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Original article

Vol. 142 No. 0102 (2012)

Hepatitis C virus co-infection and sexual risk behaviour are associated with a high homocysteine serum level in HIV-infected patients

  • B Roca
  • M Bennasar
  • JA Ferrero
  • Monte del
  • E Resino
Cite this as:
Swiss Med Wkly. 2012;142:w13323


BACKGROUND AND AIMS: A better understanding of the relationship of homocysteine with cardiovascular risk factors is needed. The objectives of this study were to assess the serum level of homocysteine in HIV-infected patients and to analyse the possible association of increased levels of the amino acid with cardiovascular risk factors, demographic and clinical characteristics of participants.

METHODS: Cross-sectional study carried out as a supplementary task to the usual controls necessary in HIV-infected patients in the outpatient clinic of the Hospital General of Castellon, Spain. For two consecutive visits the demographic, clinical and HIV-related characteristics and blood analyses results were obtained for each participant. Homocysteine serum level was documented and the possible association of the amino acid with all the other study variables was assessed with a multiple linear regression analysis.

RESULTS: A total of 145 patients were included. The mean homocysteine serum level of all participants was 11.9 ± 5.9 µmol/L. A total of 54 patients (37%) presented homocysteine serum levels higher than the upper limit of normal. An association was found between higher homocysteine serum level and the following variables: family history of early coronary disease (P = 0.027), sexual HIV risk behaviour (P = 0.016), hepatitis C virus co-infection (P = 0.002), higher height (P = 0.002), higher diastolic blood pressure (P = 0.049), lower serum level of folic acid (P <0.001), and lower serum level of vitamin B12 (P = <0.001).

CONCLUSION: In the HIV population, increased homocysteine serum level is associated with sexual risk behaviour and hepatitis C virus coinfection.


  1. Buchacz K, Rangel M, Blacher R, Brooks JT. Changes in the Clinical Epidemiology of HIV Infection in the United States: Implications for the Clinician. Curr Infect Dis Rep. 2009;11:75–83.
  2. Fichtenbaum CJ. Metabolic Abnormalities Associated With HIV Infection and Antiretroviral Therapy. Curr Infect Dis Rep. 2009;11:84–92.
  3. The Data Collection on Adverse Events of Anti-HIV Drugs (DAD) Study Group. Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med. 2003;349:1993–2003.
  4. Domingo P, Suarez-Lozano I, Teira R, Lozano F, Terrón A, Viciana P, et al. Dyslipidemia and Cardiovascular Disease Risk Factor Management in HIV-1-Infected Subjects Treated with HAART in the Spanish VACH Cohort. Open AIDS J. 2008;2:26–38.
  5. Boccara F. Cardiovascular complications and atherosclerotic manifestations in the HIV-infected population: type, incidence and associated risk factors. AIDS. 2008;22(Suppl 3):S19–S26.
  6. McNulty H, Pentieva K, Hoey L, Ward M. Homocysteine, B-vitamins and CVD. Proc Nutr Soc. 2008;67:232–7.
  7. Wald DS, Wald NJ, Morris JK, Law M. Folic acid, homocysteine, and cardiovascular disease: judging causality in the face of inconclusive trial evidence. BMJ. 2006;333:1114–7.
  8. Humphrey LL, Fu R, Rogers K, Freeman M, Helfand M. Homocysteine level and coronary heart disease incidence: a systematic review and meta-analysis. Mayo Clin Proc. 2008;83:1203–12.
  9. Yang Q, Botto LD, Erickson JD, Berry RJ, Sambell C, Johansen H, et al. Improvement in stroke mortality in Canada and the United States, 1990 to 2002. Circulation. 2006;113:1335–43.
  10. Ebbing M, Bleie Ø, Ueland PM, Nordrehaug JE, Nilsen DW, Vollset SE, et al. Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial. JAMA. 2008;300:795–804.
  11. Albert CM, Cook NR, Gaziano JM, Zaharris E, MacFadyen J, Danielson E, et al. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial. JAMA. 2008;299:2027–36.
  12. Bonaa KH, Njolstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006;354:1578–88.
  13. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354:1567–77.
  14. Antoniades C, Antonopoulos AS, Tousoulis D, Marinou K, Stefanadis C. Homocysteine and coronary atherosclerosis: from folate fortification to the recent clinical trials. Eur Heart J. 2008;30:6–15.
  15. Selhub J. Public health significance of elevated homocysteine. Food Nutr Bull. 2008;29(2 Suppl):S116–S125.
  16. 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. November 3, 2008; 1-139. Available at Accessed January 22, 2009.
  17. Guaraldi G, Ventura P, Garlassi E, Orlando G, Squillace N, Nardini G, et al. Hyperhomocysteinaemia in HIV-infected patients: determinants of variability and correlations with predictors of cardiovascular disease. HIV Med. 2009;10:28–34.
  18. Bernasconi E, Uhr M, Magenta L, Ranno A, Telenti A. Homocysteinaemia in HIV-infected patients treated with highly active antiretroviral therapy. The Swiss HIV Cohort Study. AIDS. 2001;15:1081–2.
  19. Bongiovanni M, Casana M, Pisacreta M, Tordato F, Cicconi P, Russo U, et al. Predictive factors of hyperhomocysteinemia in HIV-positive patients. J Acquir Immune Defic Syndr. 2007;44:117–9.
  20. Uccelli MC, Torti C, Lapadula G, Labate L, Cologni G, Tirelli V, et al. Influence of folate serum concentration on plasma homocysteine levels in HIV-positive patients exposed to protease inhibitors undergoing HAART. Ann Nutr Metab. 2006;50:247–52.
  21. Başkan BM, Sivas F, Aktekin LA, Doğan YP, Ozoran K, Bodur H. Serum homocysteine level in patients with ankylosing spondylitis. Rheumatol Int. 2009;29:1435–9.
  22. Fimognari FL, Loffredo L, Di Simone S, Sampietro F, Pastorelli R, Monaldo M, et al. Hyperhomocysteinaemia and poor vitamin B status in chronic obstructive pulmonary disease. Nutr Metab Cardiovasc Dis. 2009;19:654–9.
  23. Fujimaki C, Hayashi H, Tsuboi S, Matsuyama T, Kosuge K, Yamada H, et al. Plasma total homocysteine level and methylenetetrahydrofolate reductase 677C>T genetic polymorphism in Japanese patients with rheumatoid arthritis. Biomarkers. 2009;14:49–54.
  24. de Bree A, van der Put NM, Mennen LI, Verschuren WM, Blom HJ, Galan P, et al. Prevalences of hyperhomocysteinemia, unfavourable cholesterol profile and hypertension in European populations. Eur J Clin Nutr. 2005;59:480–8.
  25. Roca B, Suarez I, Gonzalez J, Garrido M, de la Fuente B, Teira R, et al. Hepatitis C virus and human immunodeficiency virus coinfection in Spain. J Infect. 2003;47:117–24.
  26. Fu M, Martínez-Sánchez JM, Pérez-Ríos M, López MJ, Fernández E. A comparison of the Fagerström test for nicotine dependence and smoking prevalence across countries: updated data from Spain. Addiction. 2009;104:326–7.
  27. Graham I, Atar D, Borch-Johnsen K, Boysen G, Burell G, Cifkova R, et al.; European Society of Cardiology (ESC); European Association for Cardiovascular Prevention and Rehabilitation (EACPR); Council on Cardiovascular Nursing; European Association for Study of Diabetes (EASD); International Diabetes Federation Europe (IDF-Europe); European Stroke Initiative (EUSI); Society of Behavioural Medicine (ISBM); European Society of Hypertension (ESH); WONCA Europe (European Society of General Practice/Family Medicine); European Heart Network (EHN); European Atherosclerosis Society (EAS). European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice. Eur J Cardiovasc Prev Rehabil. 2007;14(Suppl 2):S1–S113.
  28. Herrero JI, Quiroga J, Sangro B, Beloqui O, Pardo F, Cienfuegos JA, et al. Hyperhomocysteinaemia in liver transplant recipients: prevalence and multivariate analysis of predisposing factors. Liver Transpl. 2000;6:614–8.
  29. Bernhard MC, Junker E, Hettinger A, Lauterburg BH. Time course of total cysteine, glutathione and homocysteine in plasma of patients with chronic hepatitis C treated with interferon-alpha with and without supplementation with N-acetylcysteine. J Hepatol. 1998;28:751–5.
  30. Adinolfi LE, Ingrosso D, Cesaro G, Cimmino A, D’Antò M, Capasso R, et al. Hyperhomocysteinaemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients. Hepatology. 2005;41:995–1003.
  31. Roblin X, Pofelski J, Zarski JP. Role de l’homocysteine au cours de la steatose hepatique et de l’hepatite chronique C. Gastroenterol Clin Biol. 2007;31:415–20.
  32. Toniutto P, Fabris C, Falleti E, Cussigh A, Fontanini E, Bitetto D, et al. Methylenetetrahydrofolate reductase C677T polymorphism and liver fibrosis progression in patients with recurrent hepatitis C. Liver Int. 2008;28:257–63.
  33. Borgia G, Gentile I, Fortunato G, Borrelli F, Borelli S, de Caterina M, et al. Homocysteine levels and sustained virological response to pegylated-interferon alpha2b plus ribavirin therapy for chronic hepatitis C: a prospective study. Liver Int. 2009;29:248–52.
  34. De Larrañaga G, Alonso B, Puga L, Benetucci J. Homocisteína plasmática en infectados con el virus de la inmunodeficiencia humana. Medicina (B Aires) 2003;63:393–8.
  35. Ganji V, Kafai MR. Demographic, lifestyle, and health characteristics and serum B vitamin status are determinants of plasma total homocysteine concentration in the post-folic acid fortification period, 1999–2004. J Nutr. 2009;139:345–52.
  36. Raiszadeh F, Hoover DR, Lee I, Shi Q, Anastos K, Gao W, et al. Plasma Homocysteine is not associated with HIV serostatus or antiretroviral therapy in women. J Acquir Immune Defic Syndr. 2009;51:175–8.
  37. Smulders YM, Spoelstra-de Man AM, Slaats EH, Weigel HM, Stehouwer CD, Jos Frissen PH. Trimethoprim-sulphamethoxazole as primary Pneumocystis carinii prophylaxis does not increase serum homocysteine levels in HIV-positive subjects. Eur J Intern Med. 2001;12:363–5.
  38. Gonvers JJ, Heim MH, Cavassini M, Müllhaupt B, Genné D, et al. Treatment of hepatitis C in HCV mono-infected and in HIV-HCV co-infected patients: an open-labelled comparison study. Swiss Med Wkly. 2010;140:w13055. doi: 10.4414/smw.2010.13055.