Dyslipidemias pp 155-176 | Cite as

Dyslipidemia in HIV-Infected Patients

  • Frederick J. LeeEmail author
  • Andrew Carr
Part of the Contemporary Endocrinology book series (COE)


Derangements of lipid metabolism are a common finding in human immunodeficiency virus (HIV) infection, and may lead to increased cardiovascular risk. Untreated HIV infection results in an initial fall of high-density lipoprotein (HDL) cholesterol, followed by declines in non-HDL cholesterol fractions. With progression to the acquired immune deficiency syndrome (AIDS), serum triglyceride levels rise. These changes appear principally driven by inflammation accompanying ongoing viral replication, and correlate with levels of the pro-inflammatory cytokines interferon-α and tumour necrosis factor-α. HIV protein products (nef, tat, gp120) may also exert direct effects on lipid metabolism. dyslipidemias persist despite treatment with antiretroviral therapy (ART). Lipodystrophy associated with thymidine analogue therapy is strongly associated with elevated triglycerides, total and non-HDL cholesterol, and depressed HDL cholesterol. Most ART drugs lead to mixed lipid derangements, but there is considerable variability both between and within the different ART classes in their effects, and do not necessarily equate to increased cardiovascular risk. Protease inhibitors (PI) are the class most associated with dyslipidemia and cardiovascular risk. Newer ART classes (integrase inhibitors, chemokine receptor 5 entry antagonists) have minimal lipid effects, although long-term cardiovascular event data are lacking. Treatment options for dyslipidemia include switching from PI therapy or initiating statin therapy; both are feasible, although it is unknown which is superior. There are no data for the endpoint of risk reduction with treatment, and this is an area requiring further study.


Antiretroviral therapy Protease inhibitors HIV Cardiovascular risk dyslipidemia 


  1. 1.
    Weber R, Ruppik M, Rickenbach M, et al. Decreasing mortality and changing patterns of causes of death in the Swiss HIV cohort study. HIV Med. 2012.Google Scholar
  2. 2.
    Palella FJ Jr., Baker RK, Moorman AC, et al. 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(1):27–34.PubMedGoogle Scholar
  3. 3.
    Antiretroviral Therapy Cohort Collaboration. Causes of death in HIV-1-infected patients treated with antiretroviral therapy, 1996–2006: collaborative analysis of 13 HIV cohort studies. Clin Infect Dis. 2010;50(10):1387–96.Google Scholar
  4. 4.
    Saves M, Chene G, Ducimetiere P, et al. Risk factors for coronary heart disease in patients treated for human immunodeficiency virus infection compared with the general population. Clin Infect Dis. 2003;37(2):292–8.PubMedGoogle Scholar
  5. 5.
    Chow FC, Regan S, Feske S, Meigs JB, Grinspoon SK, Triant VA. Comparison of ischemic stroke incidence in HIV-infected and non-HIV-infected patients in a US health care system. J Acquir Immune Defic Syndr. 2012;60(4):351–8.PubMedCentralPubMedGoogle Scholar
  6. 6.
    Aberg JA. Cardiovascular complications in HIV management: past, present, and future. J Acquir Immune Defic Syndr. 2009;50(1):54–64.PubMedCentralPubMedGoogle Scholar
  7. 7.
    Grunfeld C, Kotler DP, Hamadeh R, Tierney A, Wang J, Pierson RN. Hypertriglyceridemia in the acquired immunodeficiency syndrome. Am J Med. 1989;86(1):27–31.PubMedGoogle Scholar
  8. 8.
    Grunfeld C, Pang M, Doerrler W, Shigenaga JK, Jensen P, Feingold KR. Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. J Clin Endocrinol Metab. 1992;74(5):1045–52.PubMedGoogle Scholar
  9. 9.
    Riddler SA, Smit E, Cole SR, et al. Impact of HIV infection and HAART on serum lipids in men. JAMA. 2003;289(22):2978–82.PubMedGoogle Scholar
  10. 10.
    Barter P, Gotto AM, LaRosa JC, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007;357(13):1301–10.PubMedGoogle Scholar
  11. 11.
    Barter P. Effects of inflammation on high-density lipoproteins. Arterioscler Thromb Vasc Biol. 2002;22(7):1062–3.PubMedGoogle Scholar
  12. 12.
    Asztalos BF, Schaefer EJ, Horvath KV, et al. Protease inhibitor-based HAART, HDL, and CHD-risk in HIV-infected patients. Atherosclerosis. 2006;184(1):72–7.PubMedGoogle Scholar
  13. 13.
    El-Sadr WM, Lundgren JD, Neaton JD, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355(22):2283–96.PubMedGoogle Scholar
  14. 14.
    Mildvan D, Machado SG, Wilets I, Grossberg SE. Endogenous interferon and triglyceride concentrations to assess response to zidovudine in AIDS and advanced AIDS-related complex. Lancet. 1992;339(8791):453–6.PubMedGoogle Scholar
  15. 15.
    Armstrong C, Liu E, Okuma J, et al. Dyslipidemia in an HIV-positive antiretroviral treatment-naive population in Dar es Salaam, Tanzania. J Acquir Immune Defic Syndr. 2011;57(2):141–5.PubMedCentralPubMedGoogle Scholar
  16. 16.
    Adewole OO, Eze S, Betiku Y, et al. Lipid profile in HIV/AIDS patients in Nigeria. Afr Health Sci. 2010;10(2):144–9.PubMedCentralPubMedGoogle Scholar
  17. 17.
    Hsue PY, Ordovas K, Lee T, et al. Carotid intima-media thickness among human immunodeficiency virus-infected patients without coronary calcium. Am J Cardiol. 2012;109(5):742–7.PubMedCentralPubMedGoogle Scholar
  18. 18.
    Mujawar Z, Rose H, Morrow MP, et al. Human immunodeficiency virus impairs reverse cholesterol transport from macrophages. PLoS Biol. 2006;4(11):e365.PubMedCentralPubMedGoogle Scholar
  19. 19.
    Rose H, Hoy J, Woolley I, et al. HIV infection and high density lipoprotein metabolism. Atherosclerosis. 2008;199(1):79–86.PubMedCentralPubMedGoogle Scholar
  20. 20.
    Matzen K, Dirkx AE, oude Egbrink MG, et al. HIV-1 Tat increases the adhesion of monocytes and T-cells to the endothelium in vitro and in vivo: implications for AIDS-associated vasculopathy. Virus Res. 2004;104(2):145–55.PubMedGoogle Scholar
  21. 21.
    Ren Z, Yao Q, Chen C. HIV-1 envelope glycoprotein 120 increases intercellular adhesion molecule-1 expression by human endothelial cells. Lab Invest. 2002;82(3):245–55.PubMedGoogle Scholar
  22. 22.
    Chung CP, Oeser A, Solus J, et al. Inflammatory mechanisms affecting the lipid profile in patients with systemic lupus erythematosus. J Rheumatol. 2007;34(9):1849–54.PubMedGoogle Scholar
  23. 23.
    Georgiadis AN, Papavasiliou EC, Lourida ES, et al. Atherogenic lipid profile is a feature characteristic of patients with early rheumatoid arthritis: effect of early treatment—a prospective, controlled study. Arthritis Res Ther. 2006;8(3):R82.PubMedCentralPubMedGoogle Scholar
  24. 24.
    Feingold KR, Grunfeld C. The acute phase response inhibits reverse cholesterol transport. J Lipid Res. 2010;51(4):682–4.PubMedCentralPubMedGoogle Scholar
  25. 25.
    Khovidhunkit W, Kim MS, Memon RA, et al. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host. J Lipid Res. 2004;45(7):1169–96.PubMedGoogle Scholar
  26. 26.
    Grunfeld C, Kotler DP, Shigenaga JK, et al. Circulating interferon-alpha levels and hypertriglyceridemia in the acquired immunodeficiency syndrome. Am J Med. 1991;90(2):154–62.PubMedGoogle Scholar
  27. 27.
    Shinohara E, Yamashita S, Kihara S, et al. Interferon alpha induces disorder of lipid metabolism by lowering postheparin lipases and cholesteryl ester transfer protein activities in patients with chronic hepatitis C. Hepatology. 1997;25(6):1502–6.PubMedGoogle Scholar
  28. 28.
    Haugaard SB, Andersen O, Pedersen SB, et al. Tumor necrosis factor alpha is associated with insulin-mediated suppression of free fatty acids and net lipid oxidation in HIV-infected patients with lipodystrophy. Metabolism. 2006;55(2):175–82.PubMedGoogle Scholar
  29. 29.
    Department of Health and Human Services (DHHS) Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Rockville, Maryland, USA: Department of Health and Human Services; 2013 [updated February 12].Google Scholar
  30. 30.
    Fischl MA, Richman DD, Grieco MH, et al. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987;317(4):185–91.PubMedGoogle Scholar
  31. 31.
    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(7):F51–8.PubMedGoogle Scholar
  32. 32.
    Martinez E, Mocroft A, Garcia-Viejo MA, et al. Risk of lipodystrophy in HIV-1-infected patients treated with protease inhibitors: a prospective cohort study. Lancet. 2001;357(9256):592–8.PubMedGoogle Scholar
  33. 33.
    Bogner JR, Vielhauer V, Beckmann RA, et al. Stavudine versus zidovudine and the development of lipodystrophy. J Acquir Immune Defic Syndr. 2001;27(3):237–44.PubMedGoogle Scholar
  34. 34.
    Carr A, Samaras K, Chisholm DJ, Cooper DA. Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet. 1998;351(9119):1881–3.PubMedGoogle Scholar
  35. 35.
    Carr A, Miller J, Law M, Cooper DA. A syndrome of lipoatrophy, lactic acidaemia and liver dysfunction associated with HIV nucleoside analogue therapy: contribution to protease inhibitor-related lipodystrophy syndrome. AIDS. 2000;14(3):F25–32.PubMedGoogle Scholar
  36. 36.
    Martinez E, Conget I, Lozano L, Casamitjana R, Gatell JM. Reversion of metabolic abnormalities after switching from HIV-1 protease inhibitors to nevirapine. AIDS. 1999;13(7):805–10.PubMedGoogle Scholar
  37. 37.
    Caron M, Auclair M, Vigouroux C, Glorian M, Forest C, Capeau J. The HIV protease inhibitor indinavir impairs sterol regulatory element-binding protein-1 intranuclear localization, inhibits preadipocyte differentiation, and induces insulin resistance. Diabetes. 2001;50(6):1378–88.PubMedGoogle Scholar
  38. 38.
    Coffinier C, Hudon SE, Farber EA, et al. HIV protease inhibitors block the zinc metalloproteinase ZMPSTE24 and lead to an accumulation of prelamin A in cells. Proc Natl Acad Sci U S A. 2007;104(33):13432–7.PubMedCentralPubMedGoogle Scholar
  39. 39.
    Mallal SA, John M, Moore CB, James IR, McKinnon EJ. Contribution of nucleoside analogue reverse transcriptase inhibitors to subcutaneous fat wasting in patients with HIV infection. AIDS. 2000;14(10):1309–16.PubMedGoogle Scholar
  40. 40.
    de Waal R, Cohen K, Maartens G. Systematic review of antiretroviral-associated lipodystrophy: lipoatrophy, but not central fat gain, is an antiretroviral adverse drug reaction. PLoS One. 2013;8(5):e63623.PubMedCentralPubMedGoogle Scholar
  41. 41.
    van der Valk M, Gisolf EH, Reiss P, et al. Increased risk of lipodystrophy when nucleoside analogue reverse transcriptase inhibitors are included with protease inhibitors in the treatment of HIV-1 infection. AIDS. 2001;15(7):847–55.PubMedGoogle Scholar
  42. 42.
    Thiebaut R, Daucourt V, Mercie P, et al. Lipodystrophy, metabolic disorders, and human immunodeficiency virus infection: Aquitaine Cohort, France, 1999. Groupe d'Epidemiologie Clinique du Syndrome d'Immunodeficience Acquise en Aquitaine. Clin Infect Dis. 2000;31(6):1482–7.PubMedGoogle Scholar
  43. 43.
    Hadigan C, Meigs JB, Corcoran C, et al. Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy. Clin Infect Dis. 2001;32(1):130–9.PubMedGoogle Scholar
  44. 44.
    Heath KV, Hogg RS, Chan KJ, et al. Lipodystrophy-associated morphological, cholesterol and triglyceride abnormalities in a population-based HIV/AIDS treatment database. AIDS. 2001;15(2):231–9.PubMedGoogle Scholar
  45. 45.
    Galli M, Veglia F, Angarano G, et al. Gender differences in antiretroviral drug-related adipose tissue alterations. Women are at higher risk than men and develop particular lipodystrophy patterns. J Acquir Immune Defic Syndr. 2003;34(1):58–61.PubMedGoogle Scholar
  46. 46.
    Carr A, Workman C, Smith DE, et al. Abacavir substitution for nucleoside analogs in patients with HIV lipoatrophy: a randomized trial. JAMA. 2002;288(2):207–15.PubMedGoogle Scholar
  47. 47.
    Tebas P, Zhang J, Yarasheski K, et al. Switching to a protease inhibitor-containing, nucleoside-sparing regimen (lopinavir/ritonavir plus efavirenz) increases limb fat but raises serum lipid levels: results of a prospective randomized trial (AIDS clinical trial group 5125s). J Acquir Immune Defic Syndr. 2007;45(2):193–200.PubMedGoogle Scholar
  48. 48.
    Carey DL, Baker D, Rogers GD, et al. A randomized, multicenter, open-label study of poly-L-lactic acid for HIV-1 facial lipoatrophy.J Acquir Immune Defic Syndr. 2007;46(5):581–9.PubMedGoogle Scholar
  49. 49.
    Silvers SL, Eviatar JA, Echavez MI, Pappas AL. Prospective, open-label, 18-month trial of calcium hydroxylapatite (Radiesse) for facial soft-tissue augmentation in patients with human immunodeficiency virus-associated lipoatrophy: one-year durability. Plast Reconstr Surg. 2006;118(3 Suppl):34S–45S.PubMedGoogle Scholar
  50. 50.
    Slama L, Lanoy E, Valantin MA, et al. Effect of pioglitazone on HIV-1-related lipodystrophy: a randomized double-blind placebo-controlled trial (ANRS 113). Antivir Ther. 2008;13(1):67–76.PubMedGoogle Scholar
  51. 51.
    Falutz J, Allas S, Blot K, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med. 2007;357(23):2359–70.PubMedGoogle Scholar
  52. 52.
    Falutz J, Potvin D, Mamputu JC, et al. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension. J Acquir Immune Defic Syndr. 2010;53(3):311–22.PubMedGoogle Scholar
  53. 53.
    Falutz J, Allas S, Mamputu JC, et al. Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation. AIDS. 2008;22(14):1719–28.PubMedGoogle Scholar
  54. 54.
    Hadigan C, Corcoran C, Basgoz N, Davis B, Sax P, Grinspoon S. Metformin in the treatment of HIV lipodystrophy syndrome: a randomized controlled trial. JAMA. 2000;284(4):472–7.PubMedGoogle Scholar
  55. 55.
    Mulligan K, Grunfeld C, Tai VW, et al. Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection. J Acquir Immune Defic Syndr. 2000;23(1):35–43.Google Scholar
  56. 56.
    Periard D, Telenti A, Sudre P, et al. Atherogenic dyslipidemia in HIV-infected individuals treated with protease inhibitors. The Swiss HIV Cohort Study. Circulation. 1999;100(7):700–5.PubMedGoogle Scholar
  57. 57.
    Riddler SA, Li X, Otvos J, et al. Antiretroviral therapy is associated with an atherogenic lipoprotein phenotype among HIV-1-infected men in the Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr. 2008;48(3):281–8.PubMedGoogle Scholar
  58. 58.
    Carr A, Samaras K, Thorisdottir A, Kaufmann GR, Chisholm DJ, Cooper DA. Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet. 1999;353(9170):2093–99.PubMedGoogle Scholar
  59. 59.
    Dragsted UB, Gerstoft J, Pedersen C, et al. Randomized trial to evaluate indinavir/ritonavir versus saquinavir/ritonavir in human immunodeficiency virus type 1-infected patients: the MaxCmin1 Trial. J Infect Dis. 2003;188(5):635–42.PubMedGoogle Scholar
  60. 60.
    Fontas E, van Leth F, Sabin CA, et al. Lipid profiles in HIV-infected patients receiving combination antiretroviral therapy: are different antiretroviral drugs associated with different lipid profiles? J Infect Dis. 2004;189(6):1056–74.PubMedGoogle Scholar
  61. 61.
    Mallolas J, Podzamczer D, Milinkovic A, et al. 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. J Acquir Immune Defic Syndr. 2009;51(1):29–36.PubMedGoogle Scholar
  62. 62.
    Martinez 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(11):1697–707.PubMedGoogle Scholar
  63. 63.
    Mills AM, Nelson M, Jayaweera D, et al. Once-daily darunavir/ritonavir vs. lopinavir/ritonavir in treatment-naive, HIV-1-infected patients: 96-week analysis. AIDS. 2009;23(13):1679–88.PubMedGoogle Scholar
  64. 64.
    Molina JM, Andrade-Villanueva J, Echevarria J, et al. Once-daily atazanavir/ritonavir compared with twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 96-week efficacy and safety results of the CASTLE study. J Acquir Immune Defic Syndr. 2010;53(3):323–32.PubMedGoogle Scholar
  65. 65.
    Aberg JA, Tebas P, Overton ET, et al. Metabolic effects of darunavir/ritonavir versus atazanavir/ritonavir in treatment-naive, HIV type 1-infected subjects over 48 weeks. AIDS Res Hum Retroviruses. 2012;28(10):1184–95.PubMedCentralPubMedGoogle Scholar
  66. 66.
    Minami R, Yamamoto M, Takahama S, Ando H, Miyamura T, Suematsu E. Comparison of the influence of four classes of HIV antiretrovirals on adipogenic differentiation: the minimal effect of raltegravir and atazanavir. J Infect Chemother. 2011;17(2):183–8.PubMedGoogle Scholar
  67. 67.
    Friis-Moller N, Reiss P, Sabin CA, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med. 2007;356(17):1723–35.PubMedGoogle Scholar
  68. 68.
    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(3):318–30.PubMedGoogle Scholar
  69. 69.
    Monforte A, Reiss P, Ryom L, et al. Atazanavir is not associated with an increased risk of cardio or cerebrovascular disease events. AIDS. 2013;27(3):407–15.PubMedGoogle Scholar
  70. 70.
    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;1(1):e19.PubMedCentralPubMedGoogle Scholar
  71. 71.
    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(2):191–201.PubMedGoogle Scholar
  72. 72.
    Gallant JE, DeJesus E, Arribas JR, et al. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med. 2006;354(3):251–60.PubMedGoogle Scholar
  73. 73.
    Crane HM, Grunfeld C, Willig JH, et al. Impact of NRTIs on lipid levels among a large HIV-infected cohort initiating antiretroviral therapy in clinical care. AIDS. 2011;25(2):185–95.PubMedGoogle Scholar
  74. 74.
    Sax PE, Tierney C, Collier AC, et al. Abacavir-lamivudine versus tenofovir-emtricitabine for initial HIV-1 therapy. N Engl J Med. 2009;361(23):2230–40.PubMedCentralPubMedGoogle Scholar
  75. 75.
    Smith KY, Patel P, Fine D, et al. Randomized, double-blind, placebo-matched, multicenter trial of abacavir/lamivudine or tenofovir/emtricitabine with lopinavir/ritonavir for initial HIV treatment. AIDS. 2009;23(12):1547–56.PubMedGoogle Scholar
  76. 76.
    Post FA, Moyle GJ, Stellbrink HJ, et al. Randomized comparison of renal effects, efficacy, and safety with once-daily abacavir/lamivudine versus tenofovir/emtricitabine, administered with efavirenz, in antiretroviral-naive, HIV-1-infected adults: 48-week results from the ASSERT study. J Acquir Immune Defic Syndr. 2010;55(1):49–57.PubMedGoogle Scholar
  77. 77.
    Moyle GJ, Sabin CA, Cartledge J, et al. A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy. AIDS. 2006;20(16):2043–50.PubMedGoogle Scholar
  78. 78.
    Behrens G, Maserati R, Rieger A, et al. Switching to tenofovir/emtricitabine from abacavir/lamivudine in HIV-infected adults with raised cholesterol: effect on lipid profiles. Antivir Ther. 2012;17(6):1011–20.PubMedGoogle Scholar
  79. 79.
    Sabin CA, Worm SW, Weber R, et al. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration. Lancet. 2008;371(9622):1417–26.PubMedGoogle Scholar
  80. 80.
    Strategies for Management of Anti-Retroviral Therapy/INSIGHT, DAD Study Groups. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients. AIDS. 2008;22(14):F17–24.Google Scholar
  81. 81.
    Ribaudo HJ, Benson CA, Zheng Y, et al. No risk of myocardial infarction associated with initial antiretroviral treatment containing abacavir: short and long-term results from ACTG A5001/ALLRT. Clin Infect Dis. 2011;52(7):929–40.PubMedCentralPubMedGoogle Scholar
  82. 82.
    Ding X, Andraca-Carrera E, Cooper C, et al. No association of abacavir use with myocardial infarction: findings of an FDA Meta-analysis. J Acquir Immune Defic Syndr. 2012;61(4):441–7.PubMedGoogle Scholar
  83. 83.
    Lennox JL, Dejesus E, Berger DS, et al. Raltegravir versus Efavirenz regimens in treatment-naive HIV-1-infected patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses. J Acquir Immune Defic Syndr. 2010;55(1):39–48.PubMedGoogle Scholar
  84. 84.
    Curran A, Gutirerrez M, Deig E, et al. Efficacy, safety and pharmacokinetics of 900/100 mg of darunavir/ritonavir once daily in treatment-experienced patients. J Antimicrob Chemother. 2010;65(10):2195–203.PubMedGoogle Scholar
  85. 85.
    van Lunzen J, Maggiolo F, Arribas JR, et al. Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naive adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging, randomized, phase 2b trial. Lancet Infect Dis. 2012;12(2):111–8.PubMedGoogle Scholar
  86. 86.
    Sierra-Madero J, Di Perri G, Wood R, et al. Efficacy and safety of maraviroc versus efavirenz, both with zidovudine/lamivudine: 96-week results from the MERIT study. HIV Clin Trials. 2010;11(3):125–32.PubMedGoogle Scholar
  87. 87.
    Cooper DA, Cordery DV, Reiss P, et al. The effects of enfuvirtide therapy on body composition and metabolic parameters over 48 weeks in the TORO body imaging substudy. HIV Med. 2011;12(1):31–9.PubMedGoogle Scholar
  88. 88.
    Elion R, Cohen C, Gathe J, et al. Phase 2 study of cobicistat versus ritonavir each with once-daily atazanavir andfixed-dose emtricitabine/tenofovir df in the initial treatment of HIV infection. AIDS. 2011;25(15):1881–6.PubMedGoogle Scholar
  89. 89.
    Lee GA, Seneviratne T, Noor MA, et al. The metabolic effects of lopinavir/ritonavir in HIV-negative men. AIDS. 2004;18(4):641–9.PubMedCentralPubMedGoogle Scholar
  90. 90.
    Samaras K, Richardson R, Carr A. Postprandial lipid effects of low-dose ritonavir vs. raltegravir in HIV-uninfected adults. AIDS. 2010;24(11):1727–31.PubMedGoogle Scholar
  91. 91.
    Foulkes AS, Wohl DA, Frank I, et al. Associations among race/ethnicity, ApoC-III genotypes, and lipids in HIV-1-infected individuals on antiretroviral therapy. PLoS Med. 2006;3(3):e52.PubMedCentralPubMedGoogle Scholar
  92. 92.
    Guardiola M, Ferre R, Salazar J, et al. Protease inhibitor-associated dyslipidemia in HIV-infected patients is strongly influenced by the APOA5–1131T- > C gene variation. Clin Chem. 2006;52(10):1914–9.PubMedGoogle Scholar
  93. 93.
    Mahungu TW, Nair D, Smith CJ, et al. The relationships of ABCB1 3435C > T and CYP2B6 516G > T with high-density lipoprotein cholesterol in HIV-infected patients receiving Efavirenz. Clin Pharmacol Ther. 2009;86(2):204–11.PubMedGoogle Scholar
  94. 94.
    Wyen C, Hendra H, Vogel M, et al. Impact of CYP2B6 983T > C polymorphism on non-nucleoside reverse transcriptase inhibitor plasma concentrations in HIV-infected patients. J Antimicrob Chemother. 2008;61(4):914–8.PubMedCentralPubMedGoogle Scholar
  95. 95.
    Clotet B, Bellos N, Molina JM, et al. Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomized trials. Lancet. 2007;369(9568):1169–78.PubMedGoogle Scholar
  96. 96.
    Lundgren JD, Battegay M, Behrens G, et al. European AIDS Clinical Society (EACS) guidelines on the prevention and management of metabolic diseases in HIV. HIV Med. 2008;9(2):72–81.PubMedGoogle Scholar
  97. 97.
    Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. 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). JAMA. 2001;285(19):2486–97.Google Scholar
  98. 98.
    Dube MP, Stein JH, Aberg JA, et al. Guidelines for the evaluation and management of dyslipidemia in human immunodeficiency virus (HIV)-infected adults receiving antiretroviral therapy: recommendations of the HIV Medical Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group. Clin Infect Dis. 2003;37(5):613–27.PubMedGoogle Scholar
  99. 99.
    Law MG, Friis-Moller N, El-Sadr WM, et al. The use of the Framingham equation to predict myocardial infarctions in HIV-infected patients: comparison with observed events in the D:A:DStudy. HIV Med. 2006;7(4):218–30.PubMedGoogle Scholar
  100. 100.
    Friis-Moller N, Thiebaut R, Reiss P, et al. Predicting the risk of cardiovascular disease in HIV-infected patients: the data collection on adverse effects of anti-HIV drugs study. Eur J Cardiovasc Prev Rehabil. 2010;17(5):491–501.PubMedGoogle Scholar
  101. 101.
    Sabin CA, d’Arminio Monforte A, Friis-Moller N, et al. Changes over time in risk factors for cardiovascular disease and use of lipid-lowering drugs in HIV-infected individuals and impact on myocardial infarction. Clin Infect Dis. 2008;46(7):1101–10.PubMedGoogle Scholar
  102. 102.
    Freiberg MS, Leaf DA, Goulet JL, et al. The association between the receipt of lipid lowering therapy and HIV status among veterans who met NCEP/ATP III criteria for the receipt of lipid lowering medication. J Gen Intern Med. 2009;24(3):334–40.PubMedCentralPubMedGoogle Scholar
  103. 103.
    Calza L, Manfredi R, Colangeli V, et al. Substitution of nevirapine or efavirenz for protease inhibitor versus lipid-lowering therapy for the management of dyslipidemia. AIDS. 2005;19(10):1051–8.PubMedGoogle Scholar
  104. 104.
    Eron JJ, Young B, Cooper DA, et al. Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viremia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomized controlled trials. Lancet. 2010;375(9712):396–407.PubMedGoogle Scholar
  105. 105.
    Gil P, de Gorgolas M, Estrada V, et al. Long-term efficacy and safety of protease inhibitor switching to nevirapine in HIV-infected patients with undetectable virus load. Clin Infect Dis. 2004;39(7):1024–9.PubMedGoogle Scholar
  106. 106.
    Palella F, Tebas P, Gazzard B, et al. SPIRIT study: switching to emtricitabine/rilpivirine/tenofovir DF (FTC/RPV/TDF) single-tablet regimen (STR) from a ritonavir-boosted protease inhibitor and two nucleoside reverse transcriptase inhibitors (NRTIs) maintains HIV suppression and improves serum lipids (Abstract TUAB0104). 19th International AIDS Conference. Washington, DC, USA July 22–27, 2012.Google Scholar
  107. 107.
    Parienti JJ, Massari V, Rey D, Poubeau P, Verdon R. Efavirenz to nevirapine switch in HIV-1-infected patients with dyslipidemia: a randomized, controlled study. Clin Infect Dis. 2007;45(2):263–6.PubMedGoogle Scholar
  108. 108.
    Silverberg MJ, Leyden W, Hurley L, et al. Response to newly prescribed lipid-lowering therapy in patients with and without HIV infection. Ann Intern Med. 2009;150(5):301–13.PubMedGoogle Scholar
  109. 109.
    Fichtenbaum CJ, Gerber JG. Interactions between antiretroviral drugs and drugs used for the therapy of the metabolic complications encountered during HIV infection. Clin Pharmacokinet. 2002;41(14):1195–211.PubMedGoogle Scholar
  110. 110.
    Fichtenbaum CJ, Gerber JG, Rosenkranz SL, et al. Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047. AIDS. 2002;16(4):569–77.PubMedGoogle Scholar
  111. 111.
    Aslangul E, Assoumou L, Bittar R, et al. Rosuvastatin versus pravastatin in dyslipidemic HIV-1-infected patients receiving protease inhibitors: a randomized trial. AIDS. 2010;24(1):77–83.PubMedGoogle Scholar
  112. 112.
    Singh S, Willig JH, Mugavero MJ, et al. Comparative effectiveness and toxicity of statins among HIV-infected patients. Clin Infect Dis. 2011;52(3):387–95.PubMedCentralPubMedGoogle Scholar
  113. 113.
    Aberg JA, Zackin RA, Brobst SW, et al. A randomized trial of the efficacy and safety of fenofibrate versus pravastatin in HIV-infected subjects with lipid abnormalities: AIDS Clinical Trials Group Study 5087. AIDS Res Hum Retroviruses. 2005;21(9):757–67.PubMedGoogle Scholar
  114. 114.
    Wohl DA, Tien HC, Busby M, et al. Randomized study of the safety and efficacy of fish oil (omega-3 fatty acid) supplementation with dietary and exercise counseling for the treatment of antiretroviral therapy-associated hypertriglyceridemia. Clin Infect Dis. 2005;41(10):1498–504.PubMedGoogle Scholar
  115. 115.
    Toth PP, Davidson MH. Cholesterol absorption blockade with ezetimibe. Curr Drug Targets Cardiovasc Haematol Disord. 2005;5(6):455–62.PubMedGoogle Scholar
  116. 116.
    Wohl DA, Waters D, Simpson RJ Jr, et al. Ezetimibe alone reduces low-density lipoprotein cholesterol in HIV-infected patients receiving combination antiretroviral therapy. Clin Infect Dis. 2008;47(8):1105–8.PubMedGoogle Scholar
  117. 117.
    Gerber MT, Mondy KE, Yarasheski KE, et al. Niacin in HIV-infected individuals with hyperlipidemia receiving potent antiretroviral therapy. Clin Infect Dis. 2004;39(3):419–25.PubMedGoogle Scholar
  118. 118.
    Penzak SR, Chuck SK. Hyperlipidemia associated with HIV protease inhibitor use: pathophysiology, prevalence, risk factors and treatment. Scand J Infect Dis. 2000;32(2):111–23.PubMedGoogle Scholar
  119. 119.
    Liang JS, Distler O, Cooper DA, et al. HIV protease inhibitors protect apolipoprotein B from degradation by the proteasome: a potential mechanism for protease inhibitor-induced hyperlipidemia. Nat Med. 2001;7(12):1327–31.PubMedGoogle Scholar
  120. 120.
    Riddle TM, Kuhel DG, Woollett LA, Fichtenbaum CJ, Hui DY. HIV protease inhibitor induces fatty acid and sterol biosynthesis in liver and adipose tissues due to the accumulation of activated sterol regulatory element-binding proteins in the nucleus. J Biol Chem. 2001;276(40):37514–9.PubMedGoogle Scholar
  121. 121.
    Gan SK, Samaras K, Thompson CH, et al. Altered myocellular and abdominal fat partitioning predict disturbance in insulin action in HIV protease inhibitor-related lipodystrophy. Diabetes. 2002;51(11):3163–9.PubMedGoogle Scholar
  122. 122.
    Zimmermann R, Panzenbock U, Wintersperger A, et al. Lipoprotein lipase mediates the uptake of glycated LDL in fibroblasts, endothelial cells, and macrophages. Diabetes. 2001;50(7):1643–53.PubMedGoogle Scholar
  123. 123.
    Miserez AR, Muller PY, Spaniol V. Indinavir inhibits sterol-regulatory element-binding protein-1c-dependent lipoprotein lipase and fatty acid synthase gene activations. AIDS. 2002;16(12):1587–94.PubMedGoogle Scholar
  124. 124.
    Petit JM, Duong M, Duvillard L, et al. LDL-receptors expression in HIV-infected patients: relations to antiretroviral therapy, hormonal status, and presence of lipodystrophy. Eur J Clin Invest. 2002;32(5):354–9.PubMedGoogle Scholar
  125. 125.
    Lenhard JM, Croom DK, Weiel JE, Winegar DA. HIV protease inhibitors stimulate hepatic triglyceride synthesis. Arterioscler Thromb Vasc Biol. 2000;20(12):2625–9.PubMedGoogle Scholar
  126. 126.
    Dressman J, Kincer J, Matveev SV, et al. HIV protease inhibitors promote atherosclerotic lesion formation independent of dyslipidemia by increasing CD36-dependent cholesteryl ester accumulation in macrophages. J Clin Invest. 2003;111(3):389–97.PubMedCentralPubMedGoogle Scholar
  127. 127.
    Fleischman A, Johnsen S, Systrom DM, et al. Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults. Am J Physiol Endocrinol Metab. 2007;292(6):E1666–73.PubMedCentralPubMedGoogle Scholar

Copyright information

© Humana Press 2015

Authors and Affiliations

  1. 1.Clinical Research Program, St. Vincent’s Centre for Applied Medical ResearchSt. Vincent’s HospitalSydneyAustralia

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