Reviews

Coronary heart disease in people infected with HIV

Cleveland Clinic Journal of Medicine. 2010 August;77(8):547-556 | 10.3949/ccjm.77a.09119

ABSTRACTPeople infected with human immunodeficiency virus (HIV) are living longer thanks to effective antiretroviral therapy. As this population ages, cardiovascular disease is becoming an important cause of morbidity and death. The authors of this review discuss the magnitude and likely mechanisms of the risk and strategies for managing it.

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KEY POINTS

Traditional risk factors are the main contributors to cardiovascular disease in this population, although HIV infection is independently associated with increased cardiovascular risk.
Antiretroviral therapy contributes modestly to the risk of coronary heart disease. Antiretroviral combinations that include protease inhibitors cause the most substantial deleterious changes in lipid levels.
Most changes in lipids and insulin resistance can be managed by adding lipid-lowering and antiglycemic agents and may not require changes to the antiretroviral regimen.
Close attention to drug interactions is important when selecting lipid-lowering medications for patients on antiretroviral therapy to avoid dangerous increases in the levels of certain statins.
Addressing modifiable risk factors such as smoking, obesity, and sedentary lifestyle can have a far greater impact on cardiovascular risk than changes in antiretroviral therapy.

References

Palella FJ, Baker RK, Moorman AC, et al; HIV Outpatient Study Investigators. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr 2006; 43:27–34.
Lichtenstein KA, Armon C, Buchacz K, Moorman AC, Wood KC, Brooks JT; HOPS investigators. Analysis of cardiovascular risk factors in the HIV Outpatient Study (HOPS) cohort. Presented at the 13th Conference on Retroviruses and Opportunistic Infections; Denver, CO; 2006.
Savès M, Chêne G, Ducimetière P, et al; French WHO MONICA Project and the APROCO (ANRS EP11) Study Group. Risk factors for coronary heart disease in patients treated for human immunodeficiency virus infection compared with the general population. Clin Infect Dis 2003; 37:292–298.
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; 45:1074–1081.
Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab 2007; 92:2506–2512.
Klein D, Hurley LB, Quesenberry CP, Sidney S. Do protease inhibitors increase the risk for coronary heart disease in patients with HIV-1 infection? J Acquir Immune Defic Syndr 2002; 30:471–477.
Grunfeld C, Delaney JA, Wanke C, et al. Preclinical atherosclerosis due to HIV infection: carotid intima-medial thickness measurements from the FRAM study. AIDS 2009; 23:1841–1849.
Hulten E, Mitchell J, Scally J, Gibbs B, Villines TC. HIV positivity, protease inhibitor exposure and subclinical atherosclerosis: a systematic review and meta-analysis of observational studies. Heart 2009; 95:1826–1835.
Riddler SA, Smit E, Cole SR, et al. Impact of HIV infection and HAART on serum lipids in men. JAMA 2003; 289:2978–2982.
Shahmanesh M, Das S, Stolinski M, et al. Antiretroviral treatment reduces very-low-density lipoprotein and intermediate-density lipoprotein apolipoprotein B fractional catabolic rate in human immunodeficiency virus-infected patients with mild dyslipidemia. J Clin Endocrinol Metab 2005; 90:755–760.
Mujawar Z, Rose H, Morrow MP, et al. Human immunodeficiency virus impairs reverse cholesterol transport from macrophages. PLoS Biol 2006; 4:e365.
Park IW, Wang JF, Groopman JE. HIV-1 Tat promotes monocyte chemoattractant protein-1 secretion followed by transmigration of monocytes. Blood 2001; 97:352–358.
Fisher SD, Miller TL, Lipshultz SE. Impact of HIV and highly active antiretroviral therapy on leukocyte adhesion molecules, arterial inflammation, dyslipidemia, and atherosclerosis. Atherosclerosis 2006; 185:1–11.
Hsue PY, Hunt PW, Schnell A, et al. Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV-associated atherosclerosis. AIDS 2009; 23:1059–1067.
Currier JS, Taylor A, Boyd F, et al. Coronary heart disease in HIV-infected individuals. J Acquir Immune Defic Syndr 2003; 33:506–512.
DAD Study Group; Friis-Møller N, Reiss P, Sabin CA, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007: 356:1723–1735.
DAD Study Group; 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; 371:1417–1426.
Durand M, Sheehy O, Baril JG, Lelorier J, Tremblay C; GRUCHUM Research Center (Groupe de Recherche de l’UHRESS du Centre Hospitalier Universitaire de Montréal). Relation between use of nucleoside reverse transcriptase inhibitors (NRTI) and risk of myocardial infarction (MI): a nested case control study using Quebec’s public health insurance database (QPHID). Presented at the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention in Cape Town, South Africa, July 17–22, 2009.
Lang S, Mary-Krause M, Cotte L, et al; the Clinical Epi Group of the French Hospital Database on HIV. Impact of specific NRTI and PI exposure on the risk of myocardial infarction: a case-control study nested within FHDH ANRS CO4. Presented at the 16th Conference on Retroviruses and Opportunistic Infections in Montreal, Canada, February 8–11, 2009.
Strategies for Management of Anti-Retroviral Therapy/INSIGHT. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients. AIDS 2008; 22:F17–F24.
Bedimo R, Westfall A, Drechsler H, Tebas P. Abacavir use and risk of acute myocardial infarction and cerebrovascular disease in the HAART era. Presented at the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention in Cape Town, South Africa, July 19–22, 2009.
Brothers CH, Hernandez JE, Cutrell AG, et al. Risk of myocardial infarction and abacavir therapy: no increased risk across 52 GlaxoSmithKline-sponsored clinical trials in adult subjects. J Acquir Immune Defic Syndr 2009; 51:20–28.
Benson C, Ribaudo H, Zheng E, et al; the ACTG A5001/ALLRT Protocol Team. No Association of Abacavir Use with Risk of Myocardial Infarction or Severe Cardiovascular Disease Events: Results from ACTG A5001. Presented at the 16th Conference on Retroviruses and Opportunistic Infections in Montreal, Canada, February 8–11, 2009.
Torriani FJ, Komarow L, Parker RA, et al; ACTG 5152s Study Team. Endothelial function in human immunodeficiency virus-infected antiretroviral-naive subjects before and after starting potent antiretroviral therapy: The ACTG (AIDS Clinical Trials Group) Study 5152s. J Am Coll Cardiol 2008; 52:569–576.
Calmy A, Gayet-Ageron A, Montecucco F, et al; STACCATO Study Group. HIV increases markers of cardiovascular risk: results from a randomized, treatment interruption trial. AIDS 2009; 23:929–939.
van Vonderen MG, Hassink EA, van Agtmael MA, et al. Increase in carotid artery intima-media thickness and arterial stiffness but improvement in several markers of endothelial function after initiation of antiretroviral therapy. J Infect Dis 2009; 199:1186–1194.
Strategies for Management of Antiretroviral Therapy (SMART) Study Group; El-Sadr WM, Lundgren JD, Neaton JD, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 2006; 355:2283–2296.
Phillips AN, Carr A, Neuhaus J, et al. Interruption of antiretroviral therapy and risk of cardiovascular disease in persons with HIV-1 infection: exploratory analyses from the SMART trial. Antivir Ther 2008; 13:177–187.
Kuller LH, Tracy R, Belloso WINSIGHT SMART Study Group. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med 2008; 5:e203.
Badiou S, De Boever CM, Dupuy AM, Baillat V, Cristol JP, Reynes J. Small dense LDL and atherogenic lipid profile in HIV-positive adults: influence of lopinavir/ritonavir-containing regimen. AIDS 2003; 17:772–774.
Duong M, Petit JM, Martha B, et al. Concentration of circulating oxidized LDL in HIV-infected patients treated with antiretroviral agents: relation to HIV-related lipodystrophy. HIV Clin Trials 2006; 7:41–47.
Fisac C, Fumero E, Crespo M, et al. Metabolic benefits 24 months after replacing a protease inhibitor with abacavir, efavirenz or nevirapine. AIDS 2005; 19:917–925.
Hicks CB, Cahn P, Cooper DA, et al; RESIST investigator group. Durable efficacy of tipranavir-ritonavir in combination with an optimised background regimen of antiretroviral drugs for treatmentexperienced HIV-1-infected patients at 48 weeks in the Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST) studies: an analysis of combined data from two randomised open-label trials. Lancet 2006; 368:466–475.
Malan DR, Krantz E, David N, Wirtz V, Hammond J, McGrath D; 089 Study Group. Efficacy and safety of atazanavir, with or without ritonavir, as part of once-daily highly active antiretroviral therapy regimens in antiretroviral-naive patients. J Acquir Immune Defic Syndr 2008; 47:161–167.
Anastos K, Lu D, Shi Q, et al. Association of serum lipid levels with HIV serostatus, specific antiretroviral agents, and treatment regimens. J Acquir Immune Defic Syndr 2007; 45:34–42.
Tomaka F, Lefebvre E, Sekar V, et al. Effects of ritonavir-boosted darunavir vs ritonavir-boosted atazanavir on lipid and glucose parameters in HIV-negative, healthy volunteers. HIV Med 2009; 10:318–327.
Eron J, Yeni P, Gathe J, et al; KLEAN study team. 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. Lancet 2006; 368:476–482.
Shafran SD, Mashinter LD, Roberts SE. The effect of low-dose ritonavir monotherapy on fasting serum lipid concentrations. HIV Med 2005; 6:421–425.
Kumar PN, Rodriguez-French A, Thompson MA, et al; ESS40002 Study Team. A prospective, 96-week study of the impact of trizivir, combivir/nelfinavir, and lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in antiretroviral-naive patients: effect of sex and ethnicity. HIV Med 2006; 7:85–98.
Shafran SD, Mashinter LD, Roberts SE. The effect of low-dose ritonavir monotherapy on fasting serum lipid concentrations. HIV Med 2005; 6:421–425.
Walmsley S, Avihingsanon A, Slim J, et al. Gemini: a noninferiority study of saquinavir/ritonavir versus lopinavir/ritonavir as initial HIV-1 therapy in adults. J Acquir Immune Defic Syndr 2009; 50:367–374.
DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents— A Working Group of the Office of AIDS Research Advisory Council (OARAC). Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. December 1, 1009. http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed June 29, 2010.
Shikuma CM, Yang Y, Glesby MJ, et al. Metabolic effects of protease inhibitor-sparing antiretroviral regimens given as initial treatment of HIV-1 Infection (AIDS Clinical Trials Group Study A5095). J Acquir Immune Defic Syndr 2007; 44:540–550.
van Leth F, Phanuphak P, Stroes E, et al. Nevirapine and efavirenz elicit different changes in lipid profiles in antiretroviral-therapynaive patients infected with HIV-1. PLoS Med 2004; 1:e19.
Katlama C, Haubrich R, Lalezari J, et al; DUET-1, DUET-2 study groups. Efficacy and safety of etravirine in treatment-experienced, HIV-1 patients: pooled 48 week analysis of two randomized, controlled trials. AIDS 2009; 23:2289–2300.
Hammond E, Nolan D, James I, Metcalf C, Mallal S. Reduction of mitochondrial DNA content and respiratory chain activity occurs in adipocytes within 6–12 months of commencing nucleoside reverse transcriptase inhibitor therapy. AIDS 2004; 18:815–817.
Pozniak AL, Gallant JE, DeJesus E, et al. Tenofovir disoproxil fumarate, emtricitabine, and efavirenz versus fixed-dose zidovudine/lamivudine and efavirenz in antiretroviral-naive patients: virologic, immunologic, and morphologic changes—a 96-week analysis. J Acquir Immune Defic Syndr 2006; 43:535–540.
Tungsiripat M, Kitch D, Glesby M, et al. A pilot study to determine the effect on dyslipidemia of the addition of tenofovir to stable background ART in HIV-infected subjects: results from the A5206 Study Team. Presented at the 16th Conference on Retroviruses and Opportunistic Infections in Montreal, Canada, February 8–11, 2009.
Law MG, Friis-Møller N, El-Sadr WM, et al; D:A:D Study Group. The use of the Framingham equation to predict myocardial infarctions in HIV-infected patients: comparison with observed events in the D:A:D Study. HIV Med 2006; 7:218–230.
Aberg JA. Cardiovascular complications in HIV management: past, present, and future. J Acquir Immune Defic Syndr 2009; 50:54–64.
Dubé MP, Stein JH, Aberg JA, et al; Adult AIDS Clinical Trials Group Cardiovascular Subcommittee. 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; 37:613–627.
Fichtenbaum CJ. Metabolic abnormalities associated with HIV infection and antiretroviral therapy. Curr Infect Dis Rep 2009; 11:84–92.
Gerber JG, Rosenkranz SL, Fichtenbaum CJ, et al; AIDS Clinical Trials Group A5108 Team. Effect of efavirenz on the pharmacokinetics of simvastatin, atorvastatin, and pravastatin: results of AIDS Clinical Trials Group 5108 Study. J Acquir Immune Defic Syndr 2005; 39:307–312.
Grennan T, Walmsley S. Etravirine for HIV-I: addressing the limitations of the nonnucleoside reverse transcriptase inhibitor class. J Int Assoc Physicians AIDS Care (Chic Ill) 2009; 8:354–363.
Sekar V S-GS, Marien K. Pharmacokinetic drug-drug interaction between the new HIV protease inhibitor darunavir (TMC114) and the lipid-lowering agent pravastatin. Presented at the 8th International Workshop on Pharmacology of HIV Therapy; Budapest, Hungary, April 16–18, 2007.
Kiser JJ, Gerber JG, Predhomme JA, Wolfe P, Flynn DM, Hoody DW. Drug/drug interaction between lopinavir/ritonavir and rosuvastatin in healthy volunteers. J Acquir Immune Defic Syndr 2008; 47:570–578.
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; 24:77–83.
Chow D, Chen H, Glesby MJ, et al. Short-term ezetimibe is well tolerated and effective in combination with statin therapy to treat elevated LDL cholesterol in HIV-infected patients. AIDS 2009; 23:2133–2141.
Aberg JA, Zackin RA, Brobst SW, et al; ACTG 5087 Study Team. 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; 21:757–767.
Dubé MP, Wu JW, Aberg JA, et al; AIDS Clinical Trials Group A5148 Study Team. Safety and efficacy of extended-release niacin for the treatment of dyslipidaemia in patients with HIV infection: AIDS Clinical Trials Group Study A5148. Antivir Ther 2006; 11:1081–1089.
Gerber JG, Kitch DW, Fichtenbaum CJ, et al. Fish oil and fenofibrate for the treatment of hypertriglyceridemia in HIV-infected subjects on antiretroviral therapy: results of ACTG A5186. J Acquir Immune Defic Syndr 2008; 47:459–466.
Mallolas J, Podzamczer D, Milinkovic A, et al; ATAZIP Study Group. Efficacy and safety of switching from boosted lopinavir to boosted atazanavir in patients with virological suppression receiving a LPV/rcontaining HAART: the ATAZIP study. J Acquir Immune Defic Syndr 2009; 51:29–36.
Eron J, Andrade J, Zajdenverg R, et al. Switching from stable lopinavir/ritonavir-based to raltegravir-based combination ART resulted in a superior lipid profile at week 12 but did not demonstrate noninferior virologic efficacy at week 24. Presented at the 16th Conference on Retroviruses and Opportunistic Infections in Montreal, Canada, February 8–11, 2009.
Calza L, Manfredi R, Colangeli V, et al. Substitution of nevirapine or efavirenz for protease inhibitor versus lipid-lowering therapy for the management of dyslipidaemia. AIDS 2005; 19:1051–1058.
Worm SW, De Wit S, Weber R, et al. Diabetes mellitus, preexisting coronary heart disease, and the risk of subsequent coronary heart disease events in patients infected with human immunodeficiency virus: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D Study). Circulation 2009; 119:805–811.
Brown TT, Cole SR, Li X, et al. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study. Arch Intern Med 2005; 165:1179–1184.
Butt AA, McGinnis K, Rodriguez-Barradas MC, et al; Veterans Aging Cohort Study. HIV infection and the risk of diabetes mellitus. AIDS 2009; 23:1227–1234.
Mulligan K, Yang Y, Wininger DA, et al. Effects of metformin and rosiglitazone in HIV-infected patients with hyperinsulinemia and elevated waist/hip ratio. AIDS 2007; 21:47–57.

Widespread use of antiretroviral therapy has caused a remarkable decline in rates of morbidity and death related to acquired immunodeficiency syndrome (AIDS) and has effectively made human immunodeficiency virus (HIV) infection a manageable—although not yet curable— chronic condition. And as the HIV-infected population on antiretroviral therapy ages, the prevalence of chronic conditions (eg, cardiovascular disease, hepatic disease, pulmonary disease, non-AIDS cancers) and deaths attributable to these conditions have also increased. ¹

Many of the traditional risk factors for cardiovascular disease in the general population, including smoking, dyslipidemia, and diabetes, are common in HIV-infected patients, and HIV infection itself independently increases the risk of coronary heart disease. In addition, different antiretroviral combinations can contribute, in varying degrees, to changes in lipid levels and insulin resistance, further increasing coronary risk.

Ultimately, however, the immunologic benefits of antiretroviral therapy for individual patients far exceed the modest increase in cardiovascular risk associated with certain regimens. In most cases, careful selection of the initial antiretroviral regimen and the addition of lipid-lowering or glucose-controlling medications (with close attention to drug interactions) can effectively manage the metabolic changes associated with antiretroviral therapy and obviate any premature modification of virologically suppressive regimens.

TRADITIONAL CARDIAC RISK FACTORS IN HIV PATIENTS

The risk of coronary heart disease in HIV patients is influenced mostly by traditional factors such as age, smoking, diabetes, and dyslipidemia, including high levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C) and low levels of high-density lipoprotein cholesterol (HDL-C). ²

In various large cohorts, HIV-infected men had a higher prevalence of smoking, ³ a lower mean HDL-C level, ^3,4 and a higher mean triglyceride level ^3,4 than men without HIV infection, placing them at greater risk of coronary heart disease. However, even after adjusting for traditional risk factors, rates of atherosclerosis are still higher in people who are infected with HIV than in those who are not. ⁵

EFFECT OF HIV INFECTION ON CORONARY RISK

HIV infection has been shown to increase coronary risk.

In the Kaiser Permanente database, ⁶ HIV-positive patients had a significantly higher rate of hospitalizations for coronary heart disease than did people who were not infected.

Similarly, in a cohort study of almost 4,000 HIV-infected patients and more than 1 million controls, the risk of acute myocardial infarction was 75% higher for HIV-positive patients than for HIV-negative patients, even after adjusting for sex, race, hypertension, diabetes, and dyslipidemia. ⁵

The Fat Redistribution and Metabolism (FRAM) cross-sectional study ⁷ showed that HIV infection was associated with greater carotid intima media thickness, an established marker of atherosclerosis, independently of traditional risk factors and to virtually the same degree as smoking and male sex.

Other studies of subclinical atherosclerosis in HIV patients have yielded disparate results, likely because of differences in study design, methods of measuring carotid thickness, and characteristics of the study populations (eg, prevalence of cardiovascular risk factors and stage of HIV disease). However, a meta-analysis of six prospective cohort studies, three case-control studies, and four cross-sectional studies confirmed that HIV patients had slightly but statistically significantly greater carotid intima media thickness than HIV-negative people. ⁸

References

Palella FJ, Baker RK, Moorman AC, et al; HIV Outpatient Study Investigators. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr 2006; 43:27–34.
Lichtenstein KA, Armon C, Buchacz K, Moorman AC, Wood KC, Brooks JT; HOPS investigators. Analysis of cardiovascular risk factors in the HIV Outpatient Study (HOPS) cohort. Presented at the 13th Conference on Retroviruses and Opportunistic Infections; Denver, CO; 2006.
Savès M, Chêne G, Ducimetière P, et al; French WHO MONICA Project and the APROCO (ANRS EP11) Study Group. Risk factors for coronary heart disease in patients treated for human immunodeficiency virus infection compared with the general population. Clin Infect Dis 2003; 37:292–298.
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; 45:1074–1081.
Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab 2007; 92:2506–2512.
Klein D, Hurley LB, Quesenberry CP, Sidney S. Do protease inhibitors increase the risk for coronary heart disease in patients with HIV-1 infection? J Acquir Immune Defic Syndr 2002; 30:471–477.
Grunfeld C, Delaney JA, Wanke C, et al. Preclinical atherosclerosis due to HIV infection: carotid intima-medial thickness measurements from the FRAM study. AIDS 2009; 23:1841–1849.
Hulten E, Mitchell J, Scally J, Gibbs B, Villines TC. HIV positivity, protease inhibitor exposure and subclinical atherosclerosis: a systematic review and meta-analysis of observational studies. Heart 2009; 95:1826–1835.
Riddler SA, Smit E, Cole SR, et al. Impact of HIV infection and HAART on serum lipids in men. JAMA 2003; 289:2978–2982.
Shahmanesh M, Das S, Stolinski M, et al. Antiretroviral treatment reduces very-low-density lipoprotein and intermediate-density lipoprotein apolipoprotein B fractional catabolic rate in human immunodeficiency virus-infected patients with mild dyslipidemia. J Clin Endocrinol Metab 2005; 90:755–760.
Mujawar Z, Rose H, Morrow MP, et al. Human immunodeficiency virus impairs reverse cholesterol transport from macrophages. PLoS Biol 2006; 4:e365.
Park IW, Wang JF, Groopman JE. HIV-1 Tat promotes monocyte chemoattractant protein-1 secretion followed by transmigration of monocytes. Blood 2001; 97:352–358.
Fisher SD, Miller TL, Lipshultz SE. Impact of HIV and highly active antiretroviral therapy on leukocyte adhesion molecules, arterial inflammation, dyslipidemia, and atherosclerosis. Atherosclerosis 2006; 185:1–11.
Hsue PY, Hunt PW, Schnell A, et al. Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV-associated atherosclerosis. AIDS 2009; 23:1059–1067.
Currier JS, Taylor A, Boyd F, et al. Coronary heart disease in HIV-infected individuals. J Acquir Immune Defic Syndr 2003; 33:506–512.
DAD Study Group; Friis-Møller N, Reiss P, Sabin CA, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007: 356:1723–1735.
DAD Study Group; 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; 371:1417–1426.
Durand M, Sheehy O, Baril JG, Lelorier J, Tremblay C; GRUCHUM Research Center (Groupe de Recherche de l’UHRESS du Centre Hospitalier Universitaire de Montréal). Relation between use of nucleoside reverse transcriptase inhibitors (NRTI) and risk of myocardial infarction (MI): a nested case control study using Quebec’s public health insurance database (QPHID). Presented at the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention in Cape Town, South Africa, July 17–22, 2009.
Lang S, Mary-Krause M, Cotte L, et al; the Clinical Epi Group of the French Hospital Database on HIV. Impact of specific NRTI and PI exposure on the risk of myocardial infarction: a case-control study nested within FHDH ANRS CO4. Presented at the 16th Conference on Retroviruses and Opportunistic Infections in Montreal, Canada, February 8–11, 2009.
Strategies for Management of Anti-Retroviral Therapy/INSIGHT. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients. AIDS 2008; 22:F17–F24.
Bedimo R, Westfall A, Drechsler H, Tebas P. Abacavir use and risk of acute myocardial infarction and cerebrovascular disease in the HAART era. Presented at the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention in Cape Town, South Africa, July 19–22, 2009.
Brothers CH, Hernandez JE, Cutrell AG, et al. Risk of myocardial infarction and abacavir therapy: no increased risk across 52 GlaxoSmithKline-sponsored clinical trials in adult subjects. J Acquir Immune Defic Syndr 2009; 51:20–28.
Benson C, Ribaudo H, Zheng E, et al; the ACTG A5001/ALLRT Protocol Team. No Association of Abacavir Use with Risk of Myocardial Infarction or Severe Cardiovascular Disease Events: Results from ACTG A5001. Presented at the 16th Conference on Retroviruses and Opportunistic Infections in Montreal, Canada, February 8–11, 2009.
Torriani FJ, Komarow L, Parker RA, et al; ACTG 5152s Study Team. Endothelial function in human immunodeficiency virus-infected antiretroviral-naive subjects before and after starting potent antiretroviral therapy: The ACTG (AIDS Clinical Trials Group) Study 5152s. J Am Coll Cardiol 2008; 52:569–576.
Calmy A, Gayet-Ageron A, Montecucco F, et al; STACCATO Study Group. HIV increases markers of cardiovascular risk: results from a randomized, treatment interruption trial. AIDS 2009; 23:929–939.
van Vonderen MG, Hassink EA, van Agtmael MA, et al. Increase in carotid artery intima-media thickness and arterial stiffness but improvement in several markers of endothelial function after initiation of antiretroviral therapy. J Infect Dis 2009; 199:1186–1194.
Strategies for Management of Antiretroviral Therapy (SMART) Study Group; El-Sadr WM, Lundgren JD, Neaton JD, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 2006; 355:2283–2296.
Phillips AN, Carr A, Neuhaus J, et al. Interruption of antiretroviral therapy and risk of cardiovascular disease in persons with HIV-1 infection: exploratory analyses from the SMART trial. Antivir Ther 2008; 13:177–187.
Kuller LH, Tracy R, Belloso WINSIGHT SMART Study Group. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med 2008; 5:e203.
Badiou S, De Boever CM, Dupuy AM, Baillat V, Cristol JP, Reynes J. Small dense LDL and atherogenic lipid profile in HIV-positive adults: influence of lopinavir/ritonavir-containing regimen. AIDS 2003; 17:772–774.
Duong M, Petit JM, Martha B, et al. Concentration of circulating oxidized LDL in HIV-infected patients treated with antiretroviral agents: relation to HIV-related lipodystrophy. HIV Clin Trials 2006; 7:41–47.
Fisac C, Fumero E, Crespo M, et al. Metabolic benefits 24 months after replacing a protease inhibitor with abacavir, efavirenz or nevirapine. AIDS 2005; 19:917–925.
Hicks CB, Cahn P, Cooper DA, et al; RESIST investigator group. Durable efficacy of tipranavir-ritonavir in combination with an optimised background regimen of antiretroviral drugs for treatmentexperienced HIV-1-infected patients at 48 weeks in the Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST) studies: an analysis of combined data from two randomised open-label trials. Lancet 2006; 368:466–475.
Malan DR, Krantz E, David N, Wirtz V, Hammond J, McGrath D; 089 Study Group. Efficacy and safety of atazanavir, with or without ritonavir, as part of once-daily highly active antiretroviral therapy regimens in antiretroviral-naive patients. J Acquir Immune Defic Syndr 2008; 47:161–167.
Anastos K, Lu D, Shi Q, et al. Association of serum lipid levels with HIV serostatus, specific antiretroviral agents, and treatment regimens. J Acquir Immune Defic Syndr 2007; 45:34–42.
Tomaka F, Lefebvre E, Sekar V, et al. Effects of ritonavir-boosted darunavir vs ritonavir-boosted atazanavir on lipid and glucose parameters in HIV-negative, healthy volunteers. HIV Med 2009; 10:318–327.
Eron J, Yeni P, Gathe J, et al; KLEAN study team. 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. Lancet 2006; 368:476–482.
Shafran SD, Mashinter LD, Roberts SE. The effect of low-dose ritonavir monotherapy on fasting serum lipid concentrations. HIV Med 2005; 6:421–425.
Kumar PN, Rodriguez-French A, Thompson MA, et al; ESS40002 Study Team. A prospective, 96-week study of the impact of trizivir, combivir/nelfinavir, and lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in antiretroviral-naive patients: effect of sex and ethnicity. HIV Med 2006; 7:85–98.
Shafran SD, Mashinter LD, Roberts SE. The effect of low-dose ritonavir monotherapy on fasting serum lipid concentrations. HIV Med 2005; 6:421–425.
Walmsley S, Avihingsanon A, Slim J, et al. Gemini: a noninferiority study of saquinavir/ritonavir versus lopinavir/ritonavir as initial HIV-1 therapy in adults. J Acquir Immune Defic Syndr 2009; 50:367–374.
DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents— A Working Group of the Office of AIDS Research Advisory Council (OARAC). Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. December 1, 1009. http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed June 29, 2010.
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Coronary heart disease in people infected with HIV

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