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Lipid Metabolism and Cardiovascular Risk in HIV-1 Infection and HAART: Present and Future Problems

By Sara Melzi, Laura Carenzi, Maria Vittoria Cossu, Simone Passerini, Amedeo Capetti and Giuliano Rizzardini


Many infections favor or are directly implicated with lipid metabolism perturbations and/or increased risk of coronary heart disease (CHD). HIV itself has been shown to increase lipogenesis in the liver and to alter the lipid profile, while the presence of unsafe habits, addiction, comorbidities, and AIDS-related diseases increases substantially the risk of cardiovascular disease (CVD) in the HIV-infected population. Antiretroviral therapy reduces such stimuli but many drugs have intrinsic toxicity profiles impacting on metabolism or potential direct cardiotoxicity. In a moment when the main guidelines of HIV therapy are predating the point when to start treating, we mean to highlight the contribution of HIV-1 to lipid alteration and inflammation, the impact of antiretroviral therapy, the decisions on what drugs to use to reduce the probability of having a cardiovascular event, the increasing use of statins and fibrates in HIV-1 infected subjects, and finally the switch strategies, that balance effectiveness and toxicity to move the decision to change HIV drugs. Early treatment might reduce the negative effect of HIV on overall cardiovascular risk but may also evidence the impact of drugs, and the final balance (reduction or increase in CHD and lipid abnormalities) is not known up to date

Topics: Review Article
Publisher: Hindawi Publishing Corporation
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Provided by: PubMed Central

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  1. (2005). A randomized trial of the efficacy and safety of fenofibrate versus pravastatin in HIV-infected subjects with lipid abnormalities:
  2. (2009). A simplification trial switching from nucleoside reverse transcriptase inhibitors to once-daily fixed-dose abacavir/lamivudine or tenofovir/ emtricitabine in HIV-1-infected patients with virological suppression,”
  3. (2010). Abacavir and cardiovascular risk,” Current Opinion
  4. (2009). Abacavir-lamivudine versus tenofovir-emtricitabine for initial HIV-1
  5. (2003). Aberg et al., “Guidelines for the evaluation and management of dyslipidemia in human immunodeficiency virus (HIV)-infected adults receiving antiretroviral therapy:
  6. (2001). andB.G.Gazzard,“Dietaryadvicewithorwithoutpravastatin for the management of hypercholesterolaemia associated with protease inhibitor therapy,”
  7. (2001). Antiretroviral treatment simplification with nevirapine in protease inhibitor— experienced patients with HIV-associated lipodystrophy: 1-year prospective follow-up of a multicenter, randomized, controlled study,”
  8. (2008). Arribas L´ opez, “Secondary effects of treatment with maraviroc and other CCR5 antagonists.
  9. (2008). Cˆ ot´ e et al., “Changes in metabolic toxicity after switching from stavudine/didanosine to tenofovir/lamivudine—a staccato trial substudy,”
  10. (2008). Cardiovascular risk score change in HIV-1-infected patients switched to an atazanavir-based
  11. (2010). Change to atazanavir/ritonavir treatment improves lipids but not endothelial function in patients on stable antiretroviral therapy,”
  12. (2008). Changes in markers of atherogenic dyslipidemia, inflammation, and platelet activation with treatment with pravastatin, fenofi-brate, or the combination: results from ACTG
  13. (1997). Chronic infections and coronary heart disease: is there a link?”
  14. (2009). Collot-Teixeira et al., “Prevention of atherosclerosis in patients living
  15. (2003). Comparison of metabolic abnormalities 48 weeks after switching from highly active antiretroviral therapy containing a non-nucleoside reverse transcriptase inhibitor to Trizivir versus continued highly active antiretroviral therapy,”
  16. (2003). Comparison of metabolic abnormalities and clinical lipodystrophy 48 weeks after switching from HAART to Trizivir versus continued HAART: the trizal study,” HIV Clinical Trials,v o l .4 ,n o .1 ,p p .
  17. (2009). D.Cooper,M.Bloch,A.Humphriesetal.,“Simplificationwith fixed-dose Tenofovir/Emtricitabine or Abacavir/Lamivudine in adults with suppressed HIV replication: the STEAL study, a randomized, open-label, 96-week, non-inferiority trial,”
  18. (2008). Drug/drug interaction between lopinavir/ritonavir and rosuvastatin in healthy volunteers,”
  19. (2005). Dyslipidemia in HIV patients,”
  20. (2008). E.Ribera,J .C.P aradi˜ neiro,A.Curranetal.,“Improvementsin subcutaneous fat, lipid profile, and parameters of mitochondrial toxicity in patients with peripheral lipoatrophy when stavudine is switched to tenofovir
  21. (2007). Efavirenz to nevirapine switch in HIV-1—infected patients with dyslipidemia: a randomized, controlled study,”
  22. (2009). Effect of atazanavir versus other protease inhibitor-containing antiretroviral therapy on endothelial function in HIV-infected persons: randomisedcontrolled trial,”Heart,v o l .9 5 ,n o .5 ,p p .
  23. (2009). Efficacy and safety of switching from boosted lopinavir to boosted atazanavir in patients with virological suppression receiving a lpv/r-containing haart: the atazip study,”
  24. (2008). Endothelial function in human immunodeficiency virus-infected antiretroviral-naive subjects before and after starting potent antiretroviral therapy.
  25. (1998). Enterovirus infections as a possible risk factor for myocardial infarction,”
  26. (2008). Epidemiological evidence for cardiovascular disease in HIV-infected patients and relationship to highly active antiretroviral therapy,”
  27. (2002). Evidence for infectious agents in cardiovascular disease and atherosclerosis,”
  28. (2001). Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III),”
  29. (2007). Ezetimibe is effective when added to maximally tolerated lipid lowering therapy
  30. (2006). Ezetimibe, a promising lipid-lowering agent for the treatment of dyslipidaemia in HIV-infected patients with poor response to statins,”
  31. (2007). Ezetimibe’s effects on the LDL cholesterol levels of HIV-infected patients receiving HAART,”
  32. (2005). Fichtenbaum et al., “Effect of efavirenz on the pharmacokinetics of simvastatin, atorvastatin, and pravastatin: results of AIDS clinical trials group 5108 study,”
  33. (2007). First Italian consensus statement on diagnosis, prevention and treatment of cardiovascular complications in HIV-infected patients
  34. (2009). Gemini: a noninferiority study of saquinavir/ritonavir versus lopinavir/ritonavir as initial HIV-I therapy in adults,”
  35. (2006). Group, “CD4+-guided interruption of antiretroviral treatment,” The New England
  36. (2000). h u ,A .A .Q u y y u m i ,J .E .N o r m a ne ta l . ,“ E ffects of total pathogen burden on coronary artery disease risk and
  37. (2004). Heart disease: the greatest ’risk’ factor of them all,”
  38. (2008). HIV replication enhances production of free fatty acids, low density lipoproteins and many key proteins involved in lipid metabolism: a proteomics study,”
  39. (2008). Human immunodeficiencyvirus(HIV)infectshumanarterialsmooth muscle cells in vivo and in vitro: implications for the pathogenesis of HIV-mediated vascular disease,”
  40. (2002). i l l e r ,D .B r o w n ,J .A m i ne ta l . ,“ Ar a n d o m i z e d ,d o u b l e -blind study of gemfibrozil for the treatment of protease inhibitor-associated hypertriglyceridaemia,”
  41. (2003). Impact of HIV infection and HAART on serum lipids in men,”
  42. (2006). Improved lipid profiles and maintenance of virologic control in heavily pretreated hiv-infected patients who switched from stavudine to tenofovir treatment,” Clinical Infectious Diseases,
  43. (2005). Improvement in dyslipidaemia after switching stavudine to tenofovir and replacing protease inhibitors with efavirenz in HIVinfected children,”
  44. (2008). Improvement in insulin sensitivity and dyslipidemia in protease inhibitor-treated adult male patients after switch to atazanavir/ritonavir,”
  45. (2009). Improvement in lipid profiles in antiretroviral-experienced HIV-positive patients with hyperlipidemia after a switch to unboosted atazanavir,”
  46. (2007). Incidence and causesofdeathinHIV-infectedpersonsreceivinghighlyactive antiretroviral therapy compared with estimates for the general population of similar age and from the same geographical area,”
  47. (1993). Increased de novo hepatic lipogenesis in human immunodeficiency virus infection,”
  48. (1999). Infection and atherosclerosis: emerging mechanistic paradigms,”
  49. (2005). Infection, antibiotics, and atherothrombosis—end of the road or new beginnings?” The New England
  50. (2002). Interactions between antiretroviral drugs and drugs used for the therapy of the metabolic complications encountered during
  51. (2008). J.G.Gerber,D.W.Kitch,C.J.Fichtenbaumetal.,“Fishoiland fenofibrate for the treatment of hypertriglyceridemia in HIVinfected subjects on antiretroviral therapy:
  52. (2008). Lipid-lowering efficacy and safety after switching to atazanavir-ritonavirbased highly active antiretroviral therapy in patients with human immunodeficiency virus,”
  53. Long-term cocaine use and antiretroviral therapy are associated with silent coronary artery disease
  54. (2002). Long-term metabolic consequences of switching from protease inhibitors to efavirenz in therapy for human immunodeficiency virusinfectedpatientswithlipoatrophy,”ClinicalInfectiousDiseases,
  55. (1998). M e i e r ,S .S .J i c k ,L .E .D e r b y ,C .V a s i l a k i s ,a n dH .J i c k , “Acute respiratory-tract infections and risk of first-time acute myocardial infarction,”
  56. (2008). Metabolic and immune activation effects of treatment interruption in chronic HIV-1 infection: implications for cardiovascular risk,”
  57. (2010). Once-daily atazanavir/ritonavir compared with twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-na¨ ıve HIV1-infected patients: 96-week efficacy and safety results of the CASTLE study,”
  58. (2009). Once-daily darunavir/ritonavir vs. lopinavir/ritonavir in treatment-naive, HIV-1-infected patients: 96-week analysis,”
  59. (2008). Outcome of protease inhibitor substitution with nevirapine
  60. (2007). Perier et al., “Reduction in triglyceride level with N-3 polyunsaturated fatty acids in HIV-infected patients taking potent antiretroviral therapy: a randomized prospective study,”
  61. (2007). Pharmacokinetic drug-drug interaction between the new HIV protease inhibitor darunavir (TMC114) and the lipid-lowering agent pravastatin,”
  62. (2007). Pharmacokinetics and pharmacodynamics of combined use of lopinavir/ritonavirandrosuvastatininHIV-infectedpatients,”
  63. (2007). R¨ o l i n g ,F .D .G o e b e l ,a n dJ .R . Bogner, “Metabolic and anthropometric changes one year after switching from Didanosine/Stavudine to Tenofovir in HIV-infected patients,”
  64. (2009). Response to newly prescribed lipid-lowering therapy in patients with and without
  65. (2010). 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,”
  66. (1998). Role of infection as a risk factor for atherosclerosis, myocardial infarction, and stroke,”
  67. (2004). Serum adiponectin and metabolic parameters in HIV-I-infected patients after substitution of nevirapine for protease inhibitors,”
  68. (1997). Serum lipid and lipoprotein patterns in patients with liver cirrhosis and chronic active hepatitis,”
  69. Substituting abacavir for hyperlipidemia-associated protease inhibitors in HAART regimens improves fasting lipid profiles, maintains virologic suppression, and simplifies treatment,”
  70. (2003). Substitution of nevirapine, efavirenz, or abacavir for protease inhibitors in patients with human immunodeficiency virus infection,” The New England
  71. (2006). Sustained improvement of dyslipidaemia in HAART-treated patients replacing stavudine with tenofovir,”
  72. (2006). Switch from efavirenz to nevirapine associated with resolution of efavirenz-related neuropsychiatric adverse events and improvement
  73. (2006). Switch to abacavir-based triple nucleoside regimens in HIV-1 infected patients never treated with suboptimal antiretroviral therapy: a review,”
  74. (2010). Switching the nucleoside reverse transcriptase inhibitor backbone to tenofovir disoproxil fumarate+emtricitabine promptly improves triglycerides and low-density lipoprotein cholesterol in dyslipidaemic patients,”
  75. (2007). Switching to a protease inhibitor-containing, nucleoside-sparing regimen12 Cholesterol (lopinavir/ritonavir plus efavirenz) increases limb fat but raises serum lipid levels: results of a prospective randomized trial (AIDS clinical trial group 5125s),”
  76. (2005). Switching to atazanavir improves metabolic disorders in antiretroviral-experienced patients with severe hyperlipidemia,”
  77. (2007). The impact of reducing stavudine dose versus switching to tenofovir on plasma lipids, body composition and mitochondrial function in HIV-infected patients,” Antiviral Therapy,v o l .1 2 ,n o .3 ,p p .
  78. (2006). The KLEAN study of fosamprenavir-ritonavir versus lopinavir-ritonavir, each in combination with abacavir-lamivudine, for initial treatment of HIV infection over 48 weeks: a randomised non-inferiority trial,”
  79. (2007). The safety and efficacy of switching stavudine to tenofovir DF in combinationwithlamivudineandefavirenzinHIV-1-infected patients: three-year follow-up after switching therapy,”
  80. (1992). Tumor necrosis factor, interleukin, and interferon induced changes in lipid metabolism as part of host defense,”
  81. (2008). V.Soriano,P.Garc´ ıa-Gasco,E.Vispoetal.,“Efficacyandsafety ofreplacinglopinavirwithatazanavirinHIV-infectedpatients with undetectable plasma viraemia: final results of the SLOAT trial,”JournalofAntimicrobialChemotherapy,vol.61,no .1,pp .
  82. (2002). Virological, immunological, and clinical impact of switching from protease inhibitors to nevirapine or to efavirenz in patients with human immunodeficiency virus infection and long-lasting viral suppression,” Clinical Infectious Diseases,