6 LO STUDIO
6.5 Conclusioni
In oltre trent’anni di gestione clinica dell’infezione da HIV, il controllo della replicazione virale e il ripristino dell’immunità negli individui affetti è più che mai un obbiettivo perseguibile, e raggiunto in oltre il 90% dei soggetti che assumono regolarmente e correttamente la terapia. La soppressione della replica virale fa sì che il numero dei linfociti CD4+ si mantenga stabile nel tempo in coloro che iniziano precocemente la terapia, e ciò evita il rischio di progressione di malattia.
L’HIV tuttavia non è eradicabile, poiché ad oggi la ricerca non è ancora riuscita a mettere a punto una strategia valida per eliminare quella quota di genoma virale che si integra nel nucleo di cellule in stato quiescente, e che può far riattivare la replicazione virale anche a distanza di molti anni nel caso in cui venga meno la pressione farmacologica.
La persistenza del virus all’interno dell’organismo porta allo sviluppo di una condizione di flogosi persistente, dovuta alle proteine virali stesse e all’attivazione del sistema immunitario. Lo stato di cronica infiammazione è, come è stato ampiamente dimostrato, una delle principali ragioni dell’invecchiamento accentuato o accelerato (cd aging) che si evidenzia in questi soggetti.
L’invecchiamento precoce porta al prematuro manifestarsi di malattie legate all’età, quali appunto le malattie cardiovascolari. Molte di queste condizioni, tra cui l’infarto del miocardio, sembrano essere più frequenti, oltre che più precoci. Appare evidente
dunque che nella gestione clinica di questi pazienti si debbano porre in atto tutte le misure necessarie a prevenire queste condizioni.
Per quanto riguarda la prevenzione delle malattie cardiovascolari, appare importante utilizzare i farmaci antiretrovirali più sicuri da un punto di vista metabolico, trattare l’ipertensione, la dislipidemia, e il diabete, ma anche e soprattutto incidere sui fattori di rischio comportamentali. Intervenire sulla riduzione dei fattori di rischio è una priorità assistenziale multidisciplinare. Incoraggiare i pazienti a smettere di fumare, ad avere un’attività fisica regolare, a seguire una dieta povera grassi animali e di zuccheri raffinati è una priorità anche e soprattutto nel soggetto infetto da HIV.
Bibliografia
1. Centers for Disease Control (CDC), “Kaposi's Sarcoma and Pneumocystis Pneumonia among Homosexual Men- New York City and California”, MMWR Morbidity and Mortality Weekly Report 30(25), 1981, 305-308.
2. Masur, H. et al, “An outbreak of community acquired Pneumocystis carinii
pneumonia: initial manifestation of cellular immune dysfunction”, The New England Journal Of Medicine, 305(24), 1981, 1431-8.
3. Barré-Sinoussi F. et al, “Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS)” Science, 220(4599), 1983, 868-87.
4. Marx J.L., “Strong new candidate for AIDS agent”, Science, 224(4648), 1984, 475- 477.
5. Marlink R, Kani P, Thior I, et al., “Reduced rate of disease development after HIV-2 infection as compared to HIV-1”, Science, 265, 1994, 1587-1590.
6. Sharp P.M., Hahn B.H., “Origins of HIV and the AIDS Pandemic”, Cold Spring Harbor Perspectives in Medicine, a006841, 2011.
7. Barré-Sinoussi F., “HIV as the cause of AIDS”, The Lancet, 348 (9019), 1996, 31-35 8. Chan D. C. et al, “Core structure of gp41 from the HIV envelope glycoprotein”, Cell,
89, 1997, 263-273.
9. Freeman M.M. et al, “Crystal structure of HIV-1 primary receptor CD4 in complex with a potent antiviral antibody”, Structure, 18 (12), 2010, 1632-1641.
10. Moroni M., Esposito R., Antinori S., “Malattie infettive”, 8° edizione, edra Masson, Milano, 2014
11. Fanales-Belasio E. et al, “HIV virology and pathogenetic mechanisms of infection: a brief overview”, ANN IST SUPER SANITÀ, 46 (1), 2010, 5-14.
12. Patel P. et al, “Estimating per-act HIV transmission risk: a systematic review”, AIDS, 28 (10), 2014, 1509-19.
13. WHO, Programmes in HIV/AIDS, Mother-to-child transmission of HIV, 2015. At <http://www.who.int/hiv/topics/mtct/about/en>
14. Dosekun O. and Fox J., “An overview of the relative risks of different sexual behaviours on
HIV transmission”, Current opinion in HIV and AIDS, 5 (4), 2010, 291-7. 15. Myron S. Cohen et al, “Antiretroviral Therapy for the Prevention of HIV-1
Transmission”, The New England Journal of Medicine, 375, 2016, 830-9.
16. CDC, Morbidity and Mortality Weekly report, Appendix A: AIDS-Defining Conditions, 2008. At https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5710a2.htm
17. Reilly, B., “Disaster and Human History: Case Studies in Nature, Society and Catastrophe”, McFarland & Co Inc, 2009
18. UNAIDS, WHO, "2007 AIDS epidemic update", 2007.
19. Wada N, Jacobson LP, Cohen M, French A, Phair J, Muñoz A., “Cause-specific life expectancies after 35 years of age for human immunodeficiency syndrome-infected and human immunodeficiency syndrome-negative individuals followed
simultaneously in long-term cohort studies, 1984-2008”, Am J Epidemiol, 177, 2013, 116–125
20. van Sighem AI, Gras LA, Reiss P, Brinkman K, de Wolf F., “Life expectancy of recently diagnosed asymptomatic HIV-infected patients approaches that of uninfected individuals.”, AIDS, 24, 2010, 1527–1535.
21. UNAIDS, WHO, “AIDS by the numbers-2016”, 2016, At
http://www.unaids.org/en/resources/documents/2016/AIDS-by-the-numbers 22. GBD 2015 HIV Collaborators, “Estimates of global, regional, and national incidence,
prevalence, and mortality of HIV, 1980–2015: the Global Burden of Disease Study 2015”, Lancet HIV, 3 (8), 2016, 361-87.
23. Notiziario dell’Istituto Superiore di Sanità, Volume 28, N.9, Supplemento 1 (2015). 24. UNAIDS. The Gap report 2014 – people aged 50 years and older; 2014.
25. Bonaventura C.T. Mpondo, “HIV Infection in the Elderly: Arising Challenges”, Journal of aging research, 2016, 2016.
26. Althoff K.N. et al, “HIV and ageing: improving quantity and quality of life”, Current Opinion in HIV & AIDS, 11 (5), 2016, 527-536.
27. AIDSinfo (1987, 20 March) 'Approval of AZT'
28. Jeffries D.J:, “Zidovudine resistant HIV”, The BMJ, 298 (6681), 1989, 1132-3. 29. Collier AC, et al. “Treatment of human immunodeficiency virus infection with
saquinavir, zidovudine, and zalcitabine.”, New England Journal of Medicine, 334, 1996, 1011–1017
30. D’Aquila RT, et al. “Nevirapine, zidovudine, and didanosine compared with zidovudine and didanosine in patients with HIV-1 infection. A randomized, double- blind, placebo-controlled trial.” National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group Protocol 241 Investigators. Ann Intern Med, 124, 1996, 1019–103.
31. Arts E.J, Hazuda D.J., “HIV-1 Antiretroviral Drug Therapy”, Cold Spring Harb Perspect Med, 2 (4), 2012.
32. Ho D.D., "Time to hit HIV, early and hard", The New England Journal of Medicine, 333 (7), 1995, 450–1
33. The INSIGHT START Study Group, "Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection", New England Journal of Medicine, 373 (9), 2015, 795–807
34. The TEMPRANO ANRS 12136 Study Group, "A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa", The New England Journal of Medicine, 373 (9), 2015, 808–822.
35. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at
http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf 36. European AIDS clinical society (EACS) Guidelines, version 8.0, October 2015.
37. Margolis A.M. et al., “A review of the toxicity of HIV medications”, J Med Toxicol, 10 (1), 2014, 26-39.
38. Shahbaz S., Manicardi M., Guaraldi G., Raggi P., “Cardiovascular disease in human immunodeficiency virus infected patients: A true or perceived risk?”, World Journal of Cardiology, 7 (10), 2015, 633-644.
39. 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, 7, 2001, 1327-1331.
40. Kotler DP., “HIV and antiretroviral therapy: lipid abnormalities and associated cardiovascular risk in HIV-infected patients.”, J Acquir Immune Defic Syndr., 49(Suppl 2), 2008, S79–S85
41. Friis-Møller N, Sabin CA, Weber R, d’Arminio Monforte A, El-Sadr WM, Reiss P, Thiébaut R, Morfeldt L, De Wit S, Pradier C, et al., “Combination antiretroviral therapy and the risk of myocardial infarction.” N Engl J Med, 349, 2003,1993–2003 42. Worm SW, Sabin C, Weber R, Reiss P, El-Sadr W, Dabis F, De Wit S, Law M,
Monforte AD, Friis-Møller N, 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., 201, 2010, 318–33.
43. UNAIDS, “HIV and aging - A special supplement to the UNAIDS report on the global AIDS epidemic 2013”, 2013. At
http://www.unaids.org/sites/default/files/media_asset/20131101_JC2563_hiv- and-aging_en_0.pdf
44. Deeks SG., “HIV infection, inflammation, immunosenescence, and aging.” Annual review of medicine, 62, 2011, 141–155.
45. Taddei, T.H., Re, V.L. & Justice, A.C., “HIV, Aging, and Viral Coinfections: Taking the Long View”, Curr HIV/AIDS Rep, 13, (2016), 269-278.
46. Hasse B, Iff M, Ledergerber B, et al., “Obesity trends and body mass index changes after starting antiretroviral treatment: the Swiss HIV Cohort Study.”, Open Forum Infect Dis, 1 (2), 2014.
47. Yuh B, Tate J, Butt AA, et al. “Weight change after antiretroviral therapy and mortality.”, Clin Infect Dis, 60, 2015, 1852–1859
48. Achhra AC, Mocroft A, Reiss P, et al. “Short-term weight gain after antiretroviral therapy initiation and subsequent risk of cardiovascular disease and diabetes: the D:A:D study.”, HIV Med, 17, 2016, 255–268.
49. Mdodo R, Frazier EL, Dube SR, Mattson CL, Sutton MY, Brooks JT, Skarbinski
J.,“Cigarette smoking prevalence among adults with HIV compared with the general adult population in the United States: cross-sectional surveys.”, Ann Intern Med., 162, 2015, 335–344.
50. Justice AC, McGinnis KA, Tate JP, et al. “Risk of mortality and physiologic injury evident with lower alcohol exposure among HIV infected compared with uninfected men.” Drug Alcohol Depend, 161, 2016, 95–103.
51. Ompad D.C. et al., “Drug use among HIV+ adults aged 50 and older: findings from the GOLD II study.”, AIDS Care, 28 (11), 2016, 1373-7.
52. Skalski L.M. et al., “Coping styles and illicit drug use in older adults with HIV/AIDS.”, Psychol Addict Behav,27(4), 2013, 1050-8.
53. Mitsuyasu R.T., “Non-AIDS-defining cancers.”, Top Antivir Med.,22(3), 2014 Jun-Jul ,660-5.
54. Naicker S., Rahmanian S., Kopp J.B., “HIV and chronic kidney disease.”, Clin Nephrol., 83(7) Suppl 1, 2015,32-8.
55. Drummond MB, Kirk GD., “HIV-associated obstructive lung diseases: insights and implications for the clinician.”, Lancet Respir Med, 2, 2014, 583–592.
56. Do AN, Rosenberg ES, Sullivan PS, et al., “Excess burden of depression among HIV- infected persons receiving medical care in the United States: data from the medical monitoring project and the behavioral risk factor surveillance system.”, PLoS One 2014; 9:e92842.
57. Fried, LP; Tangen, CM; Walston, J; Newman, AB, Hirsch, C, Gottdiener, J, Seeman, T, Tracy, R, Kop, WJ, Burke, G, McBurnie, MA, "Frailty in older adults: evidence for a
phenotype". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 56 (3), 2001, M146–56
58. Calcagno A. et al., “Ageing with HIV: a multidisciplinary review”, Infection, 43, 2015, 509–522.
59. Freiberg MS, Chang CC, Kuller LH, Skanderson M, Lowy E, Kraemer KL, Butt AA, Bidwell Goetz M, Leaf D, Oursler KA, et al., “HIV infection and the risk of acute myocardial infarction.” JAMA Intern Med., 173, 2013, 614–622.
60. Paisible AL, Chang CC, So-Armah KA, Butt AA, Leaf DA, Budoff M, Rimland D, Bedimo R, Goetz MB, Rodriguez-Barradas MC, et al., “HIV infection, cardiovascular disease risk factor profile, and risk for acute myocardial infarction.”, J Acquir Immune Defic Syndr., 68, 2015,09–216.
61. 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., 92, 2007, 2506–2512.
62. Hsue PY, Lo JC, Franklin A, Bolger AF, Martin JN, Deeks SG, Waters DD.,
“Progression of atherosclerosis as assessed by carotid intima-media thickness in patients with HIV infection.”, Circulation, 109, 2004, 1603–1608.
63. Post WS, Budoff M, Kingsley L, Palella FJ, Witt MD, Li X, George RT, Brown TT, Jacobson LP., “Associations between HIV infection and subclinical coronary atherosclerosis.”, Ann Intern Med., 160, 2014, 458–467.
64. Metkus T.S. et al., “HIV infection is associated with an increased prevalence of coronary noncalcified plaque among participants with a coronary artery calcium score of zero: Multicenter AIDS Cohort Study (MACS).”, HIV Med., 16(10), 2015 Nov, 635-9.
65. Klein DB et al., “Declining relative risk for myocardial infarction among HIV-positive compared with HIV-negative individuals with access to care.” Clin Infect Dis., 60, 2015, 1278–1280.
66. El-Sadr WM, Lundgren J, Neaton JD, Gordin F, Abrams D, Arduino RC, Babiker A, Burman W, Clumeck N, Cohen CJ, et al., “CD4+ count-guided interruption of antiretroviral treatment.”, N Engl J Med., 355, 2006, 2283–2296.
67. Silverberg MJ et al., “Immunodeficiency and risk of myocardial infarction among HIV-positive individuals with access to care.” J Acquir Immune Defic Syndr., 65, 2014, 160–166.
68. Beltràn ML et al., “Influence of immune activation and inflammatory response on cardiovascular risk associated with the human immunodeficiency virus”, Vasc Health Risk Manag., 11, 2015, 35–48.
69. Banks WA, Akerstrom V, Kastin AJ., “Adsorptive endocytosis mediates the passage of HIV-1 across the blood-brain barrier: evidence for a post-internalization
coreceptor.”, J Cell Sci., 111(Pt 4), 1998, 533–540.
70. Shieh JT, Albright AV, Sharron M, Gartner S, Strizki J, Doms RW, González-Scarano F., “Chemokine receptor utilization by human immunodeficiency virus type 1 isolates that replicate in microglia.” J Virol., 72, 1998, 4243–4249
71. Jiang J, Fu W, Wang X, Lin PH, Yao Q, Chen C., “HIV gp120 induces endothelial dysfunction in tumour necrosis factor-alpha-activated porcine and human endothelial cells.” Cardiovasc Res, 87, 2010, 366–374.
72. Dhawan S, Puri RK, Kumar A, Duplan H, Masson JM, Aggarwal BB., “Human immunodeficiency virus-1-tat protein induces the cell surface expression of endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and
intercellular adhesion molecule-1 in human endothelial cells.”, Blood., 90, 1997, 1535–1544.
73. Blankenberg S, Rupprecht HJ, Bickel C, Peetz D, Hafner G, Tiret L, Meyer J., “Circulating cell adhesion molecules and death in patients with coronary artery disease.” Circulation., 104, 2001, 1336–1342.
74. Tim Wang et al., “Increased Cardiovascular Disease Risk In The HIV-Positive Population on ART: Potential Role of HIV-Nef and Tat”, Cardiovasc Pathol. 24(5), 2015 Sep-Oct, 279–282.
75. Tim Wang et al., “Transfer of Intracellular HIV Nef to Endothelium Causes Endothelial Dysfunction”, PLoS One., 9(3), 2104, e91063.
76. Asztalos BF, Mujawar Z, Morrow MP, Grant A, Pushkarsky T, Wanke C, Shannon R, Geyer M, Kirchhoff F, Sviridov D, et al., “Circulating Nef induces dyslipidemia in simian immunodeficiency virus-infected macaques by suppressing cholesterol efflux.”, J Infect Dis., 202, 2010, 614–623.
77. Hearps AC, Maisa A, Cheng WJ, Angelovich TA, Lichtfuss GF, Palmer CS, Landay AL, Jaworowski A, Crowe SM. “HIV infection induces age-related changes to monocytes and innate immune activation in young men that persist despite combination antiretroviral therapy.”, AIDS, 26, 2012, 843–853.
78. McKibben RA et al., “Elevated levels of monocyte activation markers are associated with subclinical atherosclerosis in men with and those without HIV infection.”, J Infect Dis., 211, 2015, 1219–1228.
79. Kaplan RC, et al., “T cell activation and senescence predict subclinical carotid artery disease in HIV-infected women.” J Infect Dis., 203, 2011, 452–463.
80. Shahmanesh M et al., “The cardiovascular risk management for people living with HIV in Europe: how well are we doing?”, AIDS., 30(16), 2016 Oct 23, 2505-2518. 81. Pacek LR, Harrell PT, Martins SS, “Cigarette smoking and drug use among a
nationally representative sample of HIV-positive individuals.”, Am J Addict.,23(6), 2014 Nov-Dec, 582-90.
82. Lifson AR, Neuhaus J, Arribas JR, van den Berg-Wolf M, Labriola AM, Read TR., “Smoking-related health risks among persons with HIV in the Strategies for
Management of Antiretroviral Therapy clinical trial.” Am J Public Health., 100, 2010, 1896–1903.
83. Friis-Møller N, Weber R, Reiss P, Thiébaut R, Kirk O, d’Arminio Monforte A, Pradier C, Morfeldt L, Mateu S, Law M, et al., “Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study.” AIDS., 17, 2003, 1179–1193.
84. Helleberg M, Afzal S, Kronborg G, Larsen CS, Pedersen G, Pedersen C, Gerstoft J, Nordestgaard BG, Obel N., “Mortality attributable to smoking among HIV-1-
infected individuals: a nationwide, population-based cohort study.” Clin Infect Dis., 56, 2013, 727–734.
85. Helleberg M, May MT, Ingle SM, Dabis F, Reiss P, Fätkenheuer G, Costagliola D, d'Arminio A, Cavassini M, Smith C, Justice AC, Gill J, Sterne JA, Obel N., “Smoking and life expectancy among HIV-infected individuals on antiretroviral therapy in Europe and North America.”, AIDS.,29(2), 2015 Jan 14, 221-9.
86. Brown TT, Cole SR, Li X, Kingsley LA, Palella FJ, Riddler SA, Visscher BR, Margolick JB, Dobs AS., “Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study.” Arch Intern Med., 165, 2005, 1179– 1184.
87. De Wit S, Sabin CA, Weber R, Worm SW, Reiss P, Cazanave C, El-Sadr W, Monforte Ad, Fontas E, Law MG, 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., 31, 2008,1224–1229.
88. Tripathi A, Liese AD, Jerrell JM, Zhang J, Rizvi AA, Albrecht H, Duffus WA.,
“Incidence of diabetes mellitus in a population-based cohort of HIV-infected and non-HIV-infected persons: the impact of clinical and therapeutic factors over time.”, Diabet Med., 31(10), 2014 Oct, 1185-93.
89. Visnegarwala F, Chen L, Raghavan S, Tedaldi E., “Prevalence of diabetes mellitus and dyslipidemia among antiretroviral naive patients co-infected with hepatitis C virus (HCV) and HIV-1 compared to patients without co-infection.”, J Infect.,50(4), 2005 May, 331-7.
90. Tripathi A, Jerrell JM, Liese AD, et al., “Association of clinical and therapeutic factors with incident dyslipidemia in a cohort of human immunodeficiency virus-infected and non-infected adults: 1994–2011.”, Metab Syndr Relat Disord., 11(6), 2013, 417–426.
91. Lo J, Rosenberg ES, Fitzgerald ML, Bazner SB, Ihenachor EJ, Hawxhurst V, Borkowska AH, Wei J, Zimmerman CO, Burdo TH, et al., “High-density lipoprotein-mediated cholesterol efflux capacity is improved by treatment with antiretroviral therapy in acute human immunodeficiency virus infection.”, Open Forum Infect Dis., 2014, 1:ofu108.
92. Medina-Torne S, Ganesan A, Barahona I, Crum-Cianflone NF., “Hypertension is common among HIV-infected persons, but not associated with HAART.” J Int Assoc Physicians AIDS Care (Chic), 11, 2012, 20–25.
93. Dimala C.A. et al, “Prevalence of Hypertension in HIV/AIDS Patients on Highly Active Antiretroviral Therapy (HAART) Compared with HAART-Naïve Patients at the Limbe Regional Hospital, Cameroon.”, PLoS One., 11(2), 2016 Feb 10, :e0148100
94. De Socio G.V. et al, “Prevalence, Awareness, Treatment, and Control Rate of Hypertension in HIV-Infected Patients: The HIV-HY Study”, American Journal of Hypertension, 27(2), February 2014, 222-228.
95. D'Agostino Sr RB, Vasan RS, Pencina MJ, et al., “General cardiovascular risk profile for use in primary care: The Framingham Heart Study.” Circulation., 117(6), 2008, 743-753.
96. Preiss D, Kristensen SL., “The new pooled cohort equations risk calculator.” Can J Cardiol., 31(5), 2015, 613-619.
97. Conroy RM, Pyorala K, Fitzgerald AP, et al., “Estimation of ten-year risk of fatal cardiovascular disease in Europe: The SCORE project.”, Eur Heart J., 24, 2003, 987- 1003.
98. Friis-Moller N, Thiebaut R, Reiss P, et al., “Predicting the risk of cardiovascular disease in HIVinfected patients: The data collection on adverse effects of anti- HIV drugs study.”, Eur J Cardiovasc Prev Rehabil., 17, 2010, 491-501.
99. Petoumenos K, Reiss P, Ryom L, et al., “Increased risk of cardiovascular disease (CVD) with age in HIV-positive men: A comparison of the D:A:D CVD risk equation and general population CVD risk equations.”, HIV Med., 15(10), 2014, 595-603. 100. Thompson-Paul AM, Lichtenstein KA, Armon C., “Cardiovascular disease risk
prediction in the HIV Outpatient Study (HOPS).”, Conference on Retroviruses and Opportunistic Infections. Available from:
http://www.croiconference.org/sessions/cardiovascular-disease-risk-prediction- hiv-outpatient-study-hops.
101. Zanni MV, Fitch KV, Feldpausch M, Han A, Lee H, Lu MT, Abbara S, Ribaudo H, Douglas PS, Hoffmann U, et al., “2013 American College of Cardiology/American Heart Association and 2004 Adult Treatment Panel III cholesterol guidelines applied to HIV-infected patients with/without subclinical high-risk coronary plaque.” AIDS., 28, 2014, 2061–2070.
102. 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., 95, 2009, 1826–1835.
103. Subramanian S, Tawakol A, Burdo TH, Abbara S, Wei J, Vijayakumar J, Corsini E, Abdelbaky A, Zanni MV, Hoffmann U, et al., “Arterial inflammation in patients with HIV.”, JAMA., 308, 2012, 379–386.
104. “Cardiovascular disease mortality among HIV-infected persons”, New York City, 2001-2012 Conference on Retroviruses and Opportunistic Infections [Internet] Available from: http://www.croiconference.org/sessions/cardiovascular-disease- mortality-among-hiv-infected-persons-new-york-city-2001-2012.
105. . Regan S, Meigs JB, Massaro J, Triant V., “Evaluation of the ACC/AHA CVD risk prediction algorithm among HIV-infected patients.”, Conference on
Retroviruses and Opportunistic Infections. Available from:
http://www.croiconference.org/sessions/evaluation-accaha-cvd-risk-prediction- algorithm-among-hiv-infected-patients.
106. Available from: http: //www.croiconference.org/sessions/hiv-infected- veterans-and-new-accaha-cholesterol-guidelines-got-statins
107. De Socio G.V. et al., “Statins and Aspirin use in HIV-infected people: gap between European AIDS Clinical Society guidelines and clinical practice: the results from HIV-HY study.”, Infection., 44(5), 2016 Oct, 589-97.
108. Stein JH, Hodis H, Brown T, Ribaudo HJ, Tran TTT, Yan M, Lauer-Brodell E, McComsey G, Dube MP, Murphy RL, et al., “Prospective randomized clinical trial of the effects of three modern antiretroviral therapies on carotid intima-media thickness in HIV-infected individuals (AIDS clinical trials group study A5260S)”, J Am Coll Cardiol., 63:A1322, 2014.
109. Kelesidis T, Tran TT, Stein JH, Brown TT, Moser C, Ribaudo HJ, Dube MP, Murphy R, Yang OO, Currier JS, et al., “Changes in Inflammation and Immune Activation With Atazanavir-, Raltegravir-, Darunavir-Based Initial Antiviral Therapy: ACTG 5260s.”, Clin Infect Dis., 61, 2015, 651–660.
110. Rigshospitalet, University of Copenhagen, CHIP, Department of Infectious Diseases, available at http://www.chip.dk/TOOLS
111. 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk available at http://tools.acc.org/ASCVD-Risk-Estimator
112. Ballocca F. et al., “HIV Infection and Primary Prevention of Cardiovascular Disease: Lights and Shadows in the HAART Era”, Progress in Cardiovascular Diseases, 58, 2016, 565-576.
113. Enrica Perugini, Aldo P. Maggioni, Alessandro Boccanelli, Giuseppe Di Pasquale, “Epidemiologia delle sindromi coronariche acute in Italia”, Giornale Italiano di Cardiologia, 11 (10), 2010, 718-729.
114. Paik IJ, Kotler DP., “The prevalence and pathogenesis of diabetes mellitus in treated HIV-infection.”, Best Pract Res Clin Endocrinol Metab., 25(3), 2011 Jun, 469- 78.