Risk of Cardiovascular Disease in an Aging HIV Population: Where Are We Now?

Current HIV/AIDS Reports

Volumn 12, Issue 4, 2015, Pages 375-387

  Martin Iguacel, R ^a   Llibre, J M ^b,c   Friis Moller, N ^a  

^a ODENSE UNIVERSITY HOSPITAL   (Denmark)

^b HOSPITAL UNIVERSITARI GERMANS TRIAS I PUJOL   (Spain)

^c UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

Author keywords

Acute myocardial infarction; Antiretroviral therapy; Cardiovascular Risk; Cerebrovascular disease; HIV

Indexed keywords

ABACAVIR; ANTIRETROVIRUS AGENT; CHOLESTEROL; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HUMAN IMMUNODEFICIENCY VIRUS PROTEINASE INHIBITOR; INTEGRASE INHIBITOR; LOW DENSITY LIPOPROTEIN CHOLESTEROL; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; RNA DIRECTED DNA POLYMERASE INHIBITOR; TRIACYLGLYCEROL;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ACUTE HEART INFARCTION; AGING; ARTERIAL WALL THICKNESS; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CD4 LYMPHOCYTE COUNT; CHOLESTEROL BLOOD LEVEL; CHRONIC INFLAMMATION; DRUG CHOICE; DRUG EFFICACY; DRUG EXPOSURE; DRUG SAFETY; FOLLOW UP; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERTENSION; IMMUNE RESPONSE; IMMUNOPATHOLOGY; LIFESTYLE MODIFICATION; METABOLIC DISORDER; MORBIDITY; MORTALITY; OUTCOME ASSESSMENT; PATHOGENESIS; PLATELET REACTIVITY; PRIMARY PREVENTION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK ASSESSMENT; RISK BENEFIT ANALYSIS; RISK REDUCTION; SECONDARY PREVENTION; SMOKING; SMOKING CESSATION; THROMBOSIS; CARDIOVASCULAR DISEASES; COMPLICATION; EUROPE; HIV INFECTIONS; RISK FACTOR; UNITED STATES;

AGING; CARDIOVASCULAR DISEASES; EUROPE; HIV INFECTIONS; HUMANS; RISK FACTORS; UNITED STATES;

EID: 84947017147     PISSN: 15483568     EISSN: 15483576     Source Type: Journal    
DOI: 10.1007/s11904-015-0284-6     Document Type: Review

References (118)

1. Palella FJ, Baker RK, Moorman AC, Chmiel JS, Wood KC, Brooks JT, et al. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. JAIDS J Acquir Immune Defic Syndr. 2006;43:27–34.
2. Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, et al. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet. 2014;384:241–8.
3. Samji H, Cescon A, Hogg RS, Modur SP, Althoff KN, Buchacz K, et al. Closing the gap: increases in life expectancy among treated HIV-positive individuals in the United States and Canada. Okulicz JF, editor. PLoS ONE. 2013;8:e81355.
4. Klein D, Hurley LB, Quesenberry CP, Sidney S. Do protease inhibitors increase the risk for coronary heart disease in patients with HIV-1 infection? JAIDS J Acquir Immune Defic Syndr. 2002;30:471–7.
5. Currier JS, Taylor A, Boyd F, Dezii CM, Kawabata H, Burtcel B, et al. Coronary heart disease in HIV-infected individuals. JAIDS J Acquir Immune Defic Syndr. 2003;33:506–12.
6. Mary-Krause M, Cotte L, Simon A, Partisani M, Costagliola D, Clinical Epidemiology Group from the French Hospital Database. Increased risk of myocardial infarction with duration of protease inhibitor therapy in HIV-infected men. AIDS. 2003;17:2479–86.
7. 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 [Internet]. 2007;92:2506–12. Available from: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=17456578&retmode=ref&cmd=prlinks
8. Obel N, Thomsen HF, Kronborg G, Larsen CS, Hildebrandt PR, Sørensen HT, et al. Ischemic heart disease in HIV-infected and HIV-uninfected individuals: a population-based cohort study. Clin Infect Dis. 2007;44:1625–31.
9. Lang S, Mary-Krause M, Cotte L, Gilquin J, Partisani M, Simon A, et al. Increased risk of myocardial infarction in HIV-infected patients in France, relative to the general population. AIDS. 2010;24:1228–30.
10. Durand M, Sheehy O, Baril J-G, Lelorier J, Tremblay CL. Association between HIV infection, antiretroviral therapy, and risk of acute myocardial infarction: a cohort and nested case–control study using Québec’s public health insurance database. J Acquir Immune Defic Syndr. 2011;57:245–53.
11. Freiberg MS, Chang C-CH, Kuller LH, Skanderson M, Lowy E, Kraemer KL, et al. HIV infection and the risk of acute myocardial infarction. JAMA Intern Med. 2013;173:614. This study from the Veterans Aging Cohort Study (VACS) virtual cohort, reported a hazard ratio (HR) for MI of HR 1.48 (95% CI 1.27-1.72) after adjusting for Framingham risk factors, comorbid diseases and substance abuse. Notably, the CV risk persisted in patients achieving HIV RNA levels < than 500 c/ml (HR 1.39, 95% CI, 1.17-1.66).
12. Silverberg MJ, Leyden WA, Xu L, Horberg MA, Chao CR, Towner WJ, et al. Immunodeficiency and risk of myocardial infarction among HIV-positive individuals with access to care. J Acquir Immune Defic Syndr. 2014;65:160–6. This study from the Kaiser group reported a RR of AMI of 1.44 (95% CI, 1.27-1.64), after adjusting for tradicional CVD risk factors. Interestingly, the rates of MI were similar in both groups when the analysis was restricted to HIV-infected patients with recent or nadir CD4 cell count ≥ 500 c/ml (RR 0.85, 95% CI 0.55-1.33).
13. Klein DB, Leyden WA, Xu L, Chao CR, Horberg MA, Towner WJ, et al. Declining relative risk for myocardial infarction among HIV-positive compared with HIV-negative individuals with access to care. Clin Infect Dis. 2015. This study from the Kaiser group, assessed MI risk in HIV individuals by calendar era form 1996 to 2011 and found that there was no longer an elevated risk for MI among the HIV individuals compared to matched HIV uninfected subjects in the latest period from 2010 to 2011 (adjusted RR 1.0, 95% CI, 1.07-1.4). They report that the CV risk profile for both groups were similar in this period, even more favorable in the HIV positive group.
14. Paisible A-L, Chang C-CH, So-Armah KA, Butt AA, Leaf DA, Budoff M, et al. HIV infection, cardiovascular disease risk factor profile, and risk for acute myocardial infarction. J Acquir Immune Defic Syndr. 2015;68:209–16.
15. Butt AA, Chang C-C, Kuller L, Goetz MB, Leaf D, Rimland D, et al. Risk of heart failure with human immunodeficiency virus in the absence of prior diagnosis of coronary heart disease. Arch Intern Med. 2011;171:737–43.
16. Sico JJ, Chang C-CH, So-Armah K, Justice AC, Hylek E, Skanderson M, et al. HIV status and the risk of ischemic stroke among men. Neurology. 2015;84:1933–40.
17. Tseng ZH, Secemsky EA, Dowdy D, Vittinghoff E, Moyers B, Wong JK, et al. Sudden cardiac death in patients with human immunodeficiency virus infection. J Am Coll Cardiol. Elsevier Inc; 2012;59:1891–6.
18. Islam FM, Wu J, Jansson J, Wilson DP. Relative risk of cardiovascular disease among people living with HIV: a systematic review and meta-analysis. HIV Med. 2012;:n/a–n/a.
19. Abd-Elmoniem KZ, Unsal AB, Eshera S, Matta JR, Muldoon N, McAreavey D, et al. Increased coronary vessel wall thickness in HIV-infected young adults. Clin Infect Dis. 2014;59:1779–86.
20. Post WS, Budoff M, Kingsley L, Palella FJ, Witt MD, Li X, et al. Associations between HIV infection and subclinical coronary atherosclerosis. Ann Intern Med. 2014;160:458–67.
21. Lo J, Abbara S, Shturman L, Soni A, Wei J, Rocha-Filho JA, et al. Increased prevalence of subclinical coronary atherosclerosis detected by coronary computed tomography angiography in HIV-infected men. AIDS. 2010;24:243–53.
22. Freitas P, Carvalho D, Santos AC, Madureira AJ, Martinez E, Pereira J, et al. Carotid intima media thickness is associated with body fat abnormalities in HIV-infected patients. BMC Infect Dis. 2014;14:348.
23. Grunfeld C, Delaney JA, Wanke C, Currier JS, Scherzer R, Biggs ML, et al. Preclinical atherosclerosis due to HIV infection: carotid intima-medial thickness measurements from the FRAM study. AIDS. 2009;23:1841–9.
24. Chanthong P, Lapphra K, Saihongthong S, Sricharoenchai S, Wittawatmongkol O, Phongsamart W, et al. Echocardiography and carotid intima–media thickness among asymptomatic HIV-infected adolescents in Thailand. AIDS. 2014;28:2071–9.
25. Hsue PY, Hunt PW, Schnell A, Kalapus SC, Hoh R, Ganz P, et al. Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV-associated atherosclerosis. AIDS. 2009;23:1059–67.
26. Pereyra F, Lo J, Triant VA, Wei J, Buzon MJ, Fitch KV, et al. Increased coronary atherosclerosis and immune activation in HIV-1 elite controllers. AIDS. 2012;26:2409–12.
27. Teo KK, Ounpuu S, Hawken S, Pandey MR, Valentin V, Hunt D, et al. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case–control study. Lancet. 2006;368:647–58.
28. Friis-Møller N, Weber R, Reiss P, Thiébaut R, Kirk O, d’Arminio Monforte A, et al. Cardiovascular disease risk factors in HIV patients—association with antiretroviral therapy. Results from the DAD study. AIDS. 2003;17:1179–93.
29. Rasmussen LD, Helleberg M, May MT, Afzal S, Kronborg G, Larsen CS, et al. Myocardial infarction among danish HIV-infected individuals: population-attributable fractions associated with smoking. Clin Infect Dis. 2015. In this study a population-based nationwide HIV cohort (Danish HIV Cohort Study) was compared to a matched background population and found that cigarette smoking in the HIV-population was associated with a higher risk of MI compared to the general population.
30. Helleberg M, Afzal S, Kronborg G, Larsen CS, Pedersen G, Pedersen C, et al. Mortality attributable to smoking among HIV-1-infected individuals: a nationwide, population-based cohort study. Clin Infect Dis. 2013;56:727–34. In this study the Danish HIV cohort was compared to a matched background population and found that the loss of life-years associated with smoking was larger than that associated with HIV. Besides, the population-attributable risk of death associated with smoking was doubled in the HIV population compared to the general population.
31. Petoumenos K, Worm S, Reiss P, De Wit S, d’Arminio Monforte A, Sabin C, et al. Rates of cardiovascular disease following smoking cessation in patients with HIV infection: results from the D:A:D study*. HIV Med. 2011;12:412–21. Analysis from the D:A:D study found that the risk of CVD in the HIV-population decreased with increasing time since stopping smoking. These results highlight the importance of the effort to motivate smoking cessation in this population.
32. Baekken M, Os I, Sandvik L, Oektedalen O. Hypertension in an urban HIV-positive population compared with the general population: influence of combination antiretroviral therapy. J Hypertens. 2008;26:2126–33.
33. Thiébaut R, El-Sadr WM, Friis-Møller N, Rickenbach M, Reiss P, Monforte AD, et al. Predictors of hypertension and changes of blood pressure in HIV-infected patients. Antivir Ther. 2005;10:811–23.
34. Palacios R, Santos J, García A, Castells E, González M, Ruiz J, et al. Impact of highly active antiretroviral therapy on blood pressure in HIV-infected patients. A prospective study in a cohort of naive patients. HIV Med. 2006;7:10–5.
35. Crane HM, Van Rompaey SE, Kitahata MM. Antiretroviral medications associated with elevated blood pressure among patients receiving highly active antiretroviral therapy. AIDS. 2006;20:1019–26.
36. Seaberg EC, Muñoz A, Lu M, Detels R, Margolick JB, Riddler SA, et al. Association between highly active antiretroviral therapy and hypertension in a large cohort of men followed from 1984 to 2003. AIDS. 2005;19:953–60.
37. Worm SW, De Wit S, Weber R, Sabin CA, Reiss P, El-Sadr W, 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;119:805–11.
38. Brown TT, Cole SR, Li X, Kingsley LA, Palella FJ, Riddler SA, et al. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study. Arch Intern Med. 2005;165:1179–84.
39. Rasmussen LD, Mathiesen ER, Kronborg G, Pedersen C, Gerstoft J, Obel N. Risk of diabetes mellitus in persons with and without HIV: a Danish nationwide population-based cohort study. Atashili J, editor. PLoS ONE. 2012;7:e44575.
40. De Wit S, Sabin CA, Weber R, Worm SW, Reiss P, Cazanave C, et al. Incidence and risk factors for new-onset diabetes in HIV-infected patients: the data collection on adverse events of anti-HIV drugs (D:A:D) study. Diabetes Care. 2008;31:1224–9.
41. Ledergerber B, Furrer H, Rickenbach M, Lehmann R, Elzi L, Hirschel B, et al. Factors associated with the incidence of type 2 diabetes mellitus in HIV-infected participants in the Swiss HIV cohort study. Clin Infect Dis. 2007;45:111–9.
42. Friis-Møller N, Sabin CA, Weber R, d’Arminio Monforte A, El-Sadr WM, Reiss P, et al. Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med. 2003;349:1993–2003.
43. D:A:D study group, Friis-Møller N, Reiss P, Sabin CA, Weber R, Monforte AD, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med. 2007;356:1723–35. This study from the D:A:D study group was one of the first studies to describe the excess risk of CVD in patients treated with ART.
44. Worm SW, Sabin C, Weber R, Reiss P, El-Sadr W, Dabis F, 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;201:318–30.
45. Holmberg SD, Moorman AC, Williamson JM, Tong TC, Ward DJ, Wood KC, et al. Protease inhibitors and cardiovascular outcomes in patients with HIV-1. Lancet. 2002;360:1747–8.
46. Iloeje UH, Yuan Y, L’italien G, Mauskopf J, Holmberg SD, Moorman AC, et al. Protease inhibitor exposure and increased risk of cardiovascular disease in HIV-infected patients. HIV Med. 2005;6:37–44.
47. Lang S, Mary-Krause M, Cotte L, Gilquin J, Partisani M, Simon A, et al. Impact of individual antiretroviral drugs on the risk of myocardial infarction in human immunodeficiency virus-infected patients: a case–control study nested within the French Hospital Database on HIV ANRS cohort CO4. Arch Intern Med. 2010;170:1228–38.
48. Brothers CH, Hernandez JE, Cutrell AG, Curtis L, Ait-Khaled M, Bowlin SJ, et al. Risk of myocardial infarction and abacavir therapy: no increased risk across 52 GlaxoSmithKline-sponsored clinical trials in adult subjects. JAIDS J Acquir Immune Defic Syndr. 2009;51:20–8.
49. Obel N, Farkas DK, Kronborg G, Larsen CS, Pedersen G, Riis A, et al. Abacavir and risk of myocardial infarction in HIV-infected patients on highly active antiretroviral therapy: a population-based nationwide cohort study. HIV Med. 2010;11:130–6.
50. Strategies for Management of Antiretroviral Therapy (SMART) Study Group, El-Sadr WM, Lundgren JD, Neaton JD, Gordin F, Abrams D, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355:2283–96.
51. SMART Study Group, El-Sadr WM, Grund B, Neuhaus J, Babiker A, Cohen CJ, et al. Risk for opportunistic disease and death after reinitiating continuous antiretroviral therapy in patients with HIV previously receiving episodic therapy: a randomized trial. Ann Intern Med. 2008;149:289–99.
52. Monforte AD, Reiss P, Ryom L, El-Sadr W, Dabis F, De Wit S, et al. Atazanavir is not associated with an increased risk of cardio or cerebrovascular disease events. AIDS. 2013;27:407–15.
53. D:A:D study group, Sabin CA, Worm SW, Weber R, Reiss P, El-Sadr W, 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;371:1417–26.
54. 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:F17–24.
55. Martin A, Bloch M, Amin J, Baker D, Cooper DA, Emery S, et al. Simplification of antiretroviral therapy with tenofovir‐emtricitabine or abacavir‐lamivudine: a randomized, 96‐week trial. Clin Infect Dis. 2009;49:1591–601.
56. Choi AI, Vittinghoff E, Deeks SG, Weekley CC, Li Y, Shlipak MG. Cardiovascular risks associated with abacavir and tenofovir exposure in HIV-infected persons. AIDS. 2011;25:1289–98.
57. Ribaudo HJ, Benson CA, Zheng Y, Koletar SL, Collier AC, Lok JJ, 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 [Internet]. 2011;52:929–40. Available from: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=21427402&retmode=ref&cmd=prlinks.
58. Bedimo RJ, Westfall AO, Drechsler H, Vidiella G, Tebas P. Abacavir use and risk of acute myocardial infarction and cerebrovascular events in the highly active antiretroviral therapy era. Clin Infect Dis. 2011;53:84–91.
59. Cruciani M, Zanichelli V, Serpelloni G, Bosco O, Malena M, Mazzi R, et al. Abacavir use and cardiovascular disease events. AIDS. 2011;25:1993–2004.
60. Ding X, Andraca-Carrera E, Cooper C, Miele P, Kornegay C, Soukup M, et al. No association of abacavir use with myocardial infarction: findings of an FDA meta-analysis. J Acquir Immune Defic Syndr. 2012;61:441–7.
61. Sabin C. Abacavir and increased risk of myocardial infarction. Lancet. 2008;372:803. authorreply804–5.
62. Palella FJ, Althoff KN, Moore RD. Abacavir use and risk for myocardial infarction in the NA-ACCORD. Abstract 749 LB. 22nd Conference on Retroviruses and Opportunistic Infections (CROI). Seattle; 2015.
63. Bozzette SA, Ake CF, Tam HK, Phippard A, Cohen D, Scharfstein DO, et al. Long-term survival and serious cardiovascular events in HIV-infected patients treated with highly active antiretroviral therapy. JAIDS J Acquir Immune Defic Syndr. 2008;47:338–41.
64. Mills AM, Nelson M, Jayaweera D, Ruxrungtham K, Cassetti I, Girard P-M, et al. Once-daily darunavir/ritonavir vs. lopinavir/ritonavir in treatment-naive, HIV-1-infected patients: 96-week analysis. AIDS. 2009;23:1679–88.
65. Martinez E, Gonzalez-Cordon A, Ferrer E, Domingo P, Negredo E, Gutierrez F, et al. Early lipid changes with atazanavir/ritonavir or darunavir/ritonavir. HIV Med. 2014;15:330–8.
66. Ofotokun I, Na LH, Landovitz RJ, Ribaudo HJ, McComsey GA, Godfrey C, et al. Comparison of the metabolic effects of ritonavir-boosted darunavir or atazanavir versus raltegravir, and the impact of ritonavir plasma exposure: ACTG 5257. Clin Infect Dis. 2015;60:1842–51.
67. Baril J, Conway B, Giguère P, Ferko N, Hollmann S, Angel JB. A meta-analysis of the efficacy and safety of unboosted atazanavir compared with ritonavir-boosted protease inhibitor maintenance therapy in HIV-infected adults with established virological suppression after induction. HIV Med. 2013;15:301–10.
68. Elion R, Cohen C, Gathe J, Shalit P, Hawkins T, Liu HC, et al. Phase 2 study of cobicistat versus ritonavir each with once-daily atazanavir and fixed-dose emtricitabine/tenofovir df in the initial treatment of HIV infection. AIDS. 2011;25:1881–6.
69. Gallant JE, Koenig E, Andrade-Villanueva J, Chetchotisakd P, DeJesus E, Antunes F, et al. Cobicistat versus ritonavir as a pharmacoenhancer of atazanavir plus emtricitabine/tenofovir disoproxil fumarate in treatment-naive HIV type 1-infected patients: week 48 results. J Infect Dis. 2013;208:32–9.
70. Daar ES, Tierney C, Fischl MA, Sax PE, Mollan K, Budhathoki C, et al. Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1. Ann Intern Med. 2011;154:445–56.
71. Molina J-M, Clumeck N, Orkin C, Rimsky LT, Vanveggel S, Stevens M, et al. Week 96 analysis of rilpivirine or efavirenz in HIV-1-infected patients with baseline viral load ≤ 100 000 copies/mL in the pooled ECHO and THRIVE phase 3, randomized, double-blind trials. HIV Med. 2013;15:57–62.
72. Rockstroh JK, DeJesus E, Lennox JL, Yazdanpanah Y, Saag MS, Wan H, et al. Durable efficacy and safety of raltegravir versus efavirenz when combined with tenofovir/emtricitabine in treatment-naive HIV-1-infected patients: final 5-year results from STARTMRK. J Acquir Immune Defic Syndr. 2013;63:77–85.
73. Saumoy M, Sánchez-Quesada JL, Martinez E, Llibre J-M, Ribera E, Knobel H, et al. Atherosclerosis. Atherosclerosis. Elsevier Ltd; 2012;225:200–7.
74. Eron JJ, Young B, Cooper DA, Youle M, DeJesus E, Andrade Villanueva J, et al. Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials. The Lancet. Elsevier Ltd; 2010;375:396–407.
75. Raffi F, Jaeger H, Quiros-Roldan E, Albrecht H, Belonosova E, Gatell JM, et al. ArticlesOnce-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial. The Lancet Infectious Diseases. Elsevier Ltd; 2013;13:927–35.
76. Clumeck N, Molina J-M, Henry K, Gathe J, Rockstroh JK, DeJesus E, et al. A randomized, double-blind comparison of single-tablet regimen elvitegravir/cobicistat/emtricitabine/tenofovir DF vs ritonavir-boosted atazanavir plus emtricitabine/tenofovir DF for initial treatment of HIV-1 infection: analysis of week 144 results. J Acquir Immune Defic Syndr. 2014;65:e121–4.
77. Wohl DA, Cohen C, Gallant JE, Mills A, Sax PE, DeJesus E, et al. A randomized, double-blind comparison of single-tablet regimen elvitegravir/cobicistat/emtricitabine/tenofovir DF versus single-tablet regimen efavirenz/emtricitabine/tenofovir DF for initial treatment of HIV-1 infection: analysis of week 144 results. J Acquir Immune Defic Syndr. 2014;65:e118–20.
78. Sax PE, Tierney C, Collier AC, Daar ES, Mollan K, Budhathoki C, et al. Abacavir/lamivudine versus tenofovir DF/emtricitabine as part of combination regimens for initial treatment of HIV: final results. J Infect Dis. 2011;204:1191–201.
79. Behrens G, Maserati R, Rieger A, Domingo P, Abel F, Wang H, et al. Switching to tenofovir/emtricitabine from abacavir/lamivudine in HIV-infected adults with raised cholesterol: effect on lipid profiles. Antivir Ther. 2012;17:1011–20.
80. Campo R, DeJesus E, Bredeek UF, Henry K, Khanlou H, Logue K, et al. SWIFT: prospective 48-week study to evaluate efficacy and safety of switching to emtricitabine/tenofovir from lamivudine/abacavir in virologically suppressed HIV-1 infected patients on a boosted protease inhibitor containing antiretroviral regimen. Clin Infect Dis. 2013;56:1637–45.
81. Saumoy M, Ordoñez-Llanos J, Martinez E, Barragán P, Ribera E, Bonet R, et al. Low-density lipoprotein size and lipoprotein-associated phospholipase A2 in HIV-infected patients switching to abacavir or tenofovir. Antivir Ther. 2011;16:459–68.
82. Martinez E, d’Albuquerque PM, Pérez I, Pich J, Gatell JM. Abacavir/Lamivudine versus tenofovir/emtricitabine in virologically suppressed patients switching from ritonavir-boosted protease inhibitors to raltegravir. AIDS Res Hum Retrovir. 2012;:120924062217001.
83. Falcinelli E, Francisci D, Belfiori B, Petito E, Guglielmini G, Malincarne L, et al. In vivo platelet activation and platelet hyperreactivity in abacavir-treated HIV-infected patients. Thromb Haemost. 2013;110:349–57.
84. Tunjungputri RN, Van Der Ven AJ, Schonsberg A, Mathan TS, Koopmans P, Roest M, et al. Reduced platelet hyperreactivity and platelet-monocyte aggregation in HIV-infected individuals receiving a raltegravir-based regimen. AIDS. 2014;28:2091–6.
85. Hatano H, Strain MC, Scherzer R, Bacchetti P, Wentworth D, Hoh R, et al. Increase in 2-long terminal repeat circles and decrease in D-dimer after raltegravir intensification in patients with treated HIV infection: a randomized, placebo-controlled trial. J Infect Dis. 2013;208:1436–42.
86. Silva EF, Charreau I, Gourmel B, Mourah S, Kalidi I, Guillon B, et al. Decreases in inflammatory and coagulation biomarkers levels in HIV-infected patients switching from enfuvirtide to raltegravir: ANRS 138 substudy. J Infect Dis. 2013;208:892–7.
87. Trøseid M, Manner IW, Pedersen KK, Haissman JM, Kvale D, Nielsen SD. Microbial translocation and cardiometabolic risk factors in HIV infection. AIDS Res Hum Retrovir. 2014;30:514–22.
88. Hileman CO, Longenecker CT, Carman TL, McComsey GA. C-reactive protein predicts 96-week carotid intima media thickness progression in HIV-infected adults naive to antiretroviral therapy. J Acquir Immune Defic Syndr. 2014;65:340–4.
89. Kuller LH, Tracy R, Belloso W, Wit SD, Drummond F, Lane HC, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. Deeks S, editor. Plos Med. 2008;5:e203.
90. Kelesidis T, Kendall MA, Yang OO, Hodis HN, Currier JS. Biomarkers of microbial translocation and macrophage activation: association with progression of subclinical atherosclerosis in HIV-1 infection. J Infect Dis. 2012;206:1558–67.
91. McKibben RA, Margolick JB, Grinspoon S, Li X, Palella FJ, Kingsley LA, et al. Elevated levels of monocyte activation markers are associated with subclinical atherosclerosis in men with and those without hiv infection. J Infect Diss. 2014.
92. Duprez DA, Neuhaus J, Kuller LH, Tracy R, Belloso W, De Wit S, et al. Inflammation, coagulation and cardiovascular disease in HIV-infected individuals. Thorne C, editor. PLoS ONE. 2012;7:e44454.
93. Rasmussen L, Knudsen A, Katzenstein T, Gerstoft J. Soluble urokinase plasminogen activator receptor (suPAR) is a novel, independent predictive marker of myocardial infarction in HIV-1 infected patients: a nested case–control study. HIV Med. In press. 2015;:1–22.
94. Riddler SA, Smit E, Cole SR, Li R, Chmiel JS, Dobs A, et al. Impact of HIV infection and HAART on serum lipids in men. JAMA. 2003;289:2978–82.
95. Rose H, Hoy J, Woolley I, Tchoua U, Bukrinsky M, Dart A, et al. HIV infection and high density lipoprotein metabolism. Atherosclerosis. 2008;199:79–86.
96. Triant VA, Regan S, Lee H, Sax PE, Meigs JB, Grinspoon SK. Association of immunologic and virologic factors with myocardial infarction rates in a US healthcare system. JAIDS J Acquir Immune Defic Syndr. 2010;55:615–9.
97. Lichtenstein KA, Armon C, Buchacz K, Chmiel JS, Buckner K, Tedaldi EM, et al. Low CD4 + T cell count is a risk factor for cardiovascular disease events in the HIV outpatient study. Clin Infect Dis. 2010;51:435–47.
98. Lang S, Mary-Krause M, Simon A, Partisani M, Gilquin J, Cotte L, et al. HIV replication and immune status are independent predictors of the risk of myocardial infarction in HIV-infected individuals. Clin Infect Dis. 2012;55:600–7.
99. Sabin CA, Ryom L, De Wit S, Mocroft A, Phillips AN, Worm SW, et al. Associations between immune depression and cardiovascular events in HIV infection. AIDS. 2013;27:2735–48.
100. van Lelyveld SFL, Gras L, Kesselring A, Zhang S, de Wolf F, Wensing AMJ, et al. Long-term complications in patients with poor immunological recovery despite virological successful HAART in Dutch ATHENA cohort. AIDS. 2012;26:465–74.
101. Helleberg M, Kronborg G, Larsen CS, Pedersen G, Pedersen C, Obel N, et al. CD4 decline is associated with increased risk of cardiovascular disease, cancer, and death in virally suppressed patients with HIV. Clin Infect Dis. 2013;57:314–21.
102. The INSIGHT START Study Group. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015;:150720091517005.
103. D’Agostino RB. Cardiovascular risk estimation in 2012: lessons learned and applicability to the HIV population. J Infect Dis. 2012;205:S362–7.
104. Friis-Møller N, Thiébaut R, Reiss P, Weber R, Monforte AD, De Wit S, 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;17:491–501.
105. Lundgren J, Gatell JM, Furrer H, Rockstroh J, EACS Executive Committee. European AIDS Clinical Society (EACS) guidelines for the clinical management and treatment of chronic hepatitis B and C coinfection in HIV-infected adults. HIV Med. www.eacsociety.org; 2014.
106. Friis-Møller N, Worm SW. Can the risk of cardiovascular disease in HIV-infected patients be estimated from conventional risk prediction tools? Clin Infect Dis. 2007;45:1082–4.
107. Chew KW, Bhattacharya D, McGinnis KA, Horwich TB, Tseng C-H, Currier JS, et al. Coronary heart disease risk by framingham risk score in hepatitis C and HIV/Hepatitis C-coinfected persons. AIDS Res Hum Retrovir. 2015;:150511140329000.
108. Friis-Møller N, Ryom L, Smith C, Weber R, Reiss P, Dabis F, et al. An updated prediction model of the global risk of cardiovascular disease in HIV-positive persons: the Data-collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study. Eur J Prev Cardiol. 2015.
109. Salinas JL, Rentsch CT, Marconi VC, Tate J. Cumulative HIV care measures highly associated with acute myocardial infarction. Abstract 746. 22nd Conference on Retroviruses and Opportunistic Infections (CROI). Seattle; 2015.
110. Thompson-Paul A, Lichtenstein KA, Armon C. Cardiovascular disease risk prediction in the HIV Outpatient Study (HOPS). Abstract 747. 22nd Conference on Retroviruses and Opportunistic Infections (CROI). Seattle; 2015.
111. Lee FJ, Monterio P. Rosuvastatin vs. protease inhibitor switch for hypercholesterolaemia: a randomised trial - The Statin or Switch (SoS) study. Abstract 733. 22nd Conference on Retroviruses and Opportunistic Infections (CROI). Seattle; 2015.
112. Stone NJ, Robinson JG, Lichtenstein AH, Merz CNB, Blum CB, Eckel RH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults. J Am Coll Cardiol. Elsevier; 2014;63:2889–934.
113. Clement M, Park LP, Navar-Boggan AM. HIV-infected veterans and the NEW ACC/AHA cholesterol guidelines: got statins? Abstract 750. 22nd Conference on Retroviruses and Opportunistic Infections (CROI). Seattle; 2015.
114. Mosepele M, Regan S, Meigs JB. Application of new ACC/AHA cholesterol guidelines to an HIV clinical care cohort. Abstract 734. 22nd Conference on Retroviruses and Opportunistic Infections (CROI). Seattle; 2015.
115. Ray KK, Kastelein JJP, Matthijs Boekholdt S, Nicholls SJ, Khaw KT, Ballantyne CM, et al. The ACC/AHA 2013 guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults: the good the bad and the uncertain: a comparison with ESC/EAS guidelines for the management of dyslipidaemias 2011. Eur Heart J. 2014;35:960–8.
116. Chastain DB, Henderson H, Stover KR. Epidemiology and management of antiretroviral-associated cardiovascular disease. Open AIDS J. 2015;9:23–37.
117. Longenecker CT, Firstname. Rosuvastatin arrests progression of carotid Intima-media thickness in treated HIV. Abstract 137. 22nd Conference on Retroviruses and Opportunistic Infections (CROI). Seattle; 2015.
118. Lo J. Statin therapy reduces coronary noncalcified plaque volume in HIV patients: a randomized controlled trial. Abstract 136. 22nd Conference on Retroviruses and Opportunistic Infections (CROI). Seattle; 2015.