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Original article

Vol. 140 No. 2930 (2010)

Treatment of hepatitis C in HCV mono-infected and in HIV-HCV co-infected patients: an open-labelled comparison study

  • D Genné
  • J Borovicka
  • A Cerny
  • C Chuard
  • V Dutoit
  • R Malinverni
  • B Müllhaupt
  • M Monnat
  • F Negro
  • C Oneta
  • JP Chave
  • JF Dufour
  • JJ Gonvers
  • MH Heim
DOI
https://doi.org/10.4414/smw.2010.13055
Cite this as:
Swiss Med Wkly. 2010;140:w13055
Published
19.07.2010

Summary

Background/aims: Treatment of chronic HCV infection has become a priority in HIV+ patients, given the faster progression to end-stage liver disease. The primary endpoint of this study was to evaluate and compare antiviral efficacy of Peginterferon alpha 2a plus ribavirin in HIV-HCV co-infected and HCV mono-infected patients, and to examine whether 6 months of therapy would have the same efficacy in HIV patients with favourable genotypes 2 and 3 as in mono-infected patients, to minimise HCV-therapy-related toxicities. Secondary endpoints were to evaluate predictors of sustained virological response (SVR) and frequency of side-effects.

Methods: Patients with genotypes 1 and 4 were treated for 48 weeks with Pegasys® 180 µg/week plus Copegus® 1000–1200 mg/day according to body weight; patients with genotypes 2 and 3 for 24 weeks with Pegasys® 180 µg/week plus Copegus® 800 mg/day.

Results: 132 patients were enrolled in the study: 85 HCV mono-infected (38: genotypes 1 and 4; 47: genotypes 2 and 3), 47 HIV-HCV co-infected patients (23: genotypes 1 and 4; 24: genotypes 2 and 3). In an intention-to-treat analysis, SVR for genotypes 1 and 4 was observed in 58% of HCV mono-infected and in 13% of HIV-HCV co-infected patients (P = 0.001). For genotypes 2 and 3, SVR was observed in 70% of HCV mono-infected and in 67% of HIV-HCV co-infected patients (P = 0.973). Undetectable HCV-RNA at week 4 had a positive predictive value for SVR for mono-infected patients with genotypes 1 and 4 of 0.78 (95% CI: 0.54–0.93) and of 0.81 (95% CI: 0.64–0.92) for genotypes 2 and 3. For co-infected patients with genotypes 2 and 3, the positive predictive value of SVR of undetectable HCV-RNA at week 4 was 0.76 (95%CI, 0.50–0.93). Study not completed by 22 patients (36%): genotypes 1 and 4 and by 12 patients (17%): genotypes 2 and 3.

Conclusion: Genotypes 2 or 3 predict the likelihood of SVR in HCV mono-infected and in HIV-HCV co-infected patients. A 6-month treatment with Peginterferon alpha 2a plus ribavirin has the same efficacy in HIV-HCV co-infected patients with genotypes 2 and 3 as in mono-infected patients. HCV-RNA negativity at 4 weeks has a positive predictive value for SVR. Aggressive treatment of adverse effects to avoid dose reduction, consent withdrawal or drop-out is crucial to increase the rate of SVR, especially when duration of treatment is 48 weeks. Sixty-one percent of HIV-HCV co-infected patients with genotypes 1 and 4 did not complete the study against 4% with genotypes 2 and 3.

References

  1. Rauch A, Rickenbach M, Weber R, et al. Unsafe sex and increased incidence of hepatitis C virus infection among HIV-infected men who have sex with men: the Swiss HIV Cohort Study. Clin Infect Dis. 2005;41:395–402.
  2. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet. 2008;372:293–9.
  3. Weber R, Sabin CA, Friis-Moller N, et al. Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study. Arch Intern Med. 2006;166:1632–41.
  4. Berenguer J, Alvarez-Pellicer J, Martin PM, et al. Sustained virological response to interferon plus ribavirin reduces liver-related complications and mortality in patients coinfected with human immunodeficiency virus and hepatitis C virus. Hepatology. 2009;50:407–13.
  5. Carrat F, Bani-Sadr F, Pol S, et al. Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. JAMA. 2004;292:2839–48.
  6. Chung RT, Andersen J, Volberding P, et al. Peginterferon Alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med. 2004;351:451–9.
  7. Nunez M, Marino A, Miralles C, et al. Baseline serum hepatitis C virus (HCV) RNA level and response at week 4 are the best predictors of relapse after treatment with pegylated interferon plus ribavirin in HIV/HCV-coinfected patients. J Acquir Immune Defic Syndr. 2007;45:439–44.
  8. Torriani FJ, Rodriguez-Torres M, Rockstroh JK, et al. Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med. 2004;351:438–50.
  9. Davis GL, Wong JB, McHutchison JG, et al. Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology. 2003;38:645–52.
  10. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975–82.
  11. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958–65.
  12. Fried MW, Hadziyannis SJ, Shiffman M, et al. Rapid viral response is a more important predictor of sustained virological response (SVR) than genotype in patients with chronic hepatitis C virus infection. J Hepatol. 2008;48(Suppl.2):5A.
  13. Payan C, Pivert A, Morand P, et al. Rapid and early virological response to chronic hepatitis C treatment with IFN alpha2b or PEG-IFN alpha2b plus ribavirin in HIV/HCV co-infected patients. Gut. 2007;56:1111–6.
  14. Alberti A, Clumeck N, Collins S, et al. Short statement of the first European Consensus Conference on the treatment of chronic hepatitis B and C in HIV co-infected patients. J Hepatol. 2005;42:615–24.
  15. Dhumeaux D, Marcellin P, Lerebours E. Treatment of hepatitis C. The 2002 French consensus. Gut. 2003;52:1784–7.
  16. Strader DB, Wright T, Thomas DL, et al. Diagnosis, management, and treatment of hepatitis C. Hepatology. 2004;39:1147–71.
  17. Ware JE Jr, Snow K, Kosinski M, et al. SF-36 Health Survey: Manual and Interpretation Guide. The Health Institute, New England Medical Center, Boston, Massachusetts 1993.
  18. Ware JE Jr, Kosinski M, Keller S. Physical and Mental Health Summary Scores: A User’s Manual. The Health Institute, New England Medical Center, Boston, Massachusetts 1994.
  19. Bonkovsky HL, Woolley JM. Reduction of health-related quality of life in chronic hepatitis C and improvement with interferon therapy.The Consensus Interferon Study Group. Hepatology. 1999;29:264–70.
  20. Call SA, Klapow JC, Stewart KE, et al. Health-related quality of life and virologic outcomes in an HIV clinic. Qual Life Res. 2000;9:977–85.
  21. Fleming CA, Christiansen D, Nunes D, et al. Health-related quality of life of patients with HIV disease: impact of hepatitis C coinfection. Clin Infect Dis. 2004;38:572–8.
  22. Foster GR. Hepatitis C virus infection: quality of life and side effects of treatment. J Hepatol. 1999;31(Suppl 1):250–4.
  23. Spiegel BM, Younossi ZM, Hays RD, et al. Impact of hepatitis C on health related quality of life: a systematic review and quantitative assessment. Hepatology. 2005;41:790–800.
  24. Ware JE Jr, Bayliss MS, Mannocchia M, et al. Health-related quality of life in chronic hepatitis C: impact of disease and treatment response. The Interventional Therapy Group. Hepatology. 1999;30:550–5.
  25. Soriano V, Maida I, Nunez M, et al. Long-term follow-up of HIV-infected patients with chronic hepatitis C virus infection treated with interferon-based therapies. Antivir Ther. 2004;9:987–92.
  26. Veldt BJ, Heathcote EJ, Wedemeyer H, et al. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Ann Intern Med. 2007;147:677–84.
  27. Hadziyannis SJ, Sette H Jr, Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140:346–55.
  28. Nunez M, Miralles C, Berdun MA, et al. Role of weight-based ribavirin dosing and extended duration of therapy in chronic hepatitis C in HIV-infected patients: the PRESCO trial. AIDS Res Hum Retroviruses. 2007;23:972–82.
  29. Perez-Olmeda M, Nunez M, Romero M, et al. Pegylated IFN-alpha2b plus ribavirin as therapy for chronic hepatitis C in HIV-infected patients. Aids. 2003;17:1023–8.
  30. Torriani FJ, Ribeiro RM, Gilbert TL, et al. Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) dynamics during HCV treatment in HCV/HIV coinfection. J Infect Dis. 2003;188:1498–507.
  31. Jacobson IM, Brown RS, Jr., Freilich B, et al. Peginterferon alfa-2b and weight-based or flat-dose ribavirin in chronic hepatitis C patients: a randomized trial. Hepatology. 2007;46:971–81.
  32. Poynard T, McHutchison J, Goodman Z, et al. Is an “a la carte” combination interferon alfa-2b plus ribavirin regimen possible for the first line treatment in patients with chronic hepatitis C? The ALGOVIRC Project Group. Hepatology. 2000;31:211–8.
  33. Shiffman ML, Suter F, Bacon BR, et al. Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2007;357:124–34.
  34. Dieterich DT, Duff F, Sulkowski M, et al. Sustained virologic response (SVR) in HIV/HCV coinfected patients with HCV genotype 1 infection who have a rapid virologic response at week four of treatment with peginterferon alfa-2a plus ribavirin. Presented at the 13th annual Conference on Retroviruses and Opportunistic Infections, Denver, CO, February 5–8, 2006; abstract #856. 2006.
  35. Crespo M, Sauleda S, Esteban JI, et al. Peginterferon alpha-2b plus ribavirin vs interferon alpha-2b plus ribavirin for chronic hepatitis C in HIV-coinfected patients. J Viral Hepat. 2007;14:228–38.
  36. Rockstroh JK, Bhagani S, Benhamou Y, et al. European AIDS Clinical Society (EACS) guidelines for the clinical management and treatment of chronic hepatitis B and C coinfection in HIV-infected adults. HIV Med. 2008;9:82–8.
  37. Berg T, Sarrazin C, Herrmann E, et al. Prediction of treatment outcome in patients with chronic hepatitis C: significance of baseline parameters and viral dynamics during therapy. Hepatology. 2003;37:600–9.
  38. Berg T, von Wagner M, Nasser S, et al. Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin. Gastroenterology. 2006;130:1086–97.
  39. Poynard T, Marcellin P, Lee SS, et al. Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT). Lancet. 1998;352:1426–32.
  40. Zeuzem S, Buti M, Ferenci P, et al. Efficacy of 24 weeks treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C infected with genotype 1 and low pretreatment viremia. J Hepatol. 2006;44:97–103.
  41. Zeuzem S, Hultcrantz R, Bourliere M, et al. Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3. J Hepatol. 2004;40:993–9.
  42. Dore GJ, Torriani FJ, Rodriguez-Torres M, et al. Baseline factors prognostic of sustained virological response in patients with HIV-hepatitis C virus co-infection. Aids. 2007;21:1555–9.
  43. Bernstein D, Kleinman L, Barker CM, et al. Relationship of health-related quality of life to treatment adherence and sustained response in chronic hepatitis C patients. Hepatology. 2002;35:704–8.
  44. Foster GR, Goldin RD, Thomas HC. Chronic hepatitis C virus infection causes a significant reduction in quality of life in the absence of cirrhosis. Hepatology. 1998;27:209–12.
  45. Hauser W, Zimmer C, Schiedermaier P, et al. Biopsychosocial predictors of health-related quality of life in patients with chronic hepatitis C. Psychosom Med. 2004;66:954–8.
  46. Helbling B, Overbeck K, Gonvers JJ, et al. Host- rather than virus-related factors reduce health-related quality of life in hepatitis C virus infection. Gut. 2008;57:1597–603.
  47. Kramer L, Hofer H, Bauer E, et al. Relative impact of fatigue and subclinical cognitive brain dysfunction on health-related quality of life in chronic hepatitis C infection. Aids. 2005;19(Suppl 3):S85–92.
  48. Rodger AJ, Jolley D, Thompson SC, et al. The impact of diagnosis of hepatitis C virus on quality of life. Hepatology. 1999;30:1299–301.
  49. von Wagner M, Lee JH, Kronenberger B, et al. Impaired health-related quality of life in patients with chronic hepatitis C and persistently normal aminotransferase levels. J Viral Hepat. 2006;13:828-34.
  50. Hays RD, Cunningham WE, Sherbourne CD, et al. Health-related quality of life in patients with human immunodeficiency virus infection in the United States: results from the HIV Cost and Services Utilization Study. Am J Med. 2000;108:714–22.
  51. Miners AH, Sabin CA, Mocroft A, et al. Health-related quality of life in individuals infected with HIV in the era of HAART. HIV Clin Trials. 2001;2:484–92.
  52. Sherbourne CD, Hays RD, Fleishman JA, et al. Impact of psychiatric conditions on health-related quality of life in persons with HIV infection. Am J Psychiatry. 2000;157:248–54.