Abstract
Insulin resistance is associated with highly active antiretroviral therapy in HIV-infected patients, and the risk of developing insulin resistance is increased in hepatitis C virus (HCV)-infected patients. The aim of the present study was to determine whether hepatitis C virus infection constitutes an additional risk factor for insulin resistance or other prothrombotic conditions in HIV–HCV coinfected patients under highly active antiretroviral therapy. One hundred eighteen HIV-infected patients were studied: 50 who had no history of anti-HIV treatment and 68 who were receiving therapy with highly active antiretroviral treatment. The treatment-naive group consisted of 35 HCV-negative subjects and 15 HCV-positive ones. Within the treated group, 50 patients were HCV negative and 18 were HCV positive. For each patient, the lipid profile was determined and the following values measured: glucose, soluble P-selectin (as a marker of platelet activation), soluble thrombomodulin, von Willebrand factor and soluble vascular cell adhesion molecule-1 (as endothelial markers), and insulin resistance. No significant difference (p>0.05) for any variable was found among subjects with or without HCV coinfection in the treatment-naïve group. Among patients under highly active antiretroviral therapy, however, those with HCV coinfection showed higher values (p<0.05) for insulin resistance (homeostasis model assessment value: 2.65 vs. 1.79), glucose (93 vs. 86 mg/dl), endothelial markers (von Willebrand factor, 204 vs. 123%; soluble vascular cell adhesion molecule-1, 650 vs. 482 ng/ml), and platelet activation marker (soluble P-selectin, 78 vs. 51 ng/ml) in parallel with lower CD4+ cells counts (289 vs. 402 cells/mm3) and higher HIV-1 viral loads (305 vs. 50 copies/ml) compared to patients without HCV coinfection. Glucose, soluble P-selectin, and von Willebrand factor were independently related to HCV infection. The presence of HCV coinfection during HIV treatment was closely related to higher values of insulin resistance, to activated platelets, and to endothelial perturbation in parallel with lower CD4+ cell counts and higher HIV-1 viral loads compared to patients without HCV coinfection. On the basis of these results, it may be preferable to treat HCV infection prior to initiating treatment for HIV infection in HIV–HCV–coinfected patients.
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References
Grunfeld C, Tien P (2003) Difficulties in understanding the metabolic complications of acquired immune deficiency syndrome. Clin Infect Dis 37 (Suppl 2):S43–S46
Powderly WG (2002) Long-term exposure to lifelong therapies. J Acquir Immune Defic Syndr 29 (Suppl 1):S28–S40
Carr A (2003) HIV lipodystrophy: risk factors, pathogenesis, diagnosis and management. AIDS 17 (Suppl 1):s141–s148
Carr A, Samaras K, Thorisdottir A, Kaufmann G, Chishol DJ, Cooper DA (1999) Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet 353:2093–2099
Mulligan K, Grunfeld C, Tai VW, Algren H, Pang M, Chernoff DN, Lo JC, Schambelan M (2000) Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection. J Acquir Immune Defic Syndr 23:35–43
Dubé MP, Johnson DL, Currier JS, Leedom JM (1997) Protease inhibitor-associated hyperglycaemia. Lancet 350:713–714
Botella JI, Valero MA, Muñoz V, Hurtado A, Varela C (2000) Complete resolution of protease inhibitor induced diabetes mellitus. Clin Endocrinol 52:241–250
Martinez E, Conget I, Lozano L, Casamitjana R, Gatell JM (1999) Reversion of metabolic abnormalities after switching from HIV-1 protease inhibitors to nevirapine. AIDS 13:805–810
Koster JC, Remedi MS, Qiu H, Nichols CG, Hruz PW (2003) HIV protease inhibitors acutely impair glucose-stimulated insulin release. Diabetes 52:1695–1700
Grinspoon S (2003) Mechanisms and strategies for insulin resistance in acquired immune deficiency syndrome. Clin Infect Dis 37 (Suppl 2):S85–S90
Andersen O, Haugaard SB, Andersen UB, Friis-Møller N, Storgaard H, Vølund A, Nielsen JO, Iversen J, Madsbad S (2003) Lipodystrophy in human immunodeficiency virus patients impairs insulin action and induces defects in β-cell function. Metabolism 52:1343–1353
Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, Pober JS, Wick TM, Konkle BA, Schwartz BS, Barnathan ES, McCrae KR, Hug BA, Schmidt AM, Stern DM (1998) Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 91:3527–3561
Blann AD, Seigneur M, Steiner M, Miller IP, McCollum CN (1998) Circulating ICAM-1 and VCAM-1 in peripheral artery disease and hypercholesterolaemia: relationship to the location of atherosclerotic disease, smoking and in the prediction of adverse events. Thromb Haemost 79:1080–1085
Blankenberg S, Rupprecht HJ, Bickel C, Peetz D, Hafner G, Tiret L, Meyer J (2001) Circulating cell adhesion molecules and death in patients with coronary artery disease. Circulation 104:1336–1342
de Larrañaga GF, Petroni A, Deluchi G, Alonso BS, Benetucci JA (2002) Viral load and disease progression as responsible for endothelial activation and/or injury in HIV-1 infected patients. Blood Coag Fibrinol 14:15–18
Konrad T, Zeuzem S, Toffolo G, Vicini P, Teuber G, Briem D, Lormann J, Lenz T, Herrmann G, Berger A, Cobelli C, Usadel KH (2000) Severity of HCV-induced liver damage alters glucose homeostasis in noncirrhotic patients with chronic HCV infection. Digestion 62:52–59
Mehta SH, Brancati FL, Sulkowski MS, Strathdee SA, Szklo M, Thomas DL (2000) Prevalence of type 2 diabetes mellitus among persons with hepatitis C virus infection in the United States. Ann Intern Med 133:592–599
Mehta SH, Strathdee SA, Thomas DL (2001) Association between hepatitis C virus infection and diabetes mellitus. Epidemiol Rev 23:302–312
Tedaldi EM, Baker RK, Moorman AC, Alzola CF, Furhrer J, McCabe RE, Wood KC, Holmberg SD, and the HIV Outpatients Study Investigators (2003) Influence of coinfection with hepatitis C virus on morbidity and mortality due to human immunodeficiency virus infection in the era of highly active antiretroviral therapy. Clin Infect Dis 36:363–367
Klein MB, Lalonde RG, Suissa S (2003) The impact of hepatitis C virus coinfection on HIV progression before and after highly active antiretroviral therapy. J Acquir Immune Defic Syndr 33:365–372
Pérez-Cano R, Fernández-Gutiérrez C, López-Suárez A, Mira J, Girón-González JA (2002) Factors related to the chronicity and evolution of hepatitis C infection in patients co-infected by the human immunodeficiency virus. Clin Microbiol Infect 8:589–597
Sterling RK, Contos MJ, Sanyal AJ, Luketic VA, Stravitz RT, Wilson MS, Mills AS, Shiffman ML (2003) The clinical spectrum of hepatitis C virus in HIV coinfection. J Acquir Immune Defic Syndr 32:30–37
Howard AA, Klein RS, Schoenbaum EE (2003) Association of hepatitis C infection and antiretroviral use with diabetes mellitus in drugs users. Clin Infect Dis 36:1318–1323
Mehta SH, Moore RD, Thomas DL, Chaisson RE, Sulkowski MS (2003) The effect of HAART and HCV infection on the development of hyperglycemia among HIV-infected persons. J Acquir Immune Defic Syndr 33:577–584
Macias J, Pineda JA, Lozano F, Corzo JE, Ramos A, León E, García-García JA, Fernández-Rivera J, Mira JA, Gómez-Mateo J (2003) Impaired recovery of CD4+ cell counts following highly active antiretroviral therapy in drug-naive patients coinfected with human immunodeficiency virus and hepatitis C virus. Eur J Clin Microbiol Infect Dis 22:675–680
Jenny-Avital ER (2003) HCV-coinfection is associated with diabetes and CD4 decline. AIDS Clin Care 15:103
Den Brinker M, With FW, Wertheim-van Dillen PM, Jurriaans S, Weel J, van Leeuwen R, Pakker NG, Reiss P, Danner SA, Weverling GJ, Lange JM (2000) Hepatitis B and C co-infection and the risk for hepatotoxicity of highly active antiretroviral therapy in HIV-1 infection. AIDS 14:2895–2902
Uberti-Foppa C, De Bona A, Morsica G, Galli L, Gallotta G, Boeri E, Lazzarin A (2003) Pretreatment of chronic active hepatitis C in patients coinfected with HIV and hepatitis C virus reduces the hepatotoxicity associated with subsequent antiretroviral therapy. J Acquir Immune Defic Syndr 33:146–152
Shintani Y, Fujie H, Miyoshi H, Tsutsumi T, Tsukamoto K, Kimura S, Moriya K, Koike K (2004) Hepatitis C virus infection and diabetes: involvement of the virus in the development of insulin resistance. Gastroenterology 126:840–848
Duong M, Petit JM, Piroth L, Grappin M, Buisson M, Chavanet P, Hillon P, Portier H (2001) Association between insulin resistance and hepatitis C virus chronic infection in HIV-hepatitis C virus-coinfected patients undergoing antiretroviral therapy. J Acquir Immune Syndr 27:245–250
Pober JS (1988) Cytokine-mediated activation of vascular endothelium. Am J Pathol 133:426–433
Blann A, Seigneur M (1997) Soluble markers of endothelial cell function. Clin Hemorheol 17:3–11
Kaplanski G, Farnarier C, Payan MJ, Bongrand P, Durand JM (1997) Increased levels of soluble adhesion molecules in the serum of patients with hepatitis C. Dig Dis Sci 42:2277–2284
de Larrañaga G, Galich A, Puga L, Alonso B, Benetucci J (2004) Insulin resistance status is an important determinant of PAI-1 levels in HIV infected patients, independently of the lipid profile. J Thromb Haemost 2:532–534
Kim SH, Abbasi F, Reaven GM (2004) Impact of degree of obesity on surrogate estimates of insulin resistance. Diabetes Care 27:1998–2002
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This study was supported by a school grant from MSD Corporation, USA.
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de Larrañaga, G.F., Wingeyer, S.D.A.P., Puga, L.M. et al. Relationship between hepatitis C virus (HCV) and insulin resistance, endothelial perturbation, and platelet activation in HIV–HCV–coinfected patients under highly active antiretroviral treatment. Eur J Clin Microbiol Infect Dis 25, 98–103 (2006). https://doi.org/10.1007/s10096-006-0090-6
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DOI: https://doi.org/10.1007/s10096-006-0090-6