 

  26. 26.

    Marcus JL, Neugebauer RS, Leyden WA et al. Use of Abacavir and Risk of Cardiovascular Disease Among HIV-Infected Individuals. J Acquir Immune Defc Syndr. 2016;71:413–9.

    CAS  Google Scholar 

  27. 27.

    Strategies for Management of Anti-Retroviral Therapy I, Groups DADS. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients. AIDS. 2008;22:F17–F24.

    Google Scholar 

  28. 28.

    Panel EM. EACS Guidelines Version 10.0. Practice Guideline. 2019.

    Google Scholar 

  29. 29.

    Cid-Silva P, Fernández-Bargiela N, Margusino-Framiñán L et al. Treatment with tenofovir alafenamide fumarate worsens the lipid profle of HIV-infected patients versus treatment with tenofovir disoproxil fumarate, each coformulated with elvitegravir, cobicistat, and emtricitabine. Basic Clin Pharmacol Toxicol. 2019;124:479–90.

    CAS  PubMed  Google Scholar 

  30. 30.

    Gallant JE, Daar ES, Raf F et al. Efcacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate given as fxed-dose combinations containing emtricitabine as backbones for treatment of HIV-1 infection in virologically suppressed adults: a randomised, double-blind, activ. The Lancet HIV. 2016;3:e158–e165.

    PubMed  Google Scholar 

  31. 31.

    Wohl D, Oka S, Clumeck N et al. Brief Report: A Randomized, Double-Blind Comparison of Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate, Each Coformulated With Elvitegravir, Cobicistat, and Emtricitabine for Initial HIV-1 Treatment: Week 96 Results. J Acquir Immune Defc Syndr. 2016;72:58–64.

    CAS  Google Scholar 

  32. 32.

    Gebhardt A, Fichtenbaum CJ. Current pharmacotherapy for the treatment of dyslipidemia associated with HIV infection. Expert Opin Pharmacother. 2019;20:1719–29.

    PubMed  Google Scholar 

  33. 33.

    Ryom L, Lundgren JD, El-Sadr W et al. Cardiovascular disease and use of contemporary protease inhibitors: the D:A:D international prospective multicohort study. The Lancet HIV. 2018;5:e291–e300.

    PubMed  Google Scholar 

  34. 34.

    Stein JH, Ribaudo HJ, Hodis HN et al. A prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness. AIDS. 2015;29:1775–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Lafeur J, Bress AP, Rosenblatt L et al. Cardiovascular outcomes among HIV-infected veterans receiving atazanavir. AIDS. 2017;31:2095–106.

    Google Scholar 

  36. 36.

    Tebas P, Sension M, Arribas J et al. Lipid Levels and Changes in Body Fat Distribution in Treatment-Naive, HIV-1—Infected Adults Treated With Rilpivirine or Efavirenz for 96 Weeks in the ECHO and THRIVE Trials. Clin Infect Dis. 2014;59:425–34.

    CAS  PubMed  Google Scholar 

  37. 37.

    Molina J-M, Squires K, Sax PE et al. Doravirine versus ritonavirboosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 48-week results of a randomised, doubleblind, phase 3, non-inferiority trial. The Lancet HIV. 2018;5:e211–e220.

    PubMed  Google Scholar 

  38. 38.

    Ciaf L, Cavassini M, Genne D et al. Switch to etravirine for HIVpositive patients receiving statin treatment: a prospective study. Eur J Clin Invest. 2015;45:720–30.

    Google Scholar 

  39. 39.

    Ofotokun I, Na LH, Landovitz RJ et al. Comparison of the Metabolic Efects of Ritonavir-Boosted Darunavir or Atazanavir Versus Raltegravir, and the Impact of Ritonavir Plasma Exposure: ACTG 5257. Clin Infect Dis. 2015;60:1842–51.

    PubMed  PubMed Central  Google Scholar 

  40. 40.

    Fung HB, Guo Y. Enfuvirtide: A fusion inhibitor for the treatment of HIV infection. Clin Ther. 2004;26:352–78.

    CAS  PubMed  Google Scholar 

  41. 41.

    Daar ES, Dejesus E, Ruane P et al. Efcacy and safety of switching to fxed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1: 48 week results of a randomised, open-label, multicentre, ph. The Lancet HIV. 2018;5:e347–e356.

    PubMed  Google Scholar 

  42. 42.

    Martínez E, Larrousse M, Llibre JM et al. Substitution of raltegravir for ritonavir-boosted protease inhibitors in HIV-infected patients: the SPIRAL study. AIDS. 2010;24:1697–1707.

    PubMed  Google Scholar 

  43. 43.

    Gatell JM, Assoumou L, Moyle G et al. Immediate Versus Deferred Switching From a Boosted Protease Inhibitor—based Regimen to a Dolutegravir-based Regimen in Virologically Suppressed Patients With High Cardiovascular Risk or Age ≥50 Years: Final 96-Week Results of the NEAT022 Study. Clin Infect Dis. 2019;68:597–606.

    CAS  PubMed  Google Scholar 

  44. 44.

    Bourgi K, Rebeiro PF, Turner M et al. Greater Weight Gain in Treatment Naïve Persons Starting Dolutegravir-Based Antiretroviral Therapy. Clin Infect Dis. 2020;70:1267–74.

    CAS  PubMed  Google Scholar 

  45. 45.

    Grunfeld C. Dyslipidemia and its Treatment in HIV Infection. Top HIV Med. 2010;18:112–8.

    PubMed  PubMed Central  Google Scholar 

  46. 46.

    Macinnes A, Lazzarin A, Di Perri G et al. Maraviroc Can Improve Lipid Profles in Dyslipidemic Patients with HIV: Results from the MERIT Trial. HIV Clin Trials. 2011;12:24–36.

    CAS  PubMed  Google Scholar 

  47. 47.

    Mach F, Baigent C, Catapano AL et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modifcation to reduce cardiovascular risk. Eur Heart J. 2020;41:111–88.

    PubMed  Google Scholar 

  48. 48.

    Aberg JA, Gallant JE, Ghanem KG, Emmanuel P, Zingman BS, Horberg MA. Primary Care Guidelines for the Management of Persons Infected With HIV: 2013 Update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014;58:1–10.

    Google Scholar 

  49. 49.

    Zanetti HR, Gonçalves A, Teixeira Paranhos Lopes L et al. Efects of Exercise Training and Statin Use in People Living with Human Immunodefciency Virus with Dyslipidemia. Medicine and science in sports and exercise. Med Sci Sports Exerc. 2020;52:16–24.

    PubMed  Google Scholar 

  50. 50.

    Lazzaretti RK, Kuhmmer R, Sprinz E, Polanczyk CA, Ribeiro JP. Dietary Intervention Prevents Dyslipidemia Associated With Highly Active Antiretroviral Therapy in Human Immunodefciency Virus Type 1—Infected Individuals. J Am Coll Cardiol. 2012;59:979–88.

    CAS  PubMed  Google Scholar 

  51. 51.

    Gutierrez MDM, Mateo MG, Corbacho N, Vidal F, Domingo P. Drug-drug interactions when treating HIV-related metabolic disorders. Expert Opinion on Drug Metabolism & Toxicology. 2019:1–16.

    Google Scholar 

  52. 52.

    Gerber JG, Rosenkranz SL, Fichtenbaum CJ et al. Efect of efavirenz on the pharmacokinetics of simvastatin, atorvastatin, and pravastatin: results of AIDS Clinical Trials Group 5108 Study. J Acquir Immune Defc Syndr. 2005;39:307–12.

    CAS  Google Scholar 

  53. 53.

    Kakuda TN, Schöller-Gyüre M, Hoetelmans RMW. Pharmacokinetic Interactions between Etravirine and Non-Antiretroviral Drugs. Clin Pharmacokinet. 2011 Jan;50:25–39.

    CAS  PubMed  Google Scholar 

  54. 54.

    Erlandson KM, Jiang Y, Debanne SM, McComsey GA. Rosuvastatin Worsens Insulin Resistance in HIV-Infected Adults on Antiretroviral Therapy. Clin Infect Dis. 2015; 61: 1566–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Khalilieh S, Yee KL, Sanchez RI et al. Results of a doravirineatorvastatin drug-drug interaction study. 2016:AAC.01364–01316.

  56. 56.

    van Luin M, Colbers A, van Ewijk-Beneken Kolmer EWJ et al. Drug-drug interactions between raltegravir and pravastatin in healthy volunteers. J Acquir Immune Defc Syndr. 2010;55:82–6.

    Google Scholar 

  57. 57.

    Negredo E, Moltó J, Puig J et al. Ezetimibe, a promising lipid-lowering agent for the treatment of dyslipidaemia in HIV-infected patients with poor response to statins. AIDS. 2006;20(17):2159–64.

    CAS  PubMed  Google Scholar 

  58. 58.

    Laufs U, Parhofer KG, Ginsberg HN, Hegele RA. Clinical review on triglycerides. Eur Heart J. 2020;41:99–109c.

    PubMed  Google Scholar 

  59. 59.

    Feinstein MJ, Hsue PY, Benjamin LA et al. Characteristics, Prevention, and Management of Cardiovascular Disease in People Living With HIV: A Scientifc Statement From the American Heart Association. Circulation. 2019;140(2):e98–e124.

    CAS  PubMed  Google Scholar 

  60. 60.

    Amend KL, Landon J, Thyagarajan V, Niemcryk S, McAfee A. Incidence of Hospitalized Rhabdomyolysis with Statin and Fibrate Use in an Insured US Population. Ann Pharmacother. 2011;45:1230–9.

    PubMed  Google Scholar 

  61. 61.

    Longenecker CT et al. Statins to improve cardiovascular outcomes in treated HIV infection. Curr Opin Infect Dis. 2016;29:1–9

    CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Dr. med. Ursula Kassner.

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Hollstein, T., Schumann, F. & Kassner, U. HIV-Infektion und Lipidentgleisung — Gründe und Gegenmaßnahmen. MMW - Fortschritte der Medizin 162, 54–61 (2020). https://doi.org/10.1007/s15006-020-0015-9

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Keywords

  • HIV infection
  • risk for cardiovascular disease
  • lipid abnormalities
  • inflammation
  • lipid lowering therapy