Skip to main content

Dyslipidemia in HIV-Infected Patients

  • Chapter
  • First Online:
Dyslipidemias

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  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. 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.

    CAS  PubMed  Google Scholar 

  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. 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.

    PubMed  Google Scholar 

  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.

    PubMed Central  PubMed  Google Scholar 

  6. Aberg JA. Cardiovascular complications in HIV management: past, present, and future. J Acquir Immune Defic Syndr. 2009;50(1):54–64.

    PubMed Central  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  11. Barter P. Effects of inflammation on high-density lipoproteins. Arterioscler Thromb Vasc Biol. 2002;22(7):1062–3.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed Central  CAS  PubMed  Google Scholar 

  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.

    PubMed Central  CAS  PubMed  Google Scholar 

  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.

    PubMed Central  CAS  PubMed  Google Scholar 

  18. Mujawar Z, Rose H, Morrow MP, et al. Human immunodeficiency virus impairs reverse cholesterol transport from macrophages. PLoS Biol. 2006;4(11):e365.

    PubMed Central  PubMed  Google Scholar 

  19. Rose H, Hoy J, Woolley I, et al. HIV infection and high density lipoprotein metabolism. Atherosclerosis. 2008;199(1):79–86.

    PubMed Central  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed Central  PubMed  Google Scholar 

  24. Feingold KR, Grunfeld C. The acute phase response inhibits reverse cholesterol transport. J Lipid Res. 2010;51(4):682–4.

    PubMed Central  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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. 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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed Central  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed Central  CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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. 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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed Central  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed Central  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed Central  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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. 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.

    PubMed Central  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed Central  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed Central  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed Central  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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. 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.

    PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed Central  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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. 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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed Central  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  115. Toth PP, Davidson MH. Cholesterol absorption blockade with ezetimibe. Curr Drug Targets Cardiovasc Haematol Disord. 2005;5(6):455–62.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed Central  CAS  PubMed  Google Scholar 

  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.

    PubMed Central  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Frederick J. Lee BSc, MBBS (Hons), FRACP, FRCPA .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Humana Press

About this chapter

Cite this chapter

Lee, F., Carr, A. (2015). Dyslipidemia in HIV-Infected Patients. In: Garg, A. (eds) Dyslipidemias. Contemporary Endocrinology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-424-1_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-424-1_9

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-423-4

  • Online ISBN: 978-1-60761-424-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics