2 TEMA INNEN MATVARETRYGGHET SOM BELYSES I STUDIEN
4.4 Omorganisering
4.4.3 En ny risikokommunikasjon?
Segundo a revisão dos estudos, autores como Idiculla (2011), Vu (2013), Masiá- Canuto (2006), Brown (2005), Duro (2013), Rasmussen (2012), Mandina Ndona (2012), Kalra (2013), Petoumenos (2012), Calza (2004), Gutierrez (2012), Green (2002), Ledergerber (2007), Butt (2009), De Wit (2008), Polsky (2011), Chantry (2008), Guimarães (2007), Cahn (2010), Justman (2003), Palios (2012) e Lo (2009) associam a terapia HAART, IP e ITRN, como principal fator de risco envolvido no desenvolvimento de síndrome metabólica nos indivíduos com VIH. Os efeitos tóxicos desencadeados pela terapia HAART, que os autores verificaram são: lipodistrofia, lipoatrofia, hiperglicemia, hipertriglicemia, aumento do CT e do LDLc, diminuição do HDLc, diminuição da sensibilidade da insulina, hipoadiponectinemia e hipoleptinemia. (tabelas 14, 15, 16 e 17)
Autores como Butt (2009), Polsky (2011), Naing (2012), Brown (2010), Bertoni (2010), Arama (2013) associam a inflamação como principal fator de risco envolvido no desenvolvimento de síndrome metabólica nos indivíduos com VIH. Butt (2009), Polsky (2011) e Naing (2012) associam a inflamação derivada da coinfeção por VHC (vírus da hepatite C). Brown (2010) e Arama (2013) associam a inflamação causada pela terapia HAART e Bertoni (2010) associa a inflamação derivada da infeção VIH. Os efeitos tóxicos causados pela inflamação, que os autores verificaram são: hiperglicemia, diminuição da sensibilidade da insulina, hiperleptinemia, hipoadiponectinemia e aumento dos níveis de PCR, IL-6 e fibrinogénio, que vão contribuir para o desenvolvimento de resistência à insulina e diabetes mellitus. (tabelas 14, 15, 16 e 17)
42
Tabela 14- Revisão dos diferentes estudos: fatores de risco e efeitos tóxicos associados na síndrome metabólica.
Vários estudos/ Autores Fatores de risco associados Efeitos tóxicos (Idiculla et al., 2011) (Vu et al., 2013) (Masiá-Canuto et al., 2006) (Brown et al., 2005) (Duro et al., 2013) (Rasmussen et al., 2012)
(Mandina Ndona et al., 2012)
(Naing et al., 2012)
(Kalra e Agrawal, 2013)
(Petoumenos et al., 2012)
Tratamento HAART (IP e ITRN)
Tratamento HAART (IP)
Tratamento com IP e ITRN
Tratamento HAART (IP, ITRN, ITRNN)
Tratamento HAART (IP, ITRN)
Tratamento HAART (IP, ITRN)
Tratamento com IP e ITRN; obesidade abdominal
Co-infeção com o vírus da hepatite C
Tratamento antiretroviral com IP
Tratamento ART (ITRN e IP)
Resistência à insulina Lipodistrofia e dislipidemia Dislipidemia Diabetes mellitus, resistência à insulina, lipodistrofia e lipoatrofia. Dislipidemia Diabetes mellitus Resistência à insulina e diabetes mellitus Diabetes mellitus Resistência à insulina e diabetes mellitus Diabetes mellitus
43
Tabela 15- Revisão dos diferentes estudos: fatores de risco e efeitos tóxicos associados na síndrome metabólica.
Vários estudos/ Autores Fatores de risco associados Efeitos tóxicos (Calza et al., 2004) (Gutierrez e Balasubramanyam, 2012) (Green, 2002) (Ledergerber et al., 2007) (Butt et al., 2009)
(De Wit et al., 2008)
(Polsky et al., 2011)
Tratamento HAART (IP)
Tratamento HAART (ITRN e IP)
Tratamento HAART (IP e ITRN)
Tratamento HAART (IP e ITRN)
Co-infeção por VHC e o tratamento (IP, ITRN;
ITRNN).
Tratamento ART (ITRN, IP)
Tratamento HAART (IP) e a co-infeção por VHC
Lipodistrofia, hipertriglicemia, hipercolesterolemia, resistência à insulina e diabetes mellitus. Disglicemia Dislipidemia (elevados níveis de CT, de LDLc e TG). Diabetes mellitus Diabetes mellitus Resistência à insulina, diabetes mellitus (hiperglicemia, diminuição da sensibilidade à insulina, hipertriglicemia, aumento do CT e diminuição do HDLc) Diabetes mellitus (hiperglicemia)
44
Tabela 16- Revisão dos diferentes estudos e fatores de risco e efeitos tóxicos associados na síndrome metabólica. Vários estudos/ Autores Fatores de risco associados Efeitos tóxicos (Brown et al., 2010) (Arama et al., 2013) (Chantry et al., 2008) (Guimarães et al., 2007) (Cahn et al., 2010) (Bertoni et al., 2010) Inflamação após associação da terapia ART
Inflamação com o uso da terapia ART Tratamento HAART (IP e ITRN) Tratamento HAART (ITRN e IP) Tratamento HAART (IP) Inflamação
Resistência à insulina, diabetes mellitus.
Resistência à insulina (hiperleptinemia e hipoadiponectinemia)
Dislipidemia (aumento dos TG, do CT e redução do HDLc) e resistência à insulina. Dislipidemia (aumento de TG, CT e redução do HDLc), Disglicemia e resistência à insulina (hiperglicemia e hiperinsulinemia) e lipoatrofia. Lipoatrofia, lipodistrofia, dislipidemia, diabetes mellitus.
Diabetes (aumento dos biomarcadores inflamatórios-
45
Tabela 17- Revisão dos diferentes estudos e fatores de risco e efeitos tóxicos associados na síndrome metabólica.
Vários estudos/ Autores Fatores de risco associados
Efeitos tóxicos (Justman et al., 2003)
(Lo et al., 2009)
(Palios et al., 2012)
Tratamento com ART (IP)
HAART (IP; ITRN)
Tratamento HAART Hiperglicemia (Diabetes mellitus) Resistência à insulina, lipoatrofia, diabetes mellitus. Hipoadiponectinemia; lipodistrofia; hipoleptinemia.
46
Conclusão
A investigação científica realizada até à atualidade sobre a infeção por VIH trouxe grandes avanços, que permitiram mudar o prognóstico dos indivíduos infetados por VIH. Inicialmente os indivíduos com VIH evoluíam facilmente para o estado de SIDA e acabavam por falecer. Hoje isso já não se verifica, pois a infeção VIH assume um perfil de doença crónica. Esta razão deve-se ao facto de hoje possuirmos fármacos antiretrovirais mais eficazes, com melhor tolerabilidade e com menos efeitos adversos que fazem, por sua vez, aumentar a adesão dos indivíduos à terapêutica.
Verificou-se, contudo, que o aumento da esperança de vida dos indivíduos infetados por VIH estava, também, associada a um aumento do risco de desenvolver doença cardiovascular, diabetes, hipertensão e dislipidemia.
Os estudos realizados parecem apontar como causa dessas alterações metabólicas, a inflamação e a HAART.
Durante o processo inflamatório, causado pela infeção, há aumento plasmático de adipocinas (PCR, IL-6, TNFα, leptina). Os níveis de adipocinas como estão elevados durante o processo inflamatório, estas promovem a hiperglicemia e diminuição da sensibilidade da insulina, contribuindo de certa forma para a resistência à insulina. A presença de resistência à insulina promove a dislipidemia e, por sua vez, aumento do LDLc, triglicerídeos e diminuição do HDLc.
Em relação ao tratamento HAART, os IP exercem alguma toxicidade na mitocôndria, promovem dislipidemia (hipertriglicemia, aumento do LDLc e do CT e diminuição do HDLc), lipohipertrofia e resistência à insulina. Os ITRN exercem também toxicidade na mitocôndria, promovem a resistência à insulina, dislipidemia (hipertriglicemia, aumento do LDLc e CT e diminuição do HDLc) e lipoatrofia.
47
Bibliografia
(2001). 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, 285, pp. 2486-97.
Alberti, K. G., et al. (2009). Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation, 120, pp. 1640-5.
Alberti, K. G. e Zimmet, P. Z. (1998). Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med, 15, pp. 539-53.
Arama, V., et al. (2013). Insulin resistance and adipokines serum levels in a caucasian cohort of hiv-positive patients undergoing antiretroviral therapy: a cross sectional study.
BMC Endocrine Disorders, 13, pp. 4.
Arner, P. (1995). Differences in lipolysis between human subcutaneous and omental adipose tissues. Ann Med, 27, pp. 435-8.
Arner, P. (2005). Human fat cell lipolysis: biochemistry, regulation and clinical role.
Best Pract Res Clin Endocrinol Metab, 19, pp. 471-82.
Balkau, B. e Charles, M. A. (1999). Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med, 16, pp. 442-3.
Bertoni, A. G., et al. (2010). Inflammation and the Incidence of Type 2 Diabetes: The Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes Care, 33, pp. 804-810.
48
Bonfanti, P., et al. (2012). The feature of Metabolic Syndrome in HIV naive patients is not the same of those treated: Results from a prospective study. Biomedicine &
Pharmacotherapy, 66, pp. 348-353.
Brown, T. T., et al. (2005). Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study. Arch Intern Med, 165, pp. 1179-84.
Brown, T. T., et al. (2010). Association between systemic inflammation and incident diabetes in HIV-infected patients after initiation of antiretroviral therapy. Diabetes
Care, 33, pp. 2244-9.
Burton, A. (2003). Enfuvirtide approved for defusing HIV. Lancet Infect Dis, 3, pp. 260.
Butt, A. A., et al. (2009). HIV infection and the risk of diabetes mellitus. AIDS, 23, pp. 1227-1234 10.1097/QAD.0b013e32832bd7af.
Cahn, P., et al. (2010). Metabolic profile and cardiovascular risk factors among Latin American HIV-infected patients receiving HAART. Braz J Infect Dis, 14, pp. 158-66.
Calza, L., et al. (2004). Dyslipidaemia associated with antiretroviral therapy in HIV- infected patients. Journal of Antimicrobial Chemotherapy, 53, pp. 10-14.
Caron, M., et al. (2001). The HIV protease inhibitor indinavir impairs sterol regulatory element-binding protein-1 intranuclear localization, inhibits preadipocyte differentiation, and induces insulin resistance. Diabetes, 50, pp. 1378-88.
Chantry, C. J., et al. (2008). Lipid and Glucose Alterations in HIV-Infected Children Beginning or Changing Antiretroviral Therapy. Pediatrics, 122, pp. e129-e138.
Collier, A. C., et al. (1993). Combination therapy with zidovudine and didanosine compared with zidovudine alone in HIV-1 infection. Ann Intern Med, 119, pp. 786-93.
Dandona, P., et al. (2007). Proinflammatory effects of glucose and anti-inflammatory effect of insulin: relevance to cardiovascular disease. Am J Cardiol, 99, pp. 15b-26b.
49
Dandona, P., et al. (2009). Insulin as an anti-inflammatory and antiatherogenic modulator. J Am Coll Cardiol, 53, pp. S14-20.
Day, C. (2007). Metabolic syndrome, or What you will: definitions and epidemiology.
Diab Vasc Dis Res, 4, pp. 32-8.
De Wit, S., et al. (2008). 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, pp. 1224-9.
Deeks, S. G., et al. (2013). The end of AIDS: HIV infection as a chronic disease.
Lancet, 382, pp. 1525-33.
Drain, P. K., et al. (2007). Micronutrients in HIV-positive persons receiving highly active antiretroviral therapy. Am J Clin Nutr, 85, pp. 333-45.
Dube, M. P., et al. (2003). 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, 37, pp. 613-27.
Duro, M., et al. (2013). Lipid profile changes by high activity anti-retroviral therapy.
Clin Biochem, 46, pp. 740-4.
Eckel, R. H., et al. (2005). The metabolic syndrome. The Lancet, 365, pp. 1415-1428.
Einhorn, D., et al. (2003). American College of Endocrinology position statement on the insulin resistance syndrome. Endocr Pract, 9, pp. 237-52.
Emerman, M. e Malim, M. H. (1998). HIV-1 regulatory/accessory genes: keys to unraveling viral and host cell biology. Science, 280, pp. 1880-4.
Este, J. A., et al. (1999). Shift of clinical human immunodeficiency virus type 1 isolates from X4 to R5 and prevention of emergence of the syncytium-inducing phenotype by blockade of CXCR4. J Virol, 73, pp. 5577-85.
50
Feingold, K. R., et al. (1993). The hypertriglyceridemia of acquired immunodeficiency syndrome is associated with an increased prevalence of low density lipoprotein subclass pattern B. J Clin Endocrinol Metab, 76, pp. 1423-7.
Fischl, M. A., et al. (1987). 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, 317, pp. 185-91.
Francisco, G., et al. (2006). Serum markers of vascular inflammation in dyslipemia.
Clin Chim Acta, 369, pp. 1-16.
Freiberg, M. S., et al. (2013). HIv infection and the risk of acute myocardial infarction.
JAMA Internal Medicine, 173, pp. 614-622.
Gallo, R. C., et al. (1984). Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science, 224, pp. 500-3.
Garg, R., et al. (2003). Insulin resistance as a proinflammatory state: mechanisms, mediators, and therapeutic interventions. Curr Drug Targets, 4, pp. 487-92.
Gortmaker, S. L., et al. (2001). Effect of combination therapy including protease inhibitors on mortality among children and adolescents infected with HIV-1. N Engl J
Med, 345, pp. 1522-8.
Gottlieb, M. S., et al. (1981a). Pneumocystis Pneumonia Los Angeles [Em linha]. Disponível em <http://www.cdc.gov/mmwr/preview/mmwrhtml/june_5.htm> [Consultado em 01/09/2014].
Gottlieb, M. S., et al. (1981b). Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N Engl J Med, 305, pp. 1425-31.
Green, M. (2002). Evaluation and management of dyslipidemia in patients with HIV infection. Journal of General Internal Medicine, 17, pp. 797-810.
Grinspoon, S. e Carr, A. (2005). Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med, 352, pp. 48-62.
51
Grundy, S. M., et al. (2004). Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Arterioscler Thromb Vasc Biol, 24, pp. e13-8.
Grunfeld, C., et al. (1992). Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. J Clin Endocrinol Metab, 74, pp. 1045-52.
Guimarães, M. M. M., et al. (2007). Distribuição da gordura corporal e perfis lipídico e glicêmico de pacientes infectados pelo HIV. Arquivos Brasileiros de Endocrinologia &
Metabologia, 51, pp. 42-51.
Gupta, P., et al. (1989). Cell-to-cell transmission of human immunodeficiency virus type 1 in the presence of azidothymidine and neutralizing antibody. Journal of Virology, 63, pp. 2361-2365.
Gutierrez, A. D. e Balasubramanyam, A. (2012). Dysregulation of glucose metabolism in HIV patients: epidemiology, mechanisms, and management. Endocrine, 41, pp. 1- 10.
Hahn, B. H., et al. (2000). AIDS as a zoonosis: scientific and public health implications.
Science, 287, pp. 607-14.
Haller, H. (1977). [Epidermiology and associated risk factors of hyperlipoproteinemia].
Z Gesamte Inn Med, 32, pp. 124-8.
Hellerstein, M. K., et al. (1993). Increased de novo hepatic lipogenesis in human immunodeficiency virus infection. J Clin Endocrinol Metab, 76, pp. 559-65.
Hoffmeister, A., et al. (2001). Current Infection With Helicobacter pylori, but Not Seropositivity to Chlamydia pneumoniae or Cytomegalovirus, Is Associated With an Atherogenic, Modified Lipid Profile. Arteriosclerosis, Thrombosis, and Vascular
Biology, 21, pp. 427-432.
Hymes, K., et al. (1981). KAPOSI'S SARCOMA IN HOMOSEXUAL MEN?A REPORT OF EIGHT CASES. The Lancet, 318, pp. 598-600.
52
Idiculla, J., et al. (2011). Diabetes mellitus, insulin resistance, and metabolic syndrome in HIV-positive patients in South India. International Journal of General Medicine, 4, pp. 73-78.
Jaffe, H. W., et al. (1983). National Case-Control Study of Kaposi's Sarcoma and Pneumocystis carinii Pneumonia in Homosexual Men: Part 1, Epidemiologic Results.
Annals of Internal Medicine, 99, pp. 145-151.
Justman, J. E., et al. (2003). Protease inhibitor use and the incidence of diabetes mellitus in a large cohort of HIV-infected women. J Acquir Immune Defic Syndr, 32, pp. 298-302.
Kalra, S. e Agrawal, N. (2013). Diabetes and HIV: current understanding and future perspectives. Curr Diab Rep, 13, pp. 419-27.
Kaur, J. (2014). A Comprehensive Review on Metabolic Syndrome. Cardiology
Research and Practice, 2014, pp. 21.
Lau, C. Y., et al. (2014). Rational development of radiopharmaceuticals for HIV-1.
Nucl Med Biol, 41, pp. 299-308.
Lau, D. C., et al. (2005). Adipokines: molecular links between obesity and atheroslcerosis. Am J Physiol Heart Circ Physiol, 288, pp. H2031-41.
Ledergerber, B., et al. (2007). Factors associated with the incidence of type 2 diabetes mellitus in HIV-infected participants in the Swiss HIV Cohort Study. Clin Infect Dis, 45, pp. 111-9.
Leonard, E. G. e Mccomsey, G. A. (2005). Antiretroviral therapy in HIV-infected children: the metabolic cost of improved survival. Infect Dis Clin North Am, 19, pp. 713-29.
Lo, Y. C., et al. (2009). Risk factors for incident diabetes mellitus among HIV-infected patients receiving combination antiretroviral therapy in Taiwan: a case-control study.
53
Lyerly, H. K., et al. (1987). Human T-cell lymphotropic virus IIIB glycoprotein (gp120) bound to CD4 determinants on normal lymphocytes and expressed by infected cells serves as target for immune attack. Proc Natl Acad Sci U S A, 84, pp. 4601-5.
Mandina Ndona, M., et al. (2012). Nadir CD4+, religion, antiretroviral therapy, incidence of type 2 diabetes mellitus, and increasing rates of obesity among black Africans with HIV disease. Int J Gen Med, 5, pp. 983-90.
Masiá-Canuto, M., et al. (2006). Alteraciones lipídicas y riesgo cardiovascular asociado a la terapia antirretroviral. TITLEREVISTA, 24, pp. 637-648.
Mindel, A. e Tenant-Flowers, M. (2001). ABC of AIDS: Natural history and management of early HIV infection. Bmj, 322, pp. 1290-3.
Mohammedi, K., et al. (2011). Type B insulin resistance syndrome associated with an immune reconstitution inflammatory syndrome in an HIV-infected woman. J Clin
Endocrinol Metab, 96, pp. E653-7.
Montague, C. T., et al. (1998). Depot-related gene expression in human subcutaneous and omental adipocytes. Diabetes, 47, pp. 1384-91.
Morse, C. G. e Kovacs, J. A. (2006). Metabolic and skeletal complications of HIV infection: the price of success. Jama, 296, pp. 844-54.
Mukherjee, B., et al. (2013). Obesity and Insulin Resistance: An Abridged Molecular Correlation. Lipid Insights, 6, pp. 1-11.
Naing, C., et al. (2012). Relationship between hepatitis C virus infection and type 2 diabetes mellitus: meta-analysis. World J Gastroenterol, 18, pp. 1642-51.
Nolan, D., et al. (2008). Complications resultig from antiretroviral therapy for HIV infection. In: VOLBERDING, P., et al. (eds.) Sande´s HIV/AIDS Medicine: Medical
54
Palella, F. J., Jr., et al. (1998). Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med, 338, pp. 853-60.
Palios, J., et al. (2012). The Pathophysiology of HIV-/HAART-Related Metabolic Syndrome Leading to Cardiovascular Disorders: The Emerging Role of Adipokines.
Experimental Diabetes Research, 2012, pp. 7.
Palmisano, L. e Vella, S. (2011). A brief history of antiretroviral therapy of HIV infection: success and challenges. Ann Ist Super Sanita, 47, pp. 44-8.
Paruthi, J., et al. (2013). Adipokines in the HIV/HAART-associated lipodystrophy syndrome. Metabolism, 62, pp. 1199-205.
Pasceri, V., et al. (2000). Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation, 102, pp. 2165-8.
Perez-Matute, P., et al. (2013). Role of mitochondria in HIV infection and associated metabolic disorders: focus on nonalcoholic fatty liver disease and lipodystrophy syndrome. Oxid Med Cell Longev, 2013, pp. 493413.
Petoumenos, K., et al. (2012). Predicting the short-term risk of diabetes in HIV-positive patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. J
Int AIDS Soc, 15, pp. 17426.
Phillips, G. B. (1978). Sex hormones, risk factors and cardiovascular disease. Am J
Med, 65, pp. 7-11.
Polsky, S., et al. (2011). Incident hyperglycaemia among older adults with or at-risk for HIV infection. Antivir Ther, 16, pp. 181-8.
Rasmussen, L. D., et al. (2012). Risk of Diabetes Mellitus in Persons with and without HIV: A Danish Nationwide Population-Based Cohort Study. PLoS ONE, 7, pp. e44575.
Reaven, G. M. (1988). Banting lecture 1988. Role of insulin resistance in human disease. Diabetes, 37, pp. 1595-607.
55
Rexrode, K. M., et al. (2003). Relationship of total and abdominal adiposity with CRP and IL-6 in women. Ann Epidemiol, 13, pp. 674-82.
Ridker, P. M. (2003). Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation, 107, pp. 363-9.
Rocha, M., et al. (2014). Perspectives and potential applications of mitochondria- targeted antioxidants in cardiometabolic diseases and type 2 diabetes. Med Res Rev, 34, pp. 160-89.
Rössner, S. (2009). Eskil Kylin (1889–1975). Obesity Reviews, 10, pp. 362-362.
Ruan, H. e Lodish, H. F. (2003). Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-alpha. Cytokine Growth Factor Rev, 14, pp. 447-55.
Rutter, M. K., et al. (2004). C-reactive protein, the metabolic syndrome, and prediction of cardiovascular events in the Framingham Offspring Study. Circulation, 110, pp. 380-5.
Saag, M. S. (2012). New and investigational antiretroviral drugs for HIV infection: mechanisms of action and early research findings. Top Antivir Med, 20, pp. 162-7.
Samaras, K., et al. (2009). Proinflammatory markers, insulin sensitivity, and cardiometabolic risk factors in treated HIV infection. Obesity (Silver Spring), 17, pp. 53-9.
Santos, E., et al. (2007). Imunodeficiências. In: AROSE, F., et al. (eds.) Fundamentos
de Imunologia. Lisboa, LIDEL, pp 211-233.
Sharp, P. M., et al. (2001). The origins of acquired immune deficiency syndrome viruses: where and when? Philos Trans R Soc Lond B Biol Sci, 356, pp. 867-76.
Simmons, G., et al. (1996). Primary, syncytium-inducing human immunodeficiency virus type 1 isolates are dual-tropic and most can use either Lestr or CCR5 as coreceptors for virus entry. Journal of Virology, 70, pp. 8355-60.
Singer, P. (1977). [Diagnosis of primary hyperlipoproteinemias]. Z Gesamte Inn Med, 32, pp. 129-33 concl.
56
Soriano-Guillen, L., et al. (2008). High-sensitivity C-reactive protein is a good marker of cardiovascular risk in obese children and adolescents. Eur J Endocrinol, 159, pp. R1-4.
Swan, C. H. e Torbett, B. E. (2006). Can gene delivery close the door to HIV-1 entry after escape? J Med Primatol, 35, pp. 236-47.
Thompson, M. A., et al. (2012). Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel. Jama, 308, pp. 387-402.
Vague, J. (1956). The Degree of Masculine Differentiation of Obesities: A FACTOR DETERMINING PREDISPOSITION TO DIABETES, ATHEROSCLEROSIS, GOUT, AND URIC CALCULOUS DISEASE. The American Journal of Clinical Nutrition, 4, pp. 20-34.
Valente, A. M. M., et al. (2005). Alterações metabólicas da síndrome lipodistrófica do HIV. Arquivos Brasileiros de Endocrinologia & Metabologia, 49, pp. 871-881.
Vu, C. N., et al. (2013). Altered relationship of plasma triglycerides to HDL cholesterol in patients with HIV/HAART-associated dyslipidemia: Further evidence for a unique form of Metabolic Syndrome in HIV patients. Metabolism, 62, pp. 1014-1020.
Yudkin, J. S., et al. (2004). Low-grade inflammation may play a role in the etiology of the metabolic syndrome in patients with coronary heart disease: the HIFMECH study.
Metabolism, 53, pp. 852-7.