Skip to main content

Advertisement

Log in

Metabolic Syndrome in HIV/HCV Co-infected Patients

  • Hepatitis C (J Raybould, Section Editor)
  • Published:
Current Treatment Options in Infectious Diseases Aims and scope Submit manuscript

Abstract

Purpose of review

We review the scope and burden of metabolic syndrome in HIV/HCV co-infected patients, risk factors, and potential mechanisms driving the increased cardio-metabolic risk in this population, and discuss relevant clinical considerations for management in the era of highly effective antiretroviral therapy (ART) and curative anti-HCV direct-acting antivirals.

Recent findings

HIV/HCV co-infected patients are at elevated risk of metabolic syndrome, attributed to (1) patient-specific factors, (2) viral-mediated effects, and (3) ART exposure. Risk factors for cardio-metabolic disorders are common in this population and include poor socioeconomic conditions, substance use, cardiovascular comorbidities, and liver/kidney disease. Chronic HIV/HCV infection induces an inflammatory and immune-activated state in the host leading to alterations in glucose and lipid metabolism. Selection of life-saving ART must carefully consider the differential metabolic risk associated with each drug class and agent, such as dyslipidemia, hyperglycemia and insulin resistance, weight gain, and hypertension. Emerging evidence supports metabolic derangements in chronic HCV may be improved by viral eradication with direct-acting antivirals; however, additional study in HIV/HCV co-infected patients is needed.

Summary

Future research programs should aim to better characterize metabolic syndrome in HIV/HCV co-infected patients with the goal of improved screening, treatment, and prevention.

Opinion statement

Persons with HIV are living longer due to highly effective antiretroviral therapy (ART). Age-related non-AIDS comorbidities (e.g., cardiovascular and metabolic disorders) increasingly account for morbidity and mortality in this population. Chronic HCV is independently associated with dyslipidemia, hepatic steatosis, and insulin resistance. The role of curative anti-HCV direct-acting antiviral (DAA) therapy in reversing metabolic derangements is being actively investigated. Less is known regarding how HIV co-infection may influence HCV-induced metabolic sequelae and potential recovery with DAAs after viral cure. However, evidence consistently supports that compared with mono-infected counterparts, patients with HIV/HCV co-infection are at increased risk of metabolic syndrome, which predisposes to the development of type 2 diabetes and cardiovascular disease. This is likely multifactorial due to patient-specific factors, direct effects of chronic HIV/HCV infection on glucose and lipid metabolism, and cardio-metabolic toxicities associated with long-term ART use. Newer antiretrovirals, particularly integrase strand transfer inhibitors and tenofovir alafenamide, have been associated with weight gain and dyslipidemia, respectively. Additional investigation of the mechanisms—both viral- and ART-mediated—driving metabolic syndrome in HIV/HCV co-infection is needed; in addition to the potential for metabolic reversal following DAA therapy. Finally, further studies evaluating appropriate screening modalities and intervals, prevention tools, and therapeutics are needed to inform the clinical management of metabolic syndrome in patients with HIV/HCV co-infection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Marcus JL, Chao CR, Leyden WA, et al. Narrowing the gap in life expectancy between HIV-infected and HIV-uninfected individuals with access to care. J Acquir Immune Defic Syndr. 2016;73(1):39–46. https://doi.org/10.1097/QAI.0000000000001014.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Centers for Disease Control and Prevention. HIV surveillance report, 2017; vol. 29. http://www.cdc.gov/hiv/library/reports/hiv-surveillance.html. Published November 2018. Accessed [June 1, 2019].

  3. Gallant J, Hsue PY, Shreay S, Meyer N. Comorbidities among US patients with prevalent HIV infection–a trend analysis. J Infect Dis. 2017;216(12):1525–33. https://doi.org/10.1093/infdis/jix518.

    Article  PubMed  Google Scholar 

  4. Neuhaus J, Angus B, Kowalska JD, et al. Risk of all-cause mortality associated with nonfatal AIDS and serious non-AIDS events among adults infected with HIV. AIDS. 2010;24(5):697–706. https://doi.org/10.1097/QAD.0b013e3283365356.

    Article  PubMed  Google Scholar 

  5. Antiretroviral therapy cohort collaboration. Causes of death in HIV-1-infected patients treated with antiretroviral therapy, 1996-2006: collaborative analysis of 13 HIV cohort studies. Clin Infect Dis. 2010;50(10):1387–96. https://doi.org/10.1086/652283.

    Article  Google Scholar 

  6. Schouten J, Wit FW, Stolte IG, et al. Cross-sectional comparison of the prevalence of age-associated comorbidities and their risk factors between HIV-infected and uninfected individuals: the AGEhIV cohort study. Clin Infect Dis. 2014;59(12):1787–97. https://doi.org/10.1093/cid/ciu701.

    Article  CAS  PubMed  Google Scholar 

  7. Cole MB, Galárraga O, Rahman M, Wilson IB. Trends in comorbid conditions among medicaid enrollees with HIV. Open Forum Infect Dis. 2019;6(4):ofz124. https://doi.org/10.1093/ofid/ofz124.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Staples CT, Rimland D, Dudas D. Hepatitis C in the HIV (human immunodeficiency virus) Atlanta V.A. (Veterans Affairs Medical Center) Cohort Study (HAVACS): the effect of coinfection on survival. Clin Infect Dis. 1999;29(1):150–4. https://doi.org/10.1086/520144.

    Article  PubMed  Google Scholar 

  9. Benhamou Y, Bochet M, Di Martino V, et al. Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. Multivirc Group Hepatol. 1999;30(4):1054–8. https://doi.org/10.1002/hep.510300409.

    Article  CAS  Google Scholar 

  10. Kirk GD, Mehta SH, Astemborski J, et al. HIV, age, and the severity of hepatitis C virus-related liver disease: a cohort study. Ann Intern Med. 2013;158(9):658–66. https://doi.org/10.7326/0003-4819-158-9-201305070-00604.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Fierer DS, Dieterich DT, Fiel MI, et al. Rapid progression to decompensated cirrhosis, liver transplant, and death in HIV-infected men after primary hepatitis C virus infection. Clin Infect Dis. 2013;56(7):1038–43. https://doi.org/10.1093/cid/cis1206.

    Article  PubMed  Google Scholar 

  12. Graham CS, Baden LR, Yu E, et al. Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis. Clin Infect Dis. 2001;33(4):562–9. https://doi.org/10.1086/321909.

    Article  CAS  PubMed  Google Scholar 

  13. Bedimo R, Abodunde O. Metabolic and cardiovascular complications in HIV/HCV-co-infected patients. Curr HIV/AIDS Rep. 2016;13(6):328–39. https://doi.org/10.1007/s11904-016-0333-9.

    Article  PubMed  Google Scholar 

  14. Slama L, Le Camus C, Serfaty L, Pialoux G, Capeau J, Gharakhanian S. Metabolic disorders and chronic viral disease: the case of HIV and HCV. Diabetes Metab. 2009;35(1):1–11. https://doi.org/10.1016/j.diabet.2008.08.003.

    Article  CAS  PubMed  Google Scholar 

  15. Freiberg MS, Chang C-CH, Skanderson M, et al. The risk of incident coronary heart disease among veterans with and without HIV and hepatitis C. Circ Cardiovasc Qual Outcomes. 2011;4(4):425–32. https://doi.org/10.1161/CIRCOUTCOMES.110.957415.

    Article  PubMed  PubMed Central  Google Scholar 

  16. McKibben RA, Haberlen SA, Post WS, et al. A cross-sectional study of the association between chronic hepatitis C virus infection and subclinical coronary atherosclerosis among participants in the multicenter AIDS cohort study. J Infect Dis. 2016;213(2):257–65. https://doi.org/10.1093/infdis/jiv396.

    Article  PubMed  Google Scholar 

  17. Shiffman ML, Gunn NT. Impact of hepatitis C virus therapy on metabolism and public health. Liver Int. 2017;37(Suppl 1):13–8. https://doi.org/10.1111/liv.13282.

    Article  PubMed  Google Scholar 

  18. Banks DE, Bogler Y, Bhuket T, Liu B, Wong RJ. Significant disparities in risks of diabetes mellitus and metabolic syndrome among chronic hepatitis C virus patients in the U.S. Diabetes Metab Syndr. 2017;11(Suppl 1):S153–8. https://doi.org/10.1016/j.dsx.2016.12.025.

    Article  PubMed  Google Scholar 

  19. Marks K, Naggie S. Management of Hepatitis C in 2019. JAMA. 2019. https://doi.org/10.1001/jama.2019.5353.

    Article  PubMed  Google Scholar 

  20. Collins LF, Chan A, Zheng J, et al. Direct-acting antivirals improve access to care and cure for patients with HIV and chronic HCV infection. Open Forum Infect Dis. 2018;5(1):ofx264. https://doi.org/10.1093/ofid/ofx264.

    Article  PubMed  Google Scholar 

  21. Lanini S, Scognamiglio P, Pisapia R, Minosse C, Agresta A, Ippolito G. Recovery of metabolic impairment in patients who cleared chronic hepatitis C infection after direct-acting antiviral therapy. Int J Antimicrob Agents. 2019;53(5):559–63. https://doi.org/10.1016/j.ijantimicag.2018.11.024.

    Article  CAS  PubMed  Google Scholar 

  22. Alberti KGMM, Eckel RH, Grundy SM, et al. 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. 2009;120(16):1640–5. https://doi.org/10.1161/CIRCULATIONAHA.109.192644.

    Article  CAS  PubMed  Google Scholar 

  23. Sobieszczyk ME, Hoover DR, Anastos K, et al. Prevalence and predictors of metabolic syndrome among HIV-infected and HIV-uninfected women in the Women’s Interagency HIV Study. J Acquir Immune Defic Syndr. 2008;48(3):272–80. https://doi.org/10.1097/QAI.0b013e31817af461.

    Article  CAS  PubMed  Google Scholar 

  24. Worm SW, Friis-Møller N, Bruyand M, et al. High prevalence of the metabolic syndrome in HIV-infected patients: impact of different definitions of the metabolic syndrome. AIDS. 2010;24(3):427–35. https://doi.org/10.1097/QAD.0b013e328334344e.

    Article  PubMed  Google Scholar 

  25. Colaci M, Malatino L, Antonelli A, Fallahi P, Giuggioli D, Ferri C. Endocrine disorders associated with hepatitis C virus chronic infection. Rev Endocr Metab Disord. 2018;19(4):397–403. https://doi.org/10.1007/s11154-018-9475-y.

    Article  CAS  PubMed  Google Scholar 

  26. Wand H, Calmy A, Carey DL, et al. Metabolic syndrome, cardiovascular disease and type 2 diabetes mellitus after initiation of antiretroviral therapy in HIV infection. AIDS. 2007;21(18):2445–53. https://doi.org/10.1097/QAD.0b013e3282efad32.

    Article  CAS  PubMed  Google Scholar 

  27. Fabiani S, Fallahi P, Ferrari SM, Miccoli M, Antonelli A. Hepatitis C virus infection and development of type 2 diabetes mellitus: Systematic review and meta-analysis of the literature. Rev Endocr Metab Disord. 2018;19(4):405–20. https://doi.org/10.1007/s11154-017-9440-1.

    Article  PubMed  Google Scholar 

  28. Moucari R, Asselah T, Cazals-Hatem D, et al. Insulin resistance in chronic hepatitis C: association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis. Gastroenterology. 2008;134(2):416–23. https://doi.org/10.1053/j.gastro.2007.11.010.

    Article  CAS  PubMed  Google Scholar 

  29. Li X, Gao Y, Xu H, Hou J, Gao P. Diabetes mellitus is a significant risk factor for the development of liver cirrhosis in chronic hepatitis C patients. Sci Rep. 2017;7(1):9087. https://doi.org/10.1038/s41598-017-09825-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Marceau P, Biron S, Hould FS, et al. Liver pathology and the metabolic syndrome X in severe obesity. J Clin Endocrinol Metab. 1999;84(5):1513–7. https://doi.org/10.1210/jcem.84.5.5661.

    Article  CAS  PubMed  Google Scholar 

  31. Butt AA, Yan P, Chew KW, et al. Risk of Acute Myocardial Infarction Among Hepatitis C Virus (HCV)-Positive and HCV-Negative Men at Various Lipid Levels: Results From ERCHIVES. Clin Infect Dis. 2017;65(4):557–65. https://doi.org/10.1093/cid/cix359.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Petta S, Maida M, Macaluso FS, et al. Hepatitis C virus infection is associated with increased cardiovascular mortality: a meta-analysis of observational studies. Gastroenterology. 2016;150(1):145–155.e4; quiz e15-16. https://doi.org/10.1053/j.gastro.2015.09.007.

    Article  PubMed  Google Scholar 

  33. Leone S, Lorenzini P, Cozzi-Lepri A, et al. Impact of diabetes on the risk of serious liver events and liver-related deaths in people living with HIV and hepatitis C co-infection: data from the ICONA Foundation Cohort Study. Eur J Clin Microbiol Infect Dis. 2019. https://doi.org/10.1007/s10096-019-03618-8.

    Article  Google Scholar 

  34. Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study Group, Weber R, Sabin C, et al. HBV or HCV coinfections and risk of myocardial infarction in HIV-infected individuals: the D:A:D Cohort Study. Antivir Ther (Lond). 2010;15(8):1077–86. https://doi.org/10.3851/IMP1681.

    Article  Google Scholar 

  35. Bedimo R, Westfall AO, Mugavero M, Drechsler H, Khanna N, Saag M. Hepatitis C virus coinfection and the risk of cardiovascular disease among HIV-infected patients. HIV Med. 2010;11(7):462–8. https://doi.org/10.1111/j.1468-1293.2009.00815.x.

    Article  CAS  PubMed  Google Scholar 

  36. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002;287(3):356–9. https://doi.org/10.1001/jama.287.3.356.

    Article  PubMed  Google Scholar 

  37. Moore JX, Chaudhary N, Akinyemiju T. Metabolic syndrome prevalence by race/ethnicity and sex in the United States, national health and nutrition examination survey, 1988–2012. Prev Chronic Dis. 2017;14. https://doi.org/10.5888/pcd14.160287.

  38. Park Y-W, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB. The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988-1994. Arch Intern Med. 2003;163(4):427–36.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Hanley AJG, Williams K, Festa A, Wagenknecht LE, D’Agostino RB, Haffner SM. Liver markers and development of the metabolic syndrome: the insulin resistance atherosclerosis study. Diabetes. 2005;54(11):3140–7. https://doi.org/10.2337/diabetes.54.11.3140.

    Article  CAS  PubMed  Google Scholar 

  40. Chen J, Muntner P, Hamm LL, et al. The metabolic syndrome and chronic kidney disease in U.S. adults. Ann Intern Med. 2004;140(3):167–74. https://doi.org/10.7326/0003-4819-140-3-200402030-00007.

    Article  PubMed  Google Scholar 

  41. Mdodo R, Frazier EL, Dube SR, et al. Cigarette smoking prevalence among adults with HIV compared with the general adult population in the United States: cross-sectional surveys. Ann Intern Med. 2015;162(5):335–44. https://doi.org/10.7326/M14-0954.

    Article  PubMed  Google Scholar 

  42. Lai H, Moore R, Celentano DD, et al. HIV Infection Itself May Not Be Associated With Subclinical Coronary Artery Disease Among African Americans Without Cardiovascular Symptoms. J Am Heart Assoc. 2016;5(3):e002529. https://doi.org/10.1161/JAHA.115.002529.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Lorenz DR, Dutta A, Mukerji SS, Holman A, Uno H, Gabuzda D. Marijuana use impacts midlife cardiovascular events in HIV-infected men. Clin Infect Dis. 2017;65(4):626–35. https://doi.org/10.1093/cid/cix391.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Helleberg M, Afzal S, Kronborg G, et al. Mortality attributable to smoking among HIV-1-infected individuals: a nationwide, population-based cohort study. Clin Infect Dis. 2013;56(5):727–34. https://doi.org/10.1093/cid/cis933.

    Article  PubMed  Google Scholar 

  45. Younossi ZM, Stepanova M, Nader F, Younossi Z, Elsheikh E. Associations of chronic hepatitis C with metabolic and cardiac outcomes. Aliment Pharmacol Ther. 2013;37(6):647–52. https://doi.org/10.1111/apt.12234.

    Article  CAS  PubMed  Google Scholar 

  46. Rafiq N, Stepanova M, Lam B, Nader F, Srishord M, Younossi ZM. Predictors of chronic liver disease in individuals with human immunodeficiency virus infection. Ann Hepatol. 2013;13(1):60–4.

    Article  PubMed  Google Scholar 

  47. Kupin WL. Viral-associated GN: hepatitis C and HIV. Clin J Am Soc Nephrol. 2017;12(8):1337–42. https://doi.org/10.2215/CJN.04320416.

    Article  CAS  PubMed  Google Scholar 

  48. Kalayjian RC, Lau B, Mechekano RN, et al. Risk factors for chronic kidney disease in a large cohort of HIV-1 infected individuals initiating antiretroviral therapy in routine care. AIDS. 2012;26(15):1907–15. https://doi.org/10.1097/QAD.0b013e328357f5ed.

    Article  CAS  PubMed  Google Scholar 

  49. Fischer MJ, Wyatt CM, Gordon K, et al. Hepatitis C and the risk of kidney disease and mortality in veterans with HIV. J Acquir Immune Defic Syndr. 2010;53(2):222–6. https://doi.org/10.1097/QAI.0b013e3181b980d4.

    Article  PubMed  PubMed Central  Google Scholar 

  50. 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(8):1074–81. https://doi.org/10.1086/521935.

    Article  PubMed  Google Scholar 

  51. Savès M, Chêne G, Ducimetière P, et al. Risk factors for coronary heart disease in patients treated for human immunodeficiency virus infection compared with the general population. Clin Infect Dis. 2003;37(2):292–8. https://doi.org/10.1086/375844.

    Article  PubMed  Google Scholar 

  52. Grunfeld C, Pang M, Doerrler W, Shigenaga JK, Jensen P, Feingold KR. Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. J Clin Endocrinol Metab. 1992;74(5):1045–52. https://doi.org/10.1210/jcem.74.5.1373735.

    Article  CAS  PubMed  Google Scholar 

  53. Riddler SA, Smit E, Cole SR, et al. Impact of HIV infection and HAART on serum lipids in men. JAMA. 2003;289(22):2978–82. https://doi.org/10.1001/jama.289.22.2978.

    Article  CAS  PubMed  Google Scholar 

  54. Butt AA, Yan P, Simon TG, Chung RT, Abou-Samra A-B, ERCHIVES study team. Changes in circulating lipids level over time after acquiring HCV infection: results from ERCHIVES. BMC Infect Dis. 2015;15:510. https://doi.org/10.1186/s12879-015-1268-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Cooper CL, Mills E, Angel JB. Mitigation of antiretroviral-induced hyperlipidemia by hepatitis C virus co-infection. AIDS. 2007;21(1):71–6. https://doi.org/10.1097/QAD.0b013e3280110ada.

    Article  PubMed  Google Scholar 

  56. Patroni A, Torti C, Tomasoni L, et al. Effect of highly active antiretroviral therapy (HAART) and hepatitis C Co-infection on hyperlipidemia in HIV-infected patients: a retrospective longitudinal study. HIV Clin Trials. 2002;3(6):451–61. https://doi.org/10.1310/hct.2002.3.6.002.

    Article  PubMed  Google Scholar 

  57. Seaberg EC, Muñoz A, Lu M, et al. Association between highly active antiretroviral therapy and hypertension in a large cohort of men followed from 1984 to 2003. AIDS. 2005;19(9):953–60. https://doi.org/10.1097/01.aids.0000171410.76607.f8.

    Article  PubMed  Google Scholar 

  58. van Zoest RA, Wit FW, Kooij KW, et al. Higher prevalence of hypertension in HIV-1-infected patients on combination antiretroviral therapy is associated with changes in body composition and prior Stavudine exposure. Clin Infect Dis. 2016;63(2):205–13. https://doi.org/10.1093/cid/ciw285.

    Article  CAS  PubMed  Google Scholar 

  59. Gelpi M, Afzal S, Lundgren J, et al. Higher risk of abdominal obesity, elevated low-density lipoprotein cholesterol, and hypertriglyceridemia, but not of hypertension, in people living with human immunodeficiency virus (HIV): results from the Copenhagen comorbidity in HIV infection study. Clin Infect Dis. 2018;67(4):579–86. https://doi.org/10.1093/cid/ciy146.

    Article  CAS  PubMed  Google Scholar 

  60. Herrin M, Tate JP, Akgün KM, et al. Weight gain and incident diabetes among HIV-infected veterans initiating antiretroviral therapy compared with uninfected individuals. J Acquir Immune Defic Syndr. 2016;73(2):228–36. https://doi.org/10.1097/QAI.0000000000001071.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Currier JS, Taylor A, Boyd F, et al. Coronary heart disease in HIV-infected individuals. J Acquir Immune Defic Syndr. 2003;33(4):506–12.

    Article  PubMed  Google Scholar 

  62. Obel N, Thomsen HF, Kronborg G, et al. Ischemic heart disease in HIV-infected and HIV-uninfected individuals: a population-based cohort study. Clin Infect Dis. 2007;44(12):1625–31. https://doi.org/10.1086/518285.

    Article  PubMed  Google Scholar 

  63. Drozd DR, Kitahata MM, Althoff KN, et al. Increased risk of myocardial infarction in HIV-infected individuals in North America Compared With the General Population. J Acquir Immune Defic Syndr. 2017;75(5):568–76. https://doi.org/10.1097/QAI.0000000000001450.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Friis-Møller N, Sabin CA, Weber R, et al. Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med. 2003;349(21):1993–2003. https://doi.org/10.1056/NEJMoa030218.

    Article  PubMed  Google Scholar 

  65. Piconi S, Parisotto S, Rizzardini G, et al. Atherosclerosis is associated with multiple pathogenic mechanisms in HIV-infected antiretroviral-naive or treated individuals. AIDS. 2013;27(3):381–9. https://doi.org/10.1097/QAD.0b013e32835abcc9.

    Article  PubMed  Google Scholar 

  66. Mallon PW, Miller J, Cooper DA, Carr A. Prospective evaluation of the effects of antiretroviral therapy on body composition in HIV-1-infected men starting therapy. AIDS. 2003;17(7):971–9. https://doi.org/10.1097/01.aids.0000060348.78202.74.

    Article  CAS  PubMed  Google Scholar 

  67. Heath KV, Hogg RS, Chan KJ, et al. Lipodystrophy-associated morphological, cholesterol and triglyceride abnormalities in a population-based HIV/AIDS treatment database. AIDS. 2001;15(2):231–9.

    Article  CAS  PubMed  Google Scholar 

  68. Shlay JC, Sharma S, Peng G, Gibert CL, Grunfeld C. Long-term subcutaneous tissue changes among antiretroviral-naive persons initiating stavudine, zidovudine, or abacavir with lamivudine. J Acquir Immune Defic Syndr. 2008;48(1):53–62.

    Article  CAS  PubMed  Google Scholar 

  69. Jacobson DL, Knox T, Spiegelman D, Skinner S, Gorbach S, Wanke C. Prevalence of, evolution of, and risk factors for fat atrophy and fat deposition in a cohort of HIV-infected men and women. Clin Infect Dis. 2005;40(12):1837–45. https://doi.org/10.1086/430379.

    Article  PubMed  Google Scholar 

  70. Addy CL, Gavrila A, Tsiodras S, Brodovicz K, Karchmer AW, Mantzoros CS. Hypoadiponectinemia is associated with insulin resistance, hypertriglyceridemia, and fat redistribution in human immunodeficiency virus-infected patients treated with highly active antiretroviral therapy. J Clin Endocrinol Metab. 2003;88(2):627–36. https://doi.org/10.1210/jc.2002-020795.

    Article  CAS  PubMed  Google Scholar 

  71. Duong M, Petit JM, Piroth L, et al. Association between insulin resistance and hepatitis C virus chronic infection in HIV-hepatitis C virus-coinfected patients undergoing antiretroviral therapy. J Acquir Immune Defic Syndr. 2001;27(3):245–50.

    Article  CAS  PubMed  Google Scholar 

  72. Parrinello CM, Landay AL, Hodis HN, et al. Treatment-related changes in serum lipids and inflammation: clinical relevance remains unclear. Analyses from the Women’s Interagency HIV study. AIDS. 2013;27(9):1516–9. https://doi.org/10.1097/QAD.0b013e32835fd8a9.

    Article  CAS  PubMed  Google Scholar 

  73. Lapadula G, Torti C, Paraninfo G, et al. Influence of hepatitis C genotypes on lipid levels in HIV-positive patients during highly active antiretroviral therapy. Antivir Ther (Lond). 2006;11(4):521–7.

    CAS  Google Scholar 

  74. 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(10):1179–84. https://doi.org/10.1001/archinte.165.10.1179.

    Article  PubMed  Google Scholar 

  75. De Wit S, Sabin CA, Weber R, 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(6):1224–9. https://doi.org/10.2337/dc07-2013.

    Article  PubMed  Google Scholar 

  76. DAD Study Group, Friis-Møller N, Reiss P, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med. 2007;356(17):1723–35. https://doi.org/10.1056/NEJMoa062744.

    Article  Google Scholar 

  77. • Arribas JR, Thompson M, Sax PE, et al. Brief report: randomized, double-blind comparison of Tenofovir alafenamide (TAF) vs Tenofovir disoproxil fumarate (TDF), each coformulated with Elvitegravir, Cobicistat, and Emtricitabine (E/C/F) for initial HIV-1 treatment: week 144 results. J Acquir Immune Defic Syndr. 2017;75(2):211–8. https://doi.org/10.1097/QAI.0000000000001350Results at 144 weeks of two double-blind phase three trials demonstrated superiority of tenofovir alafenamide- versus tenofovir disoproxil fumarate-backed initial HIV therapy with improved renal and bone safety indices in the tenofovir alafenamide group, however, increased lipid profiles.

    Article  CAS  PubMed  Google Scholar 

  78. Gallant JE, Daar ES, Raffi F, et al. Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate given as fixed-dose combinations containing emtricitabine as backbones for treatment of HIV-1 infection in virologically suppressed adults: a randomised, double-blind, active-controlled phase 3 trial. Lancet HIV. 2016;3(4):e158–65. https://doi.org/10.1016/S2352-3018(16)00024-2.

    Article  PubMed  Google Scholar 

  79. Gupta SK, Post FA, Arribas JR, et al. Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate: a pooled analysis of 26 clinical trials. AIDS. 2019;33(9):1455–65. https://doi.org/10.1097/QAD.0000000000002223.

    Article  CAS  PubMed  Google Scholar 

  80. Young J, Xiao Y, Moodie EEM, et al. Effect of cumulating exposure to Abacavir on the risk of cardiovascular disease events in patients from the Swiss HIV cohort study. J Acquir Immune Defic Syndr. 2015;69(4):413–21. https://doi.org/10.1097/QAI.0000000000000662.

    Article  CAS  PubMed  Google Scholar 

  81. Worm SW, Sabin C, Weber R, 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(3):318–30. https://doi.org/10.1086/649897.

    Article  CAS  PubMed  Google Scholar 

  82. Ding X, Andraca-Carrera E, Cooper C, et al. No association of abacavir use with myocardial infarction: findings of an FDA meta-analysis. J Acquir Immune Defic Syndr. 2012;61(4):441–7. https://doi.org/10.1097/QAI.0b013e31826f993c.

    Article  CAS  PubMed  Google Scholar 

  83. Milinkovic, Ana, Berger, Florian, Arenas-Pinto, Alejandro, Mauss, Stefan. Lipid changes associated with TAF are reversible by switching back to TDF. Presented at the: Conference on Retroviruses and Opportunistic Infections 2019; 2019; Seattle, WA.

  84. Ofotokun I, Na LH, Landovitz RJ, 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(12):1842–51. https://doi.org/10.1093/cid/civ193.

    Article  PubMed  PubMed Central  Google Scholar 

  85. LaFleur J, Bress AP, Rosenblatt L, et al. Cardiovascular outcomes among HIV-infected veterans receiving atazanavir. AIDS. 2017;31(15):2095–106. https://doi.org/10.1097/QAD.0000000000001594.

    Article  CAS  PubMed  Google Scholar 

  86. Ryom L, Lundgren JD, El-Sadr W, et al. Cardiovascular disease and use of contemporary protease inhibitors: the D:A:D international prospective multicohort study. Lancet HIV. 2018;5(6):e291–300. https://doi.org/10.1016/S2352-3018(18)30043-2.

    Article  PubMed  Google Scholar 

  87. Muccini C, Galli L, Poli A, et al. Brief report: hyperbilirubinemia is associated with a decreased risk of carotid atherosclerosis in HIV-infected patients on virological suppression. J Acquir Immune Defic Syndr. 2018;79(5):617–23. https://doi.org/10.1097/QAI.0000000000001854.

    Article  CAS  PubMed  Google Scholar 

  88. Crane HM, Nance RM, Heckbert SR, et al. Association between Bilirubin, Atazanavir, and cardiovascular disease events among people living with HIV across the United States. J Acquir Immune Defic Syndr. 2019;81(5):e141–7. https://doi.org/10.1097/QAI.0000000000002071.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Fontas E, van Leth F, Sabin CA, et al. Lipid profiles in HIV-infected patients receiving combination antiretroviral therapy: are different antiretroviral drugs associated with different lipid profiles? J Infect Dis. 2004;189(6):1056–74. https://doi.org/10.1086/381783.

    Article  CAS  PubMed  Google Scholar 

  90. Tebas P, Sension M, Arribas J, et al. Lipid levels and changes in body fat distribution in treatment-naive, HIV-1-Infected adults treated with rilpivirine or Efavirenz for 96 weeks in the ECHO and THRIVE trials. Clin Infect Dis. 2014;59(3):425–34. https://doi.org/10.1093/cid/ciu234.

    Article  CAS  PubMed  Google Scholar 

  91. Thompson M, Orkin C, Molina J-M, et al. Once-daily doravirine for initial treatment of adults living with HIV-1: an integrated safety analysis. Clin Infect Dis. 2019. https://doi.org/10.1093/cid/ciz423.

  92. •• Venter WDF, Moorhouse M, Sokhela S, et al. Dolutegravir plus two different prodrugs of Tenofovir to treat HIV. N Engl J Med. 2019. https://doi.org/10.1056/NEJMoa1902824This 96-week, phase three, open-label, randomized trial in South Africa comparing dolutegravir (with emtricitabine plus tenofovir alafenamide or tenofovir disoproxil fumarate) with efavirenz-based antiretroviral therapy showed significant weight gain in the dolutegravir group, especially when combined with tenofovir alafenamide and in female patients.

    Article  CAS  PubMed  Google Scholar 

  93. NAMSAL ANRS 12313 Study Group. Dolutegravir-based or low-dose Efavirenz-based regimen for the treatment of HIV-1. N Engl J Med. 2019. https://doi.org/10.1056/NEJMoa1904340.

  94. Kerchberger AM, Sheth AN, Angert CD, et al. Integrase strand transfer inhibitors are associated with weight gain in women. Presented at the: Conference on Retroviruses and Opportunistic Infections 2019; 2019; Seattle, WA.

  95. Gaslightwala I, Bini EJ. Impact of human immunodeficiency virus infection on the prevalence and severity of steatosis in patients with chronic hepatitis C virus infection. J Hepatol. 2006;44(6):1026–32. https://doi.org/10.1016/j.jhep.2006.02.009.

    Article  CAS  PubMed  Google Scholar 

  96. Schaefer EAK, Chung RT. HCV and host lipids: an intimate connection. Semin Liver Dis. 2013;33(4):358–68. https://doi.org/10.1055/s-0033-1358524.

    Article  CAS  PubMed  Google Scholar 

  97. Morse CG, McLaughlin M, Matthews L, et al. Nonalcoholic steatohepatitis and hepatic fibrosis in HIV-1-monoinfected adults with elevated aminotransferase levels on antiretroviral therapy. Clin Infect Dis. 2015;60(10):1569–78. https://doi.org/10.1093/cid/civ101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Bräu N, Salvatore M, Ríos-Bedoya CF, et al. Slower fibrosis progression in HIV/HCV-coinfected patients with successful HIV suppression using antiretroviral therapy. J Hepatol. 2006;44(1):47–55. https://doi.org/10.1016/j.jhep.2005.07.006.

    Article  CAS  PubMed  Google Scholar 

  99. Serfaty L, Capeau J. Hepatitis C, insulin resistance and diabetes: clinical and pathogenic data. Liver Int. 2009;29(Suppl 2):13–25. https://doi.org/10.1111/j.1478-3231.2008.01952.x.

    Article  CAS  PubMed  Google Scholar 

  100. Lo JC, Kazemi MR, Hsue PY, et al. The relationship between nucleoside analogue treatment duration, insulin resistance, and fasting arterialized lactate level in patients with HIV infection. Clin Infect Dis. 2005;41(9):1335–40. https://doi.org/10.1086/496981.

    Article  CAS  PubMed  Google Scholar 

  101. Hadigan C. Insulin resistance among HIV-infected patients: unraveling the mechanism. Clin Infect Dis. 2005;41(9):1341–2. https://doi.org/10.1086/496990.

    Article  PubMed  Google Scholar 

  102. • Reid M, Ma Y, Scherzer R, et al. Higher CD163 levels are associated with insulin resistance in hepatitis C virus-infected and HIV-infected adults. AIDS. 2017;31(3):385–93. https://doi.org/10.1097/QAD.0000000000001345Generation of insulin resistance in HIV/HCV co-infection may be mediated by microbial gut translocation triggering inflammatory signaling cascades as evidenced by higher sCD163 levels.

    Article  CAS  PubMed  Google Scholar 

  103. Brenchley JM, Price DA, Schacker TW, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006;12(12):1365–71. https://doi.org/10.1038/nm1511.

    Article  CAS  PubMed  Google Scholar 

  104. Grunfeld C, Feingold KR. The role of the cytokines, interferon alpha and tumor necrosis factor in the hypertriglyceridemia and wasting of AIDs. J Nutr. 1992;122(3 Suppl):749–53. https://doi.org/10.1093/jn/122.suppl_3.749.

    Article  CAS  PubMed  Google Scholar 

  105. Rose H, Hoy J, Woolley I, et al. HIV infection and high density lipoprotein metabolism. Atherosclerosis. 2008;199(1):79–86. https://doi.org/10.1016/j.atherosclerosis.2007.10.018.

    Article  CAS  PubMed  Google Scholar 

  106. 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. 2001;7(12):1327–31. https://doi.org/10.1038/nm1201-1327.

    Article  CAS  PubMed  Google Scholar 

  107. Kotler DP. HIV and antiretroviral therapy: lipid abnormalities and associated cardiovascular risk in HIV-infected patients. J Acquir Immune Defic Syndr. 2008;49(Suppl 2):S79–85. https://doi.org/10.1097/QAI.0b013e318186519c.

    Article  CAS  PubMed  Google Scholar 

  108. Babiker A, Jeudy J, Kligerman S, Khambaty M, Shah A, Bagchi S. Risk of Cardiovascular Disease Due to Chronic Hepatitis C Infection: A Review. J Clin Transl Hepatol. 2017;5(4):343–62. https://doi.org/10.14218/JCTH.2017.00021.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Petta S, Amato M, Cabibi D, et al. Visceral adiposity index is associated with histological findings and high viral load in patients with chronic hepatitis C due to genotype 1. Hepatology. 2010;52(5):1543–52. https://doi.org/10.1002/hep.23859.

    Article  PubMed  Google Scholar 

  110. Koethe JR, Hulgan T, Niswender K. Adipose Tissue and immune function: a review of evidence relevant to HIV infection. J Infect Dis. 2013;208(8):1194–201. https://doi.org/10.1093/infdis/jit324.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Lake JE. The fat of the matter: obesity and visceral adiposity in treated HIV infection. Curr HIV/AIDS Rep. 2017;14(6):211–9. https://doi.org/10.1007/s11904-017-0368-6.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Tien PC, Bacchetti P, Gripshover B, Overton ET, Rimland D, Kotler D. Association between hepatitis C virus coinfection and regional adipose tissue volume in HIV-infected men and women. J Acquir Immune Defic Syndr. 2007;45(1):60–5. https://doi.org/10.1097/QAI.0b013e3180423a95.

    Article  PubMed  PubMed Central  Google Scholar 

  113. • Breskin A, Westreich D, Cole SR, et al. The effects of hepatitis C infection and treatment on all-cause mortality among people living with human immunodeficiency virus. Clin Infect Dis. 2018. https://doi.org/10.1093/cid/ciy5Modeling the 10-year all-cause mortality in persons living with HIV after initiation of antiretroviral therapy showed a significant mortality benefit attributable to HCV elimination by direct-acting antivirals.

  114. Aberg JA, Gallant JE, Ghanem KG, et al. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014;58(1):1–10. https://doi.org/10.1093/cid/cit757.

    Article  PubMed  Google Scholar 

  115. Moyer VA. Preventive services task force. Screening and behavioral counseling interventions in primary care to reduce alcohol misuse: U.S. preventive services task force recommendation statement. Ann Intern Med. 2013;159(3):210–8. https://doi.org/10.7326/0003-4819-159-3-201308060-00652.

    Article  PubMed  Google Scholar 

  116. Guaraldi G, Orlando G, Zona S, et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis. 2011;53(11):1120–6. https://doi.org/10.1093/cid/cir627.

    Article  PubMed  Google Scholar 

  117. Rhee MK, Ho Y-L, Raghavan S, et al. Random plasma glucose predicts the diagnosis of diabetes. PLoS One. 2019;14(7):e0219964. https://doi.org/10.1371/journal.pone.0219964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Department of Health and Human Services. Available at http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf Accessed 24 Jul 2019.

  119. Adinolfi LE, Nevola R, Guerrera B, et al. Hepatitis C virus clearance by direct-acting antiviral treatments and impact on insulin resistance in chronic hepatitis C patients. J Gastroenterol Hepatol. 2018;33(7):1379–82. https://doi.org/10.1111/jgh.14067.

    Article  CAS  PubMed  Google Scholar 

  120. Hum J, Jou JH, Green PK, et al. Improvement in glycemic control of type 2 diabetes after successful treatment of hepatitis C virus. Diabetes Care. 2017;40(9):1173–80. https://doi.org/10.2337/dc17-0485.

    Article  CAS  PubMed  Google Scholar 

  121. Gastaldi G, Gomes D, Schneiter P, et al. Treatment with direct-acting antivirals improves peripheral insulin sensitivity in non-diabetic, lean chronic hepatitis C patients. PLoS One. 2019;14(6):e0217751. https://doi.org/10.1371/journal.pone.0217751.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Lim TR, Hazlehurst JM, Oprescu AI, et al. Hepatitis C virus infection is associated with hepatic and adipose tissue insulin resistance that improves after viral cure. Clin Endocrinol. 2019;90(3):440–8. https://doi.org/10.1111/cen.13924.

    Article  CAS  Google Scholar 

  123. Meissner EG, Lee Y-J, Osinusi A, et al. Effect of sofosbuvir and ribavirin treatment on peripheral and hepatic lipid metabolism in chronic hepatitis C virus, genotype 1-infected patients. Hepatology. 2015;61(3):790–801. https://doi.org/10.1002/hep.27424.

    Article  CAS  PubMed  Google Scholar 

  124. Beig J, Orr D, Harrison B, Gane E. Hepatitis C virus eradication with new interferon-free treatment improves metabolic profile in hepatitis C virus-related liver transplant recipients. Liver Transpl. 2018;24(8):1031–9. https://doi.org/10.1002/lt.25060.

    Article  PubMed  Google Scholar 

  125. Aboud M, Orkin C, Podzamczer D, et al. Efficacy and safety of dolutegravir-rilpivirine for maintenance of virological suppression in adults with HIV-1: 100-week data from the randomised, open-label, phase 3 SWORD-1 and SWORD-2 studies. Lancet HIV. 2019. https://doi.org/10.1016/S2352-3018(19)30149-3.

    Article  PubMed  Google Scholar 

Download references

Funding

The authors’ research activities are supported, in part, by grants from the National Institutes of Health/National Center for Advancing Translational Sciences (NCATS) (TL1TR002382, UL1TR002378).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lauren F. Collins MD.

Ethics declarations

Conflict of interest

Lauren F. Collins declares that she has no conflict of interest. Ruth O. Adekunle declares that she has no conflict of interest. Emily J. Cartwright declares that she has no conflict of interest.

Human and animal rights and informed consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Hepatitis C

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Collins, L.F., Adekunle, R.O. & Cartwright, E.J. Metabolic Syndrome in HIV/HCV Co-infected Patients. Curr Treat Options Infect Dis 11, 351–371 (2019). https://doi.org/10.1007/s40506-019-00207-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40506-019-00207-3

Keywords

Navigation