Current Infectious Disease Reports

, Volume 7, Issue 2, pp 91–102 | Cite as

Management of hepatitis C in HIV-infected patients

  • Benigno Rodriguez
  • David A. Bobak
Article

Abstract

As the survival of HIV-infected patients has been lengthening over the past 10 years as a consequence of effective antiretroviral therapy, hepatitis C virus (HCV) coinfection has emerged as a major cause of morbidity and mortality in this population. HCV/HIV coinfection is associated with accelerated progression of liver disease, untoward effects on the immunologic and virologic response to antiretroviral medications, and possibly with a more aggressive course of HIV disease. The results of major trials of combination therapy for HCV in coinfected patients have clearly established the combination of pegylated interferon-α with ribavirin as the treatment of choice in this population. However, the effectiveness and tolerability of this regimen remains suboptimal, particularly in patients with genotype 1 HCV infection. This paper reviews the impact of HCV coinfection in HIV-infected patients, outlines current concepts on management and antiviral treatment, and discusses some of the newer agents, currently in the therapeutic pipeline, that are directed against novel molecular targets.

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References and Recommended Reading

  1. 1.
    World Health Organization: Hepatitis C--global prevalence (update). Wkly Epidemiol Rec 1999, 74:425–427.Google Scholar
  2. 2.
    Alter MJ, Kruszon-Moran D, Nainan OV, et al.: The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med 1999, 341:556–562.PubMedCrossRefGoogle Scholar
  3. 3.
    Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. Centers for Disease Control and Prevention. MMWR Recomm Rep 1998, 47:1–39.Google Scholar
  4. 4.
    Palella FJ Jr, Delaney KM, Moorman AC, et al.: Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998, 338:853–860.PubMedCrossRefGoogle Scholar
  5. 5.
    Murphy EL, Collier AC, Kalish LA, et al.: Highly active antiretroviral therapy decreases mortality and morbidity in patients with advanced HIV disease. Ann Intern Med 2001, 135:17–26.PubMedGoogle Scholar
  6. 6.
    Soriano V, Garcia-Samaniego J, Valencia E, et al.: Impact of chronic liver disease due to hepatitis viruses as cause of hospital admission and death in HIV-infected drug users. Eur J Epidemiol 1999, 15:1–4.PubMedCrossRefGoogle Scholar
  7. 7.
    Macias J, Pineda JA, Leal M, et al.: Influence of hepatitis C virus infection on the mortality of antiretroviral-treated patients with HIV disease. Eur J Clin Microbiol Infect Dis 1998, 17:167–170.PubMedCrossRefGoogle Scholar
  8. 8.
    Bica I, McGovern B, Dhar R, et al.: Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection. Clin Infect Dis 2001, 32:492–497.PubMedCrossRefGoogle Scholar
  9. 9.
    Martin-Carbonero L, Soriano V, Valencia E, et al.: Increasing impact of chronic viral hepatitis on hospital admissions and mortality among HIV-infected patients. AIDS Res Hum Retroviruses 2001, 17:1467–1471.PubMedCrossRefGoogle Scholar
  10. 10.
    Selik RM, Byers RH Jr, Dworkin MS: Trends in diseases reported on U.S. death certificates that mentioned HIV infection, 1987–1999. J Acquir Immune Defic Syndr 2002, 29:378–387.PubMedGoogle Scholar
  11. 11.
    Eyster ME, Fried MW, Di Bisceglie AM, Goedert JJ: Increasing hepatitis C virus RNA levels in hemophiliacs: relationship to human immunodeficiency virus infection and liver disease. Multicenter Hemophilia Cohort Study. Blood 1994, 84:1020–1023.PubMedGoogle Scholar
  12. 12.
    Benhamou Y, Bochet M, Di Martino V, et al.: Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. The Multivirc Group. Hepatology 1999, 30:1054–1058.PubMedCrossRefGoogle Scholar
  13. 13.
    Rockstroh JK, Spengler U, Sudhop T, et al.: Immunosuppression may lead to progression of hepatitis C virus-associated liver disease in hemophiliacs coinfected with HIV. Am J Gastroenterol 1996, 91:2563–2568.PubMedGoogle Scholar
  14. 14.
    Puoti M, Bonacini M, Spinetti A, et al.: Liver fibrosis progression is related to CD4 cell depletion in patients coinfected with hepatitis C virus and human immunodeficiency virus. J Infect Dis 2001, 183:134–137.PubMedCrossRefGoogle Scholar
  15. 15.
    Greub G, Ledergerber B, Battegay M, et al.: Clinical progression, survival, and immune recovery during antiretroviral therapy in patients with HIV-1 and hepatitis C virus coinfection: the Swiss HIV Cohort Study. Lancet 2000, 356:1800–1805. This is a large study that examined the impact of HCV coinfection on HIV disease and found that coinfected patients had an increased risk of HIV disease progression and a lower degree of CD4+ T-cell recovery after successful HAART.PubMedCrossRefGoogle Scholar
  16. 16.
    Bruno R, Sacchi P, Filice C, et al.: Hepatocellular carcinoma in HIV-infected patients with chronic hepatitis: an emerging issue. J Acquir Immune Defic Syndr 2002, 30:535–536.PubMedGoogle Scholar
  17. 17.
    Di Martino V, Rufat P, Boyer N, et al.: The influence of human immunodeficiency virus coinfection on chronic hepatitis C in injection drug users: a long-term retrospective cohort study. Hepatology 2001, 34:1193–1199.PubMedCrossRefGoogle Scholar
  18. 18.
    Monforte Ade A, Bugarini R, Pezzotti P, et al.: Low frequency of severe hepatotoxicity and association with HCV coinfection in HIV-positive patients treated with HAART. J Acquir Immune Defic Syndr 2001, 28:114–123.PubMedCrossRefGoogle Scholar
  19. 19.
    Ammassari A, Trotta MP, Cozzi-Lepri A, et al.: Hepatitis C virus co-infection increases risk of non-adherence to highly active antiretroviral therapy (HAART) in HIV-infected persons [abstract 793]. Paper presented at the 55th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, MA, October 29-November 2, 2004.Google Scholar
  20. 20.
    Melvin DC, Lee JK, Belsey E, et al.: The impact of coinfection with hepatitis C virus and HIV on the tolerability of antiretroviral therapy. AIDS 2000, 14:463–465.PubMedCrossRefGoogle Scholar
  21. 21.
    Fleming CA, Craven DE, Thornton D, et al.: Hepatitis C virus and human immunodeficiency virus coinfection in an urban population: low eligibility for interferon treatment. Clin Infect Dis 2003, 36:97–100.PubMedCrossRefGoogle Scholar
  22. 22.
    Sherman KE, Rouster SD, Chung RT, Rajicic N: Hepatitis C virus prevalence among patients infected with human immunodeficiency virus: a cross-sectional analysis of the US Adult AIDS Clinical Trials Group. Clin Infect Dis 2002, 34:831–837.PubMedCrossRefGoogle Scholar
  23. 23.
    Bove JR: Transfusion-associated hepatitis and AIDS. What is the risk? N Engl J Med 1987, 317:242–245.PubMedCrossRefGoogle Scholar
  24. 24.
    Darby SC, Ewart DW, Giangrande PL, et al.: Mortality from liver cancer and liver disease in haemophilic men and boys in UK given blood products contaminated with hepatitis C. UK Haemophilia Centre Directors’ Organisation. Lancet 1997, 350:1425–1431.PubMedCrossRefGoogle Scholar
  25. 25.
    Rauch A, Rickenbach M, Weber R, et al.: Incidence of hepatitis C virus infection in the Swiss HIV Cohort Study [ abstract MoPeB3335]. Paper presented at the XV International AIDS Conference. Bangkok, Thailand, July 11–16, 2004.Google Scholar
  26. 26.
    Staples CT Jr, 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, 29:150–154.PubMedGoogle Scholar
  27. 27.
    Mathei C, Buntinx F, van Damme P: Seroprevalence of hepatitis C markers among intravenous drug users in western European countries: a systematic review. J Viral Hepat 2002, 9:157–173.PubMedCrossRefGoogle Scholar
  28. 28.
    Roy K, Hay G, Andragetti R, Taylor A, et al.: Monitoring hepatitis C virus infection among injecting drug users in the European Union: a review of the literature. Epidemiol Infect 2002, 129:577–585.PubMedCrossRefGoogle Scholar
  29. 29.
    Yee TT, Griffioen A, Sabin CA, et al.: The natural history of HCV in a cohort of haemophilic patients infected between 1961 and 1985. Gut 2000, 47:845–851.PubMedCrossRefGoogle Scholar
  30. 30.
    Thomas DL, Astemborski J, Rai RM, et al.: The natural history of hepatitis C virus infection: host, viral, and environmental factors. JAMA 2000, 284:450–456.PubMedCrossRefGoogle Scholar
  31. 31.
    Bonacini M, Lin HJ, Hollinger FB: Effect of coexisting HIV-1 infection on the diagnosis and evaluation of hepatitis C virus. J Acquir Immune Defic Syndr 2001, 26:340–344.PubMedGoogle Scholar
  32. 32.
    Daar ES, Lynn H, Donfield S,et al.: Relation between HIV-1 and hepatitis C viral load in patients with hemophilia. J Acquir Immune Defic Syndr 2001, 26:466–472.PubMedGoogle Scholar
  33. 33.
    Gibb DM, Goodall RL, Dunn DT, et al.: Mother-to-child transmission of hepatitis C virus: evidence for preventable peripartum transmission. Lancet 2000, 356:904–907.PubMedCrossRefGoogle Scholar
  34. 34.
    Zanetti AR, Tanzi E, Romano L, et al.: Multicenter trial on mother-to-infant transmission of GBV-C virus. The Lombardy Study Group on VerticalJPerinatal Hepatitis Viruses Transmission. J Med Virol 1998, 54:107–112.PubMedCrossRefGoogle Scholar
  35. 35.
    Thomas DL, Villano SA, Riester KA, et al.: Perinatal transmission of hepatitis C virus from human immunodeficiency virus type 1-infected mothers. Women and Infants Transmission Study. J Infect Dis 1998, 177:1480–1488.PubMedGoogle Scholar
  36. 36.
    Eyster ME, Alter HJ, Aledort LM, et al.: Heterosexual co-transmission of hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Ann Intern Med 1991, 115:764–768.PubMedGoogle Scholar
  37. 37.
    Thomas DL, Shih JW, Alter HJ, et al.: Effect of human immunodeficiency virus on hepatitis C virus infection among injecting drug users. J Infect Dis 1996, 174:690–695.PubMedGoogle Scholar
  38. 38.
    Serfaty L, Costagliola D, Wendum D, et al.: Impact of early-untreated HIV infection on chronic hepatitis C in intravenous drug users: a case-control study. AIDS 2001, 15:2011–2016.PubMedCrossRefGoogle Scholar
  39. 39.
    Giordano TP, Kramer JR, Souchek J, et al.: Does HCV co-infection increase the incidence of non-alcoholic cirrhosis and hepatocellular carcinoma? A cohort study of HIV-infected US Veterans, 1992–2001 [abstract 213]. Paper presented at the 2nd IAS Conference on HIV Pathogenesis and Treatment. Paris, July 2003. AntivirTher 2003, 8(Suppl 1):S235.Google Scholar
  40. 40.
    Eyster ME, Diamondstone LS, Lien JM, et al.: Natural history of hepatitis C virus infection in multitransfused hemophiliacs: effect of coinfection with human immunodeficiency virus. The Multicenter Hemophilia Cohort Study. J Acquir Immune Defic Syndr 1993, 6:602–610.PubMedGoogle Scholar
  41. 41.
    Ragni MV, Belle SH: Impact of human immunodeficiency virus infection on progression to end-stage liver disease in individuals with hemophilia and hepatitis C virus infection. J Infect Dis 2001, 183:1112–1115.PubMedCrossRefGoogle Scholar
  42. 42.
    Soto B, Sanchez-Quijano A, Rodrigo L, et al.: Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis. J Hepatol 1997, 26:1–5.PubMedCrossRefGoogle Scholar
  43. 43.
    Cacoub P, Geffray L, Rosenthal E, et al.: Mortality among human immunodeficiency virus-infected patients with cirrhosis or hepatocellular carcinoma due to hepatitis C virus in French Departments of Internal Medicine/ Infectious Diseases, in 1995 and 1997. Clin Infect Dis 2001, 32:1207–1214.PubMedCrossRefGoogle Scholar
  44. 44.
    Macias J, Melguizo I, Fernandez-Rivera FJ, et al.: Mortality due to liver failure and impact on survival of hepatitis virus infections in HIV-infected patients receiving potent antiretroviral therapy. Eur J Clin Microbiol Infect Dis 2002, 21:775–781.PubMedCrossRefGoogle Scholar
  45. 45.
    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, 33:562–569. This is a meta-analysis of eight studies, including 601 HIVJHCV-coinfected patients and 1370 singly HCV infected patients, which demonstrated that HIV coinfection is associated with an increased risk of histological cirrhosis and decompensated liver disease.PubMedCrossRefGoogle Scholar
  46. 46.
    Fultz SL, Chang CC, Skanderson M, et al.: Survival in patients coinfected with HIV and hepatitis C in the HAART era [abstract MoPeB3318]. Paper presented at the XV International AIDS Conference. Bangkok, Thailand, July 11–16, 2004.Google Scholar
  47. 47.
    Sabin CA, Telfer P, Phillips AN, et al.: The association between hepatitis C virus genotype and human immunodeficiency virus disease progression in a cohort of hemophilic men. J Infect Dis 1997, 175:164–168.PubMedGoogle Scholar
  48. 48.
    Piroth L, Duong M, Quantin C, et al.: Does hepatitis C virus co-infection accelerate clinical and immunological evolution of HIV-infected patients? AIDS 1998, 12:381–388.PubMedCrossRefGoogle Scholar
  49. 49.
    Dorrucci M, Pezzotti P, Phillips AN, et al.: Coinfection of hepatitis C virus with human immunodeficiency virus and progression to AIDS. Italian Seroconversion Study. J Infect Dis 1995, 172:1503–1508.PubMedGoogle Scholar
  50. 50.
    Quan CM, Krajden M, Grigoriew GA, Salit IE: Hepatitis C virus infection in patients infected with the human immunodeficiency virus. Clin Infect Dis 1993, 17:117–119.PubMedGoogle Scholar
  51. 51.
    Wright TL, Hollander H, Pu X, et al.: Hepatitis C in HIV-infected patients with and without AIDS: prevalence and relationship to patient survival. Hepatology 1994, 20:1152–1155.PubMedCrossRefGoogle Scholar
  52. 52.
    Sulkowski MS, Moore RD, Mehta SH, et al.: Hepatitis C and progression of HIV disease. JAMA 2002, 288:199–206. This is a major observational study of the effect of HCV coinfection on HIV disease progression, which failed to identify a consistent adverse impact of coinfection on risk of AIDS-defining events or immune reconstitution after HAART.PubMedCrossRefGoogle Scholar
  53. 53.
    Rancinan C, Neau D, Saves M, et al.: Is hepatitis C virus co-infection associated with survival in HIV-infected patients treated by combination antiretroviral therapy? AIDS 2002, 16:1357–1362.PubMedCrossRefGoogle Scholar
  54. 54.
    Tedaldi EM, Baker RK, Moorman AC, et al.: 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 InfectDis 2003, 36:363–367.CrossRefGoogle Scholar
  55. 55.
    Sulkowski MS, Thomas DL, Chaisson RE, Moore RD: Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection. JAMA 2000, 283:74–80.PubMedCrossRefGoogle Scholar
  56. 56.
    den Brinker M, Wit FW, Wertheim-van Dillen PM, et al.: Hepatitis B and C virus co-infection and the risk for hepatotoxicity of highly active antiretroviral therapy in HIV-1 infection. AIDS 2000, 14:2895–2902.CrossRefGoogle Scholar
  57. 57.
    Qurishi N, Kreuzberg C, Luchters G, et al.: Effect of antiretroviral therapy on liver-related mortality in patients with HIV and hepatitis C virus coinfection. Lancet 2003, 362:1708–1713.PubMedCrossRefGoogle Scholar
  58. 58.
    Sabin CA, Walker AS, Dunn D: HIVJHCV coinfection, HAART, and liver-related mortality. Lancet 2004, 364:757–758; author reply 758.PubMedCrossRefGoogle Scholar
  59. 59.
    John M, Flexman J, French MA: Hepatitis C virus-associated hepatitis following treatment of HIV-infected patients with HIV protease inhibitors: an immune restoration disease? AIDS 1998, 12:2289–2293.PubMedCrossRefGoogle Scholar
  60. 60.
    Martin-Carbonero L, Nunez M, Rios P, et al.: Liver injury after beginning antiretroviral therapy in HIVJhepatitis C virus co-infected patients is not related to immune reconstitution. AIDS 2002, 16:1423–1425.PubMedCrossRefGoogle Scholar
  61. 61.
    Kottilil S, Polis MA, Kovacs JA: HIV Infection, hepatitis C infection, and HAART: hard clinical choices. JAMA 2004, 292:243–250.PubMedCrossRefGoogle Scholar
  62. 62.
    Sulkowski MS, Thomas DL: Hepatitis C in the HIV-infected person. Ann Intern Med 2003, 138:197–207.PubMedGoogle Scholar
  63. 63.
    Sulkowski MS, Thomas DL, Mehta SH, et al.: Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: role of hepatitis C and B infections. Hepatology 2002, 35:182–189.PubMedCrossRefGoogle Scholar
  64. 64.
    Thomas DL: Hepatitis C and human immunodeficiency virus infection. Hepatology 2002, 36(Suppl 1):S201-S209.PubMedCrossRefGoogle Scholar
  65. 65.
    Aceti A, Pasquazzi C, Zechini B, De Bac C: Hepatotoxicity development during antiretroviral therapy containing protease inhibitors in patients with HIV: the role of hepatitis B and C virus infection. J Acquir Immune Defic Syndr 2002, 29:41–48.PubMedGoogle Scholar
  66. 66.
    Rimland D, Guest JL, Anderson KB: The effect of hepatitis C co-infection on survival in the Atlanta VA Cohort Study (HAVACS) in the post-HAART era. Paper presented at the 9th Conference on Retroviruses and Opportunistic Infections. Seattle, WA, February 24–28, 2002.Google Scholar
  67. 67.
    Braitstein P, Asselin JJ, Montessori V, et al.: The impact of the hepatitis C virus (HCV) on CD4 response post initiation of HAART among a population-based HIV treatment cohort. Presented at the 2nd International AIDS Society Conference on HIV Disease and Pathogenesis, abstract 214. Antivir Ther 2003, 8(Suppl 1):S235-S236.Google Scholar
  68. 68.
    Cowling BJ, Donnelly CA, Ghani AC, et al.: Virologic and immunologic response to antiretroviral therapy among HIV patients co-infected with hepatitis C virus (HCV)-analysis of a 6,401 HIV patient cohort [abstract B3300]. Paper presented at the XV International AIDS Conference. Bangkok, Thailand, July 11–16, 2004.Google Scholar
  69. 69.
    Dronda F, Zamora J, Moreno S, et al.: CD4 cell recovery during successful antiretroviral therapy in naive HIV-infected patients: the role of intravenous drug use. AIDS 2004, 18:2210–2212.PubMedCrossRefGoogle Scholar
  70. 70.
    Adinolfi LE, Andreana A, Utili R, et al.: HCV RNA levels in serum, liver, and peripheral blood mononuclear cells of chronic hepatitis C patients and their relationship to liver injury. Am J Gastroenterol 1998, 93:2162–2166.PubMedCrossRefGoogle Scholar
  71. 71.
    Penning M, Beld M, Goudsmit J: Peripheral blood mononuclear cells of HIV- and HCV-antibody-positive individuals contain HCV RNA but no HCV DNA despite evidence for reverse transcription of HIV RNA into DNA. Virology 2000, 268:12–16.PubMedCrossRefGoogle Scholar
  72. 72.
    Meier V, Mihm S, Braun Wietzke P, Ramadori G: HCV-RNA positivity in peripheral blood mononuclear cells of patients with chronic HCV infection: does it really mean viral replication? World J Gastroenterol 2001, 7:228–234.PubMedGoogle Scholar
  73. 73.
    Gong GZ, Lai LY, Jiang YF, et al.: HCV replication in PBMC and its influence on interferon therapy. World J Gastroenterol 2003, 9:291–294.PubMedGoogle Scholar
  74. 74.
    Valdez H, Anthony D, Farukhi F, et al.: Immune responses to hepatitis C and non-hepatitis C antigens in hepatitis C virus infected and HIV-1 coinfected patients. AIDS 2000, 14:2239–2246.PubMedCrossRefGoogle Scholar
  75. 75.
    De Luca A, Bugarini R, Lepri AC, et al.: Coinfection with hepatitis viruses and outcome of initial antiretroviral regimens in previously naive HIV-infected subjects. Arch Intern Med 2002, 162:2125–2132.PubMedCrossRefGoogle Scholar
  76. 76.
    Vigano A, Saresella M, Villa ML, et al.: CD38+CD8+ T cells as a marker of poor response to therapy in HIV-infected individuals. Chem Immunol 2000, 75:207–217.PubMedCrossRefGoogle Scholar
  77. 77.
    Taya N, Torimoto Y, Shindo M, et al.: Fas-mediated apoptosis of peripheral blood mononuclear cells in patients with hepatitis C. Br J Haematol 2000, 110:89–97.PubMedCrossRefGoogle Scholar
  78. 78.
    Treating opportunistic infections among HIV-infected adults and adolescents: Recommendations from CDC, the National Institutes of Health, and the HIV Medicine AssociationJInfectious Diseases Society of America. MMWR Morb Mortal Wkly Rep 2004, 53:50–53.Google Scholar
  79. 79.
    Thio CL, Nolt KR, Astemborski J, et al.: Screening for hepatitis C virus in human immunodeficiency virus-infected individuals. J Clin Microbiol 2000, 38:575–577.PubMedGoogle Scholar
  80. 80.
    Berggren RA, Jain R, Hester J,et al.: False-negative hepatitis C antibody is associated with low CD4 cell counts in HIVJHCV coinfected patients [abstract 562].Paper presented at the 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, February 4–8, 2001.Google Scholar
  81. 81.
    George SL, Gebhardt J, Klinzman D, et al.: Hepatitis C virus viremia in HIV-infected individuals with negative HCV antibody tests. J Acquir Immune Defic Syndr 2002, 31:154–162.PubMedGoogle Scholar
  82. 82.
    Dieterich DT: Hepatitis C virus and human immunodeficiency virus: clinical issues in coinfection. Am J Med 1999, 107:79S-84S.PubMedCrossRefGoogle Scholar
  83. 83.
    Villano SA, Vlahov D, Nelson KE, et al.: Persistence of viremia and the importance of long-term follow-up after acute hepatitis C infection. Hepatology 1999, 29:908–914.PubMedCrossRefGoogle Scholar
  84. 84.
    Child CG, Turcotte JG: Surgery and portal hypertension. In The Liver and Portal Hypertension. Edited by Child CG. Philadelphia: WB Saunders; 1964:50–64.Google Scholar
  85. 85.
    Poynard T, Bedossa P, Opolon P: Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 1997, 349:825–832.PubMedCrossRefGoogle Scholar
  86. 86.
    Pessione F, Degos F, Marcellin P, et al.: Effect of alcohol consumption on serum hepatitis C virus RNA and histological lesions in chronic hepatitis C. Hepatology 1998, 27:1717–1722.PubMedCrossRefGoogle Scholar
  87. 87.
    Kouvatsos P, Doerfler RE, Woodward WC: ALT does not predict hepatic fibrosis in HIVJHCV co-infected patients on antiretroviral therapy [abstract WePeB6040].Paper presented at the XIV International AIDS Conference. Barcelona, Spain, July 7–12, 2002.Google Scholar
  88. 88.
    Benhamou Y, Di Martino V, Bochet M, et al.: Factors affecting liver fibrosis in human immunodeficiency virus- and hepatitis C virus-coinfected patients: impact of protease inhibitor therapy. Hepatology 2001, 34:283–287.PubMedCrossRefGoogle Scholar
  89. 89.
    Poynard T, Ratziu V, Charlotte F, et al.: Rates and risk factors of liver fibrosis progression in patients with chronic hepatitis C. J Hepatol 2001, 34:730–739.PubMedCrossRefGoogle Scholar
  90. 90.
    Poles MA, Dieterich DT, Schwarz ED, et al.: Liver biopsy findings in 501 patients infected with human immunodeficiency virus (HIV). J Acquir Immune Defic Syndr Hum Retrovirol 1996, 11:170–177. This is a large study of liver biopsies in 501 HIV-infected patients, which demonstrated that this procedure is as safe in this population as in non-HIV-infected patients.PubMedGoogle Scholar
  91. 91.
    Quereda C, Moreno S, Moreno L, et al.: The role of liver biopsy in the management of chronic hepatitis C in patients infected with the human immunodeficiency virus. Hum Pathol 2004, 35:1083–1087.PubMedCrossRefGoogle Scholar
  92. 92.
    Soriano V, Puoti M, Sulkowski M, et al.: Care of patients with hepatitis C and HIV co-infection. AIDS 2004, 18:1–12.PubMedCrossRefGoogle Scholar
  93. 93.
    Fonquernie L, Serfaty L, Charrois A, et al.: Significance of hepatitis C virus coinfection with persistently normal alanine aminotransferase levels in HIV-1-infected patients. HIV Med 2004, 5:385–390.PubMedCrossRefGoogle Scholar
  94. 94.
    Marcellin P, Boyer N, Gervais A, et al.: Long-term histologic improvement and loss of detectable intrahepatic HCV RNA in patients with chronic hepatitis C and sustained response to interferon-alpha therapy. Ann Intern Med 1997, 127:875–881.PubMedGoogle Scholar
  95. 95.
    Soriano V, Garcia-Samaniego J, Bravo R, et al.: Interferon alpha for the treatment of chronic hepatitis C in patients infected with human immunodeficiency virus. Hepatitis-HIV Spanish Study Group. Clin Infect Dis 1996, 23:585–591.PubMedGoogle Scholar
  96. 96.
    Kostman JR, Smith J, Giffen CA, Frost KR: Interferon alfa-2b/ribavirin combination therapy in HCV/HIV co-infected persons: results of a multi-center, randomized, double-blind, placebo-controlled trial [abstract 634]. Hepatology 2001, 34:330A.CrossRefGoogle Scholar
  97. 97.
    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, 351:438–450. This is the original report of APRICOT, the largest randomized clinical trial to date of hepatitis C treatment. This study randomized 868 participants to receive PegIFN-α-2a plus ribavirin, regular IFN-α-2a plus ribavirin, or PegIFN-α-2a plus placebo, and established that PegIFN-α-2 plus ribavirin is the most effective treatment modality.PubMedCrossRefGoogle Scholar
  98. 98.
    Taylor LE, Rich JD, Tashima KT, et al.: Peginterferon plus ribavirin for hepatitis C in HIV-infected patients. N Engl J Med 2004, 351:2340–2342.PubMedCrossRefGoogle Scholar
  99. 99.
    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, 351:451–459. The ACTG Protocol 5071 compared conventional versus PegIFN-α-2a in 133 patients. Despite lower overall response rates than in other studies, it confirmed the greater effectiveness of the PegIFN-α-2 in a population with a larger proportion of patients with poor prognostic factors than in APRICOT.PubMedCrossRefGoogle Scholar
  100. 100.
    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, 292:2839–2848. The third large study of PegIFN-α versus conventional IFN published in 2004, RIBAVIC randomized 412 coinfected patients to PegIFN-α-2b or standard IFN-α-2b, both in combination with ribavirin. Findings were consistent with APRICOT and ACTG 5071, and highlighted the risk of the interaction between ribavirin and didanosine.PubMedCrossRefGoogle Scholar
  101. 101.
    McHutchison JG, Gordon SC, Schiff ER, et al.: Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med 1998, 339:1485–1492.PubMedCrossRefGoogle Scholar
  102. 102.
    Bressler BL, Guindi M, Tomlinson G, Heathcote J: High body mass index is an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C. Hepatology 2003, 38:639–644.PubMedCrossRefGoogle Scholar
  103. 103.
    Muir AJ, Bornstein JD, Killenberg PG: Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N Engl J Med 2004, 350:2265–2271.PubMedCrossRefGoogle Scholar
  104. 104.
    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, 140:346–355.PubMedGoogle Scholar
  105. 105.
    Shiffman ML, Di Bisceglie AM, Lindsay KL, et al.: Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment. Gastroenterology 2004, 126:1015–1023; discussion 947.PubMedCrossRefGoogle Scholar
  106. 106.
    Ishii K, Matsamaru K, Wakzui N, et al.: Early immune-mediated response to ribavirin combined with IFN in patients with chronic hepatitis C [ abstract 399 ].Paper presented at the 55th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, MA, October 29-November 2, 2004.Google Scholar
  107. 107.
    Crespo M, Esteban JI, Sauleda S, et al.: Early prediction of sustained virologic response (SVR) in patients with chronic hepatitis C (CHC) and HIV infection treated with IFN + RBV [abstract 428]. Paper presented at the 55th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, MA, October 29-November 2, 2004.Google Scholar
  108. 108.
    Moreno A, Garcia S, Moreno L: Negative prognostic value of HCV RNA decline at 4 weeks of treatment in both HCV-monoinfected and HCVJHIV-coinfected patients [abstract V-777].Paper presented at the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL, September 14–17, 2003.Google Scholar
  109. 109.
    Fattovich G, Giustina G, Favarato S, Ruol A: A survey of adverse events in 11,241 patients with chronic viral hepatitis treated with alfa interferon. J Hepatol 1996, 24:38–47.PubMedCrossRefGoogle Scholar
  110. 110.
    Dieperink E, Willenbring M, Ho SB: Neuropsychiatric symptoms associated with hepatitis C and interferon alpha: a review. Am J Psychiatry 2000, 157:867–876.PubMedCrossRefGoogle Scholar
  111. 111.
    Dieperink E, Ho SB, TetrickL, et al.: Suicidal ideation during interferon-alpha2b and ribavirin treatment of patients with chronic hepatitis C. Gen Hosp Psychiatry 2004, 26:237–240.PubMedCrossRefGoogle Scholar
  112. 112.
    Dieperink E, Ho SB, Thuras P, Willenbring ML: A prospective study of neuropsychiatric symptoms associated with interferon-alpha-2b and ribavirin therapy for patients with chronic hepatitis C. Psychosomatics 2003, 44:104–112.PubMedCrossRefGoogle Scholar
  113. 113.
    Levenson JL, Fallon HJ: Fluoxetine treatment of depression caused by interferon-alpha. Am J Gastroenterol 1993, 88:760–761.PubMedGoogle Scholar
  114. 114.
    Schramm TM, Lawford BR, Macdonald GA, Cooksley WG: Sertraline treatment of interferon-alfa-induced depressive disorder. Med J Aust 2000, 173:359–361.PubMedGoogle Scholar
  115. 115.
    Gleason OC, Yates WR: Five cases of interferon-alpha-induced depression treated with antidepressant therapy. Psychosomatics 1999, 40:510–512.PubMedGoogle Scholar
  116. 116.
    Landau A, Batisse D, Piketty C, et al.: Long-term efficacy of combination therapy with interferon-alpha 2b and ribavirin for severe chronic hepatitis C in HIV-infected patients. AIDS 2001, 15:2149–2155.PubMedCrossRefGoogle Scholar
  117. 117.
    Dieterich DT: Treatment of hepatitis C and anemia in human immunodeficiency virus-infected patients. J Infect Dis 2002, 185(Suppl 2):S128-S137.PubMedCrossRefGoogle Scholar
  118. 118.
    Baba M, Pauwels R, Balzarini J, et al.: Ribavirin antagonizes inhibitory effects of pyrimidine 2′,3′-dideoxynucleosides but enhances inhibitory effects of purine 2′,3′-dideoxynu-cleosides on replication of human immunodeficiency virus in vitro. Antimicrob Agents Chemother 1987, 31:1613–1617.PubMedGoogle Scholar
  119. 119.
    Hoggard PG, Kewn S, Barry MG, et al.: Effects of drugs on 2′,3′-dideoxy-2′,3′-didehydrothymidine phosphorylation in vitro. Antimicrob Agents Chemother 1997, 41:1231–1236.PubMedGoogle Scholar
  120. 120.
    Vogt MW, Hartshorn KL, Furman PA, et al.: Ribavirin antagonizes the effect of azidothymidine on HIV replication. Science 1987, 235:1376–1379.PubMedCrossRefGoogle Scholar
  121. 121.
    Blatt LM, Davis JM, Klein SB, Taylor MW: The biologic activity and molecular characterization of a novel synthetic interferon-alpha species, consensus interferon. J Interferon Cytokine Res 1996, 16:489–499.PubMedGoogle Scholar
  122. 122.
    Tong MJ, Reddy KR, Lee WM, et al.: Treatment of chronic hepatitis C with consensus interferon: a multicenter, randomized, controlled trial. Consensus Interferon Study Group. Hepatology 1997, 26:747–754.PubMedCrossRefGoogle Scholar
  123. 123.
    Osborn BL, Olsen HS, Nardelli B, et al.: Pharmacokinetic and pharmacodynamic studies of a human serum albumin-interferon-alpha fusion protein in cynomolgus monkeys. J Pharmacol Exp Ther 2002, 303:540–548.PubMedCrossRefGoogle Scholar
  124. 124.
    Sung C, Nardelli B, LaFleur DW, et al.: An IFN-beta-albumin fusion protein that displays improved pharmacokinetic and pharmacodynamic properties in nonhuman primates. J Interferon Cytokine Res 2003, 23:25–36.PubMedCrossRefGoogle Scholar
  125. 125.
    Pockros PJ, for the Pegasys/Levovirin Study Group: Combination of levovirin and peginterferon alfa-2a fails to generate virological response comparable to ribavirin-peginterferon alfa-2a combination therapy in patients with chronic HCV [abstract 525]. Paper presented at the 55th Annual Meeting of The American Association for the Study of Liver Diseases. Boston, MA, October 29-November 2, 2004.Google Scholar
  126. 126.
    Gish RG, Arora S, Nelson D: Safety and efficacy of viramidine in combination with pegylated interferon alfa-2a for treatment of hepatitis C in therapy-naive patients [abstract 479/762]. Paper presented at the 39th Annual Meeting of The European Association for the Study of the Liver. Berlin, Germany, April 14–18, 2004.Google Scholar
  127. 127.
    Hinrichsen H, Benhamou Y, Wedemeyer H, et al.: Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype 1 patients. Gastroenterology 2004, 127:1347–1355.PubMedCrossRefGoogle Scholar
  128. 128.
    Duclow-Vallee JD, Vittecoq D, Teicher E: Experience of liver transplantation (LT) in 20 HIV-HCV co-infected patients in the highly active antiretroviral (HAART) era 2000–2004 [abstract 69]. Paper presented at the 55th Annual Meeting of The American Association for the Study of Liver Diseases. Boston, MA, October 29-November 2, 2004.Google Scholar
  129. 129.
    Fung J, Eghtesad B, Patel-Tom K, et al.: Liver transplantation in patients with HIV infection. Liver Transpl 2004, 10(Suppl2):S39-S53.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2005

Authors and Affiliations

  • Benigno Rodriguez
    • 1
  • David A. Bobak
  1. 1.Division of Infectious DiseasesUniversity Hospitals of ClevelandClevelandUSA

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