Download PDF
Semin Liver Dis 2003; 23(2): 149-166
DOI: 10.1055/s-2003-39946
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Hepatitis C Virus in Human Immunodeficiency Virus-Infected Individuals: An Emerging Comorbidity with Significant Implications

Stevan A. Gonzalez1 , Andrew H. Talal2
  • 1Center for the Study of Hepatitis C and Department of Medicine, Weill Medical College of Cornell University, New York, New York
  • 2Assistant Professor of Medicine, Center for the Study of Hepatitis C and Department of Medicine, Weill Medical College of Cornell University, New York, New York
Further Information

Publication History

Publication Date:
11 June 2003 (online)

    Permissions and Reprints

ABSTRACT

As antiretroviral (ARV) therapy has become more effective, hepatitis C virus (HCV) infection has emerged as an important cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals. HIV alters HCV clinical presentation, epidemiology, virology, and pathogenesis compared with HCV monoinfected individuals. The incidence of chronic and vertical HCV infection is increased, the rate of hepatic fibrosis progression is accelerated, peripheral and intrahepatic HCV RNA levels are increased, and end-stage liver disease (ESLD) and cirrhosis develop more rapidly in coinfected individuals. Based on these observations, combined with the increased efficacy of ARV therapy, several societies have recommended the diagnosis and treatment of HCV in coinfected individuals. HCV treatment with nonspecific antivirals, pegylated interferon alpha (PEG-IFN) and ribavirin (RBV), is more complex in coinfected individuals compared with monoinfected individuals because these regimens appear to have decreased efficacy and the incidence of complications is increased. Although new HCV-specific regimens show early promise in HCV monoinfected individuals, it is likely that these agents will be used in combination with nonspecific therapies and additional studies will be required to evaluate their efficacy in coinfected individuals.

KEYWORDS

Hepatitis C virus - human immunodeficiency virus - coinfection

REFERENCES

  • 1 Alter M J, Kruszon-Moran D, Nainan O V. et al . The prevalence of hepatitis C virus infection in the United States, 1988 through 1994.  N Engl J Med . 1999;  351 556-562
    PubMedGoogle Scholar
  • 2 Centers for Disease Control and Prevention, Office of Communication. Facts about hepatitis C [on-line] Available: www.cdc.gov/od/oc/media/fact/hepcqa.htm; October 1998; accessed November 29 2002
  • 3 Centers for Disease Control and Prevention. HIV/AIDS update: a glance at the HIV epidemic [on-line] Available: www.cdc.gov/hiv/pubs/facts.htm; accessed November 29 2002
  • 4 Sulkowski M S, Mast E E, Seeff L B, Thomas D L. Hepatitis C virus infection as an opportunistic disease in persons infected with human immunodeficiency virus.  Clin Infect Dis . 2000;  30 S77-84
    CrossrefPubMedGoogle Scholar
  • 5 Staples C T, Rimland D, Dudas D. Hepatitis C in the HIV (human immunodeficiency virus) Atlanta VA (Veterans Affairs Medical Center) Cohort Study (HAVACS): the effect of co-infection on survival.  Clin Infect Dis . 1999;  29 150-154
    PubMedGoogle Scholar
  • 6 Palella F J, Delaney K M, Moorman A C. et al . Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection.  N Engl J Med . 1998;  338 853-860
    CrossrefPubMedGoogle Scholar
  • 7 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
    PubMedGoogle Scholar
  • 8 Eyster M E, Fried M W, Di Bisceglie M A, Goedert J J. 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
  • 9 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
    CrossrefPubMedGoogle Scholar
  • 10 Puoti M, Bonacini M, Spinetti A. et al . Liver fibrosis progression is related to CD4 cell depletion in patients co-infected with hepatitis C virus and human immunodeficiency virus.  J Infect Dis . 2001;  183 134-137
    CrossrefPubMedGoogle Scholar
  • 11 Pol S, Fontaine H, Carnot F. et al . Predictive factors for development of cirrhosis in parenterally acquired chronic hepatitis C: a comparison between immunocompetent and immunocompromised patients.  J Hepatol . 1998;  29 12-19
    CrossrefPubMedGoogle Scholar
  • 12 Benhamou Y, Bochet M, Di Martino V. et al . Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus co-infected patients.  Hepatology . 1999;  30 1054-1058
    CrossrefPubMedGoogle Scholar
  • 13 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 co-infection.  Lancet . 2000;  356 1800-1805
    CrossrefPubMedGoogle Scholar
  • 14 De Luca A, Bugarini R, Lepri A C. 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
    CrossrefPubMedGoogle Scholar
  • 15 Sulkowski M S, Moore R D, Mehta S H, Chaisson R E, Thomas D L. Hepatitis C and progression of HIV disease.  JAMA . 2002;  288 199-206
    CrossrefPubMedGoogle Scholar
  • 16 Rossi S J, Volberding P A, Wright T L. Does hepatitis C virus infection increase the risk of HIV disease progression?.  JAMA . 2002;  288 241-243
    CrossrefPubMedGoogle Scholar
  • 17 Sulkowski M S, Thomas D L, Chaisson R E, Moore R D. 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
    CrossrefPubMedGoogle Scholar
  • 18 Cooper C L, Parbhakar M A, Angel J B. Hepatotoxicity associated with antiretroviral therapy containing dual versus single protease inhibitors in individuals coinfected with hepatitis C virus and human immunodeficiency virus.  Clin Infect Dis . 2002;  34 1259-1263
    CrossrefPubMedGoogle Scholar
  • 19 Benhamou Y, Di Martino V, Bochet M. et al . Factors affecting liver fibrosis in human immunodeficiency virus- and hepatitis C virus-co-infected patients: impact of protease inhibitor therapy.  Hepatology . 2001;  34 283-287
    CrossrefPubMedGoogle Scholar
  • 20 Memon M I, Memon M A. Hepatitis C: an epidemiological review.  J Viral Hepat . 2002;  9 84-100
    CrossrefPubMedGoogle Scholar
  • 21 World Health Organization. Hepatitis C. Fact Sheet No. 164 [on-line] Revised October 2000. Available: www.who.int/inf-fs/en/fact164.html; accessed November 25 2002
  • 22 Freeman A J, Marinos G, French R A, Lloyd A R. Immunopathogenesis of hepatitis C virus infection.  Immunol Cell Biol . 2001;  79 515-536
    CrossrefPubMedGoogle Scholar
  • 23 Zein N N, Rakela J, Krawitt E L. et al . Hepatitis C virus genotypes in the United States: epidemiology, pathogenicity, and response to interferon therapy.  Ann Intern Med . 1996;  125 634-639
    PubMedGoogle Scholar
  • 24 Bruno S, Silini E, Crosignani A. et al . Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: a prospective study.  Hepatology . 1997;  25 754-758
    CrossrefPubMedGoogle Scholar
  • 25 Nousbaum J, Pol S, Nalpas B. et al . Hepatitis C virus type 1b (II) infection in France and Italy.  Ann Intern Med . 1995;  122 161-168
    PubMedGoogle Scholar
  • 26 Zein N N, Poterucha J J, Gross J B. et al . Increased risk of hepatocellular carcinoma in patients infected with hepatitis C genotype 1b.  Am J Gastroenterol . 1996;  91 2560-2562
    PubMedGoogle Scholar
  • 27 Serfaty L, Chazouilleres O, Poujol-Robert A. et al . Risk factors for cirrhosis in patients with chronic hepatitis C virus infection: results of a case-control study.  Hepatology . 1997;  26 776-779
    PubMedGoogle Scholar
  • 28 Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C.  Lancet . 1997;  349 825-832
    CrossrefPubMedGoogle Scholar
  • 29 Rubbia-Brandt L, Leandro G, Spahr L. et al . Liver steatosis in chronic hepatitis C: a morphological sign suggesting infection with HCV genotype 3.  Histopathology . 2001;  39 119-124
    CrossrefPubMedGoogle Scholar
  • 30 Westin J, Nordlinder H, Lagging M, Norkrans G, Wejstal R. Steatosis accelerates fibrosis development over time in hepatitis C virus genotype 3 infected patients.  J Hepatol . 2002;  37 837-842
    CrossrefPubMedGoogle Scholar
  • 31 World Health Organization. Report on the global HIV/AIDS epidemic 2002 [on-line] Available: www.who.int/hiv/pub/ epidemiology/pubepidemic2002/en/; accessed November 29 2002
  • 32 Quiñones-Mateu M E, Gao Y, Ball S C. et al . In vitro intersubtype recombinants of human immunodeficiency virus type 1: comparison to recent and circulating in vivo recombinant forms.  J Virol . 2002;  76 9600-9613
    CrossrefPubMedGoogle Scholar
  • 33 Reeves J D, Doms R W. Human immunodeficiency virus type 2.  J Gen Virol . 2002;  83 1253-1265
    PubMedGoogle Scholar
  • 34 Miller C L, Johnston C, Spittal P M. et al . Opportunities for prevention: hepatitis C prevalence and incidence in a cohort of young injection drug users.  Hepatology . 2002;  36 737-742
    CrossrefPubMedGoogle Scholar
  • 35 Centers for Disease Control, National Center for Infectious Diseases. Viral hepatitis C fact sheet [on-line] Available: www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm; accessed on November 29 2002
  • 36 Rockstroh J K, Spengler U, Sudhop T. et al . Immunosuppression may lead to progression of hepatitis C virus-associated liver disease in hemophiliacs co-infected with HIV.  Am J Gastroenterol . 1996;  91 2563-2568
    PubMedGoogle Scholar
  • 37 Pol S, Vallet-Pichard A, Fontaine H, Lebray P. HCV infection and hemodialysis.  Semin Nephrol . 2002;  22 331-339
    PubMedGoogle Scholar
  • 38 Hisada M, O'Brien T R, Rosenberg P S, Goedert J J. Virus load and risk of heterosexual transmission of human immunodeficiency virus and hepatitis C virus by men with hemophilia.  J Infect Dis . 2000;  181 1475-1478
    CrossrefPubMedGoogle Scholar
  • 39 Eyster M C, Alter H J, Aledort L M. et al . Heterosexual co-transmission of hepatitis C virus and human immunodeficiency virus.  Ann Intern Med . 1991;  115 764-768
    PubMedGoogle Scholar
  • 40 Soto B, Rodrigo L, Garcia-Bengoechea M. et al . Heterosexual transmission of hepatitis C virus and the possible role of coexistent human immunodeficiency infection in the index case: A Multicentre Study of 423 Pairings.  J Intern Med . 1994;  236 515-519
    PubMedGoogle Scholar
  • 41 Yeung L TF, King S M, Roberts E A. Mother-to-infant transmission of hepatitis C virus.  Hepatology . 2001;  34 223-229
    CrossrefPubMedGoogle Scholar
  • 42 Thomas D L, Villano S A, Riester K A. et al . Perinatal transmission of hepatitis C virus from human immunodeficiency virus type 1-infected mothers.  J Infect Dis . 1998;  177 1480-1488
    PubMedGoogle Scholar
  • 43 Quinn T C, Wawer M J, Sewankambo N. et al . Viral load and heterosexual transmission of human immunodeficiency virus type 1.  N Engl J Med . 2000;  342 921-929
    CrossrefPubMedGoogle Scholar
  • 44 Patchen L, Khoshnood K. Risk of perinatal transmission with treatment combinations of intrapartum and newborn zidovudine monotherapy.  AIDS Read . 2001;  11 269-277
    PubMedGoogle Scholar
  • 45 Guay L A, Musoke P, Fleming T. et al . Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-infant transmission of HIV-1 in Kampala, Uganda: HIVNET-012 randomised trial.  Lancet . 1999;  354 795-802
    PubMedGoogle Scholar
  • 46 Hiratsuka M, Minakami H, Koshizuka S, Sato I. Administration of interferon-α during pregnancy: effect on fetus.  J Perinat Med . 2000;  28 372-376
    CrossrefPubMedGoogle Scholar
  • 47 Koretz R L, Brezina M, Polito A J. et al . Non-A, non-B posttransfusion hepatitis: comparing C and non-C hepatitis.  Hepatology . 1993;  17 361-365
    CrossrefPubMedGoogle Scholar
  • 48 Thimme R, Oldach D, Chang K. et al . determinants of viral clearance and persistence during acute hepatitis C virus infection.  J Exp Med . 2001;  194 1395-1406
    CrossrefPubMedGoogle Scholar
  • 49 Schacker T, Collier A C, Hughes J, Shea T, Corey L. Clinical and epidemiologic features of primary HIV infection.  Ann Intern Med . 1996;  125 257-264
    CrossrefPubMedGoogle Scholar
  • 50 Seeff L B, Hollinger F B, Alter H J. et al . Long-term mortality and morbidity of transfusion-associated non-A, non-B and type C hepatitis: A National Heart, Lung, and Blood Institute Collaborative Study.  Hepatology . 2001;  33 455-463
    CrossrefPubMedGoogle Scholar
  • 51 Kenny-Walsh E. Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin.  N Engl J Med . 1999;  340 1228-1233
    CrossrefPubMedGoogle Scholar
  • 52 Wiese M, Berr F, Lafrenz M, Porst H, Oesen U. Low frequency of cirrhosis in a hepatitis C (genotype 1b) single-source outbreak in Germany: a 20-year multicenter study.  Hepatology . 2000;  32 91-96
    CrossrefPubMedGoogle Scholar
  • 53 Centers for Disease Control and Prevention. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic liver disease.  MMWR Morb Mortal Wkly Rep . 1998;  47 1-39
    PubMedGoogle Scholar
  • 54 Mehta S, Levey J M, Bonkovsky H L. Extrahepatic manifestations of infection with hepatitis C virus.  Clin Liver Dis . 2001;  5 979-1008
    PubMedGoogle Scholar
  • 55 Pugh R NH, Murray-Lyon I M, Dawson J L, Peitroni M C, Williams R. Transection of the oesophagus for bleeding oesophageal varices.  Br J Surg . 1973;  60 646-648
    CrossrefPubMedGoogle Scholar
  • 56 Malinchoc M, Kamath P S, Gordon F D. et al . A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts.  Hepatology . 2000;  31 864-871
    CrossrefPubMedGoogle Scholar
  • 57 Brown R S, Kumar K S, Russo M W. et al . Model for end-stage liver disease and Child-Turcotte-Pugh score as predictors of pretransplantation disease severity, posttransplantation outcome, and resource utilization in United Network for Organ Sharing Status 2A Patients.  Liver Transplant . 2002;  8 278-284
    CrossrefPubMedGoogle Scholar
  • 58 Kamath P S, Wiesner R H, Malinchoc M. et al . A model to predict survival in patients with end-stage liver disease.  Hepatology . 2001;  33 464-470
    CrossrefPubMedGoogle Scholar
  • 59 Pagliaro L. MELD: the end of Child-Pugh classification?.  J Hepatol . 2002;  36 141-142
    PubMedGoogle Scholar
  • 60 Kato Y, Nakata K, Omagari K. et al . Risk of hepatocellular carcinoma in patients with cirrhosis in Japan. Analysis of infectious hepatitis viruses.  Cancer . 1994;  74 2234-2238
    PubMedGoogle Scholar
  • 61 Di Bisceglie M A. Hepatitis C and hepatocellular carcinoma.  Hepatology . 1997;  26 34S-38S
    CrossrefPubMedGoogle Scholar
  • 62 Yoshida H, Shiratori Y, Moriyama M. et al . Interferon therapy reduces the risk for hepatocelluar carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan.  Ann Intern Med . 1999;  131 174-181
    PubMedGoogle Scholar
  • 63 El-Serag H B. Hepatocellular carcinoma: an epidemiologic view.  J Clin Gastroenterol . 2002;  35 S72-S78
    CrossrefPubMedGoogle Scholar
  • 64 Ishikawa T, Ichida T, Yamagiwa S. et al . High viral loads, serum alanine aminotransferase and gender are predictive factors for the development of hepatocellular carcinoma from viral compensated liver cirrhosis.  J Gastroenterol Hepatol . 2001;  16 1274-1281
    CrossrefPubMedGoogle Scholar
  • 65 Roudot-Thoraval F, Bastie A, Pawlotsky J, Dhumeaux D. Epidemiological factors affecting the severity of hepatitis C virus-related liver disease: a French survey of 6,664 patients.  Hepatology . 1997;  26 485-490
    CrossrefPubMedGoogle Scholar
  • 66 Bruno R, Sacchi P, Filice C, Puoti M, Filice G. Hepatocellular carcinoma in HIV-infected patients with chronic hepatitis: an emerging issue.  J Acquir Immune Defic Syndr . 2002;  30 535-536
    PubMedGoogle Scholar
  • 67 Izumi N, Asahina Y, Noguchi O. et al . Risk factors for distant recurrence of hepatocellular caricinoma in the liver after complete coagulation by microwave or radiofrequency ablation.  Cancer . 2001;  91 949-956
    CrossrefPubMedGoogle Scholar
  • 68 Hanazaki K, Wakabayashi M, Sodeyama H. et al . Surgical outcome in cirrhotic patients with hepatitis C-related hepatocellular carcinoma.  Hepatogastroenterology . 2000;  47 204-210
    PubMedGoogle Scholar
  • 69 Weber J. The pathogenesis of HIV-1 infection.  Br Med Bull . 2001;  58 61-72
    PubMedGoogle Scholar
  • 70 Phair J, Munoz A, Detels R. et al . The risk of Pneumocystis carinii pneumonia among men with human immunodeficiency virus type 1.  N Engl J Med . 1990;  322 161-165
    CrossrefPubMedGoogle Scholar
  • 71 Sepkowitz K A. Opportunistic infections in patients with and patients without acquired immunodeficiency syndrome.  Clin Infect Dis . 2002;  34 1098-1107
    CrossrefPubMedGoogle Scholar
  • 72 Moylett E H, Shearer W T. HIV: clinical manifestations.  J Allergy Clin Immunol . 2002;  110 3-16
    CrossrefPubMedGoogle Scholar
  • 73 Telfer P, Sabin C, Devereux H. et al . The progression of HCV-associated liver disease in a cohort of haemophilic patients.  Br J Haematol . 1994;  87 555-561
    CrossrefPubMedGoogle Scholar
  • 74 Thimme R, Bukh J, Spangenberg H C. et al . Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease.  Proc Natl Acad Sci USA . 2002;  99 15661-15668
    CrossrefPubMedGoogle Scholar
  • 75 Ramratnam B, Bonhoeffer S, Binley J. et al . Rapid production and clearance of HIV-1 and hepatitis C virus assessed by large volume plasma apheresis.  Lancet . 1999;  354 1782-1785
    CrossrefPubMedGoogle Scholar
  • 76 Neumann A U, Lam N P, Dahari H. et al . Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-α therapy.  Science . 1998;  282 103-107
    CrossrefPubMedGoogle Scholar
  • 77 Neumann A U, Lam N P, Dahari H. et al . Differences in viral dynamics between genotypes 1 and 2 of hepatitis C virus.  J Infect Dis . 2000;  182 28-35
    CrossrefPubMedGoogle Scholar
  • 78 Little S J, McLean A R, Spina C A, Richman D D, Havlir D V. Viral dynamics of acute HIV-1 infection.  J Exp Med . 1999;  190 841-850
    CrossrefPubMedGoogle Scholar
  • 79 Ho D D, Neumann A U, Perelson A S. et al . Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection.  Nature . 1995;  373 123-126
    CrossrefPubMedGoogle Scholar
  • 80 Appay V, Papagno L, Spina C. et al . Dynamics of T cell responses in HIV infection.  J Immunol . 2002;  168 3660-3666
    PubMedGoogle Scholar
  • 81 Wei X, Ghosh S K, Taylor M E. et al . Viral dynamics in human immunodeficiency virus type 1 infection.  Nature . 1995;  373 117-122
    CrossrefPubMedGoogle Scholar
  • 82 Torriani F J, Ribeiro R M, Gilbert T L. et al .Early HCV viral dynamics in HIV/HCV-infected patients on HCV treatment. Presented at the Ninth Conference on Retroviruses and Opportunistic Infections. February 24-28, 2002; Seattle, WA. Abstract 121
    Google Scholar
  • 83 Sherman K E, Horn P, Rouster S. et al .HCV RNA kinetic response to PEG-interferon and ribavirin in HIV co-infected patients. Presented at the Ninth Conference on Retroviruses and Opportunistic Infections. February 24, 2002; Seattle, WA. Abstract 122
    Google Scholar
  • 84 Talal A H, Shata M T, Flynn S M. et al .HCV dynamics in HIV/HCV co-infected patients treated with pegylated interferon and ribavirin. Presented at the 53rd Annual Meeting of AASLD. November 2-5, 2002; Boston, MA. Abstract 154
    Google Scholar
  • 85 Talal A H, Flynn S M, Dorante G. et al .Hepatitis C virus dynamics HIV/HCV co-infection in response to daily, high-dose interferon-α-2a. Presented at the 52nd Annual Meeting of AASLD. November 9-13, 2001; Dallas, TX. Abstract 1529
    Google Scholar
  • 86 Mehal W Z, Azzaroli F, Crispe I N. Immunology of the healthy liver: old questions and new insights.  Gastroenterology . 2001;  120 250-260
    PubMedGoogle Scholar
  • 87 Bertolino P, Trescol-Biemont M C, Rabourdin-Combe C. Hepatocytes induce functional activation of naïve CD8+ T lymphocytes but fail to promote survival.  Eur J Immunol . 1998;  28 221-236
    CrossrefPubMedGoogle Scholar
  • 88 Maher J J. Interactions between hepatic stellate cells and the immune system.  Semin Liver Dis . 2001;  21 417-426
    Article in Thieme ConnectPubMedGoogle Scholar
  • 89 Nuovo G J, Holly A, Wakely P, Frankel W. Correlation of histology, viral load, and in situ viral detection in hepatic biopsies from patients with liver transplants secondary to hepatitis C infection.  Hum Pathol . 2002;  33 277-284
    CrossrefPubMedGoogle Scholar
  • 90 Garson J A, Tuke P W, Makris M. et al . Demonstration of viraemia patterns in haemophiliacs treated with hepatitis-C-virus-contaminated factor VIII concentrates.  Lancet . 1990;  336 1022-1025
    CrossrefPubMedGoogle Scholar
  • 91 Tremolada F, Casarin C, Tagger A. et al . Antibody to hepatitis C virus in post-transfusion hepatitis.  Ann Intern Med . 1991;  114 277-281
    PubMedGoogle Scholar
  • 92 Cramp M E, Rossol S, Chokshi S. et al . Hepatitis C virus-specific T-cell reactivity during interferon and ribavirin treatment in chronic hepatitis C.  Gastroenterology . 2000;  118 346-355
    PubMedGoogle Scholar
  • 93 Grüner N H, Gerlach T J, Jung M. et al . Association of hepatitis C virus-specific CD8+ T cells with viral clearance in acute hepatitis C.  J Infect Dis . 2000;  181 1528-1536
    CrossrefPubMedGoogle Scholar
  • 94 Brown P MJ, Neuman M G. Immunopathogenesis of hepatitis C viral infection: TH1/TH2 responses and the role of cytokines.  Clin Biochem . 2001;  34 167-171
    PubMedGoogle Scholar
  • 95 Abbas A K, Murphy K M, Sher A. Functional diversity of helper T lymphocytes.  Nature . 1999;  383 787-793
    PubMedGoogle Scholar
  • 96 Iredale J P. Hepatic stellate cell behavior during resolution of liver injury.  Semin Liver Dis . 2001;  21 427-435
    Article in Thieme ConnectPubMedGoogle Scholar
  • 97 Canchis P W, Davila J, Fiel M I. et al .Characterization of intrahepatic lymphocytes and hepatocytes in HIV/HCV coinfected and HCV mono-infected individuals. Presented at the Ninth International Meeting on Hepatitis C Virus and Related Viruses. July 7-11, 2002; San Diego, CA
    Google Scholar
  • 98 Dragic T. An overview of the determinants of CCR5 and CXCR4 co-receptor function.  J Gen Virol . 2001;  82 1807-1814
    PubMedGoogle Scholar
  • 99 Clark S J, Saag M S, Decker W D. et al . High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection.  N Engl J Med . 1991;  324 954-960
    PubMedGoogle Scholar
  • 100 Mellors J W, Rinaldo C R, Gupta P. et al . Prognosis in HIV-1 infection predicted by the quantity of virus in plasma.  Science . 1996;  272 1167-1170
    PubMedGoogle Scholar
  • 101 Mohri H, Perelson A S, Tung K. et al . Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy.  J Exp Med . 2001;  194 1277-1287
    CrossrefPubMedGoogle Scholar
  • 102 Badley A D, Pilon A A, Landay A, Lynch D H. Mechanisms of HIV-associated lymphocyte apoptosis.  Blood . 2000;  96 2951-2964
    PubMedGoogle Scholar
  • 103 McHutchison J G, Shad J A, Gordon S C. et al . Predicting response to initial therapy with interferon plus ribavirin in chronic hepatitis C using serum HCV RNA results during therapy.  J Viral Hepat . 2001;  8 414-420
    CrossrefPubMedGoogle Scholar
  • 104 Housset C, Lamas E, Courgnaud V. et al . Presence of HIV-1 in human parenchymal and non-parenchymal liver cells in vivo.  J Hepatol . 1993;  19 252-258
    CrossrefPubMedGoogle Scholar
  • 105 Cao Y Z, Dieterich D, Thomas P A. et al . Identification and quantitation of HIV-1 in the liver of patients with AIDS.  AIDS . 1992;  6 65-70
    PubMedGoogle Scholar
  • 106 Hufert F T, Schmitz J, Schreiber M. et al . Human Kupffer cells infected with HIV-1 in vivo.  J Acquir Immune Defic Syndr . 1993;  6 772-777
    PubMedGoogle Scholar
  • 107 Kaplan J E, Masur H, Holmes K K. Guidelines for preventing opportunistic infections among HIV infected persons.  MMWR Morb Mortal Wkly Rep . 2002;  51 1-46
    PubMedGoogle Scholar
  • 108 Thomas D L, Astemborski J, Rai R M. et al . The natural history of hepatitis C virus infection: host, viral, and environmental factors.  JAMA . 2000;  284 450-456
    CrossrefPubMedGoogle Scholar
  • 109 Talal A H. Hepatitis C virus in people with HIV infection.  Lancet . 2002;  360 2088-2089
    PubMedGoogle Scholar
  • 110 National Institutes of Health Consensus Development Conference Statement. Management of hepatitis C: 2002 [on-line]. June 10-12, 2002, revisions September 12, 2002;19:1 Available: consensus.nih.gov/cons/116/091202116cdc statement.htm; accessed November 29 2002
  • 111 Takaki A, Wiese M, Maertens G. et al . Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source outbreak of hepatitis C.  Nat Med . 2000;  6 578-582
    PubMedGoogle Scholar
  • 112 Thio C L, Nolt K R, Astemborski J. et al . Screening for hepatitis C virus in human immunodeficiency virus-infected individuals.  J Clin Microbiol . 2000;  38 575-577
    PubMedGoogle Scholar
  • 113 Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C.  Hepatology . 1996;  24 289-293
    CrossrefPubMedGoogle Scholar
  • 114 The METAVIR Cooperative Study Group. Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C.  Hepatology . 1994;  20 15-20
    CrossrefPubMedGoogle Scholar
  • 115 McHutchison J G, Davis G L, Esteban-Mur R. et al .Durability of sustained virologic response in patients with chronic hepatitis C after treatment with interferon α-2b alone or in combination with ribavirin. Presented at the 52nd Annual Meeting of AASLD. November 9-13, 2001; Dallas, TX. Abstract 281
    Google Scholar
  • 116 Manns M P, McHutchison J G, Gordon S C. 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;  358 958-965
    CrossrefPubMedGoogle Scholar
  • 117 Fried M W, Shiffman M L, Reddy K R. et al . Pegterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection.  N Engl J Med . 2002;  347 975-982
    CrossrefPubMedGoogle Scholar
  • 118 Jaeckel E, Cornberg M, Wedemeyer H. et al . Treatment of acute hepatitis C with interferon alfa-2b.  N Engl J Med . 2001;  345 1452-1457
    CrossrefPubMedGoogle Scholar
  • 119 Bini E J, Reid M, Mannix R A, Wu B. Safety and efficacy of interferon alfa-2b and ribavirin combination therapy for the treatment of hepatitis C in patients coinfected with HIV. Presented at the 52nd Annual Meeting of AASLD. November 9-13, 2001; Dallas, TX. Abstract 653
    Google Scholar
  • 120 Puoti M, Barbara Z, Paolo Q. et al .Human immune deficiency virus (HIV) co-infection impairs responsiveness to interferon (IFN) and ribavirin (RBV) combination in patients with chronic hepatitis C: preliminary results of a comparative study. Presented at the 53rd Annual Meeting of AASLD. November 2-5, 2002; Boston, MA. Abstract 506
    Google Scholar
  • 121 Zylberberg H, Benhamou Y, Lagneaux J L. et al . Safety and efficacy of interferon-ribavirin combination therapy in HCV-HIV co-infected subjects: an early report.  Gut . 2000;  47 694-697
    CrossrefPubMedGoogle Scholar
  • 122 Nasti G, Di Gennaro G, Tavio M. et al . Chronic hepatitis C in HIV infection: feasibility and sustained efficacy of therapy with interferon alpha-2b and ribavirin.  AIDS . 2001;  15 1783-1787
    CrossrefPubMedGoogle Scholar
  • 123 Landau A, Batisse D, Piketty C. et al . Long-term efficacy of combination therapy with interferon-a2b and ribavirin for severe chronic hepatitis C in HIV-infected patients.  AIDS . 2001;  15 2149-2155
    CrossrefPubMedGoogle Scholar
  • 124 Sauleda S, Juarez A, Esteban J I. et al . Interferon and ribavirin combination therapy for chronic hepatitis C in human immunodeficiency virus-infected patients with congenital coagulation disorders.  Hepatology . 2001;  34 1035-1040
    CrossrefPubMedGoogle Scholar
  • 125 Kostman J R, Smith J J, Giffen C A, Frost K R. Interferon α-2b/ribavirin combination therapy in HIV/HCV co-infected persons: results of a multicenter randomized, double-blind, controlled trial (American Foundation for AIDS Research Study). Presented at the 52nd Annual Meeting of AASLD. November 9-13, 2001; Dallas, TX. Abstract 634
    Google Scholar
  • 126 Khalili M, Hoffman-Terry M, Hassahein T I. et al .Safety and efficacy of 40 kDa peginterferon alfa-2a (Pegasys) in the treatment of patients co-infected with HIV and HCV: preliminary results from a randomized, multicenter trial. Presented at the 52nd Annual Meeting of AASLD. November 9-13, 2001; Dallas, TX. Abstract 623
    Google Scholar
  • 127 Hopkins S, Hennessy M, Lyons F, Mulachy F, Bergin C. Treatment of chronic hepatitis c with pegylated interferon and ribavirin in HIV co-infected patients. Presented at the 53rd Annual Meeting of AASLD. November 2-5, 2002; Boston, MA. Abstract 258
    Google Scholar
  • 128 Myers R P, Benhamou Y, Bochet M. et al .Pegylated interferon alfa-2b and ribavirin in HIV/HCV-coinfected patients. Presented at the 53rd Annual Meeting of AASLD. November 2-5, 2002; Boston, MA. Abstract 1649
    Google Scholar
  • 129 Perronne C, Carrat F, Banisadr F. et al .ANRS HC02- RIBAVIC: a randomized controlled trial of pegylated-interferon alfa-2b plus ribavirin vs. interferon alpha-2b plus ribavirin for the initial treatment of chronic hepatitis C in HIV Co-Infected Patients. Presented at the 42nd ICAAC. September 27-30, 2002; San Diego, CA. Abstract H-1083
    Google Scholar
  • 130 Chung R, Anderson J, Alston B. et al .A randomized, controlled trial of pegylated interferon alpha-2a with ribavirin vs. interferon alpha-2a with ribavirin for the treatment of chronic HCV in HIV co-infection. ACTG A5071. Presented at the Ninth Conference on Retroviruses and Opportunistic Infections. February 24, 2002; Seattle, WA. Abstract LB-15
    Google Scholar
  • 131 Bekkering F C, Stalgis C, McHutchison J G, Brouwer J T, Perelson A S. Estimation of early hepatitis C viral clearance in patients receiving daily interferon and ribavirin therapy using a mathematical model.  Hepatology . 2001;  33 419-423
    CrossrefPubMedGoogle Scholar
  • 132 Lam N P, Neumann A U, Gretch D R. et al . Dose-dependent acute clearance of hepatitis C genotype 1 virus with interferon alfa.  Hepatology . 1997;  26 226-231
    PubMedGoogle Scholar
  • 133 Buti M, Sanchez-Avila F, Lurie Y. et al . Viral kinetics in genotype 1 chronic hepatitis C patients during therapy with 2 different doses of peginterferon alfa-2b plus ribavirin.  Hepatology . 2002;  35 930-936
    CrossrefPubMedGoogle Scholar
  • 134 Bekkering F C, Brouwer J T, Schalm S W, Elewaut A. Hepatitis C: viral kinetics.  Hepatology . 1997;  26 1691-1693
    PubMedGoogle Scholar
  • 135 Pesce A, Taillan B, Rosenthal E. et al . Opportunistic infections and CD4 lymphocytopenia with interferon treatment in HIV-1 infected patients.  Lancet . 1993;  341 1597
    CrossrefPubMedGoogle Scholar
  • 136 Talal A H. Opportunistic infections in HIV-infected individuals: hepatitis C virus.  Lancet . 2002;  360 584-586
    PubMedGoogle Scholar
  • 137 Fontaine H, Pol S. Side effects of interferon-α in treating hepatitis C virus infection.  Transplant Proc . 2001;  33 2327-2329
    CrossrefPubMedGoogle Scholar
  • 138 Dieterich D T. Treatment of hepatitis C and anemia in human immunodeficiency virus-infected patients.  J Infect Dis . 2002;  185 S128-S137
    PubMedGoogle Scholar
  • 139 Hinrichsen et al. First report on the antiviral efficacy of BILN 2061, a novel oral HCV serine protease inhibitor, in patients with chronic hepatitis C genotype 1. Presented at the 53rd Annual Meeting of AASLD. November 2-5, 2002; Boston, MA. Abstract 866
    Google Scholar
  • 140 Benhamou Y, Hinrichsen H, Sentjens R. et al .Safety, tolerability and antiviral effect of BILN 2061, a novel HCV serine protease inhibitor, after oral treatment over 2 days in patients with chronic hepatitis C, genotype 1, with advanced liver fibrosis. Presented at the 53rd Annual Meeting of AASLD. November 2-5, 2002; Boston, MA. Abstract 563
    Google Scholar
  • 141 Soler M, McHutchison J G, Kwoh J. et al .Treatment of chronic hepatitis C with ISIS 14803, an antisense oligonucleotide inhibitor of HCV. Effect of target region sequence on antiviral efficacy. Presented at the 53rd Annual Meeting of AASLD. November 2-5, 2002; Boston, MA. Abstract 469
    Google Scholar
  • 142 Davis G L, Balan V, Sulkowski M S. et al .A phase 1 study to evaluate the pharmacokinetics, safety, and tolerability of escalating doses of a novel recombinant human albumin-interferon fusion protein (albuferon) in subjects with chronic hepatitis C. Presented at the 53rd Annual Meeting of AASLD. November 2-5, 2002; Boston, MA. Abstract 490
    Google Scholar
  • 143 Eren R, Ilan E, Nussbaum O. et al .Development and clinical evaluation of human monoclonal antibodies for treating HCV infection. Presented at the 53rd Annual Meeting of AASLD. November 2-5, 2002; Boston, MA. Abstract 498
    Google Scholar
  • 144 Yenni P G, Hammer S M, Carpenter C CJ. et al . Antiretroviral treatment for adult HIV infection in 2002; updated recommendations of the International AIDS Society-USA Panel.  JAMA . 2002;  288 222-235
    CrossrefPubMedGoogle Scholar
  • 145 The Panel on Clinical Practices for Treatment of HIV Infection convened by the Department of Health and Human Services (DHHS). Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents [on-line] February 4, 2002. Available: aidsinfo.nih.gov/guidelines/default dbz.asp?id=50; accessed December 7 2002
  • 146 Torre D, Tambini R, Cadario F. et al . Evolution of coinfection with human immunodeficiency virus and hepatitis C virus in patients treated with highly active antiretroviral therapy.  Clin Infect Dis . 2001;  33 1579-1585
    CrossrefPubMedGoogle Scholar
  • 147 Fellay J, Boubaker K, Ledergerber B. et al . Prevalence of adverse events associated with potent antiretroviral treatment: Swiss HIV Cohort Study.  Lancet . 2001;  358 1322-1327
    CrossrefPubMedGoogle Scholar
  • 148 Centers for Disease Control and Prevention. Serious adverse events attributed to nevirapine regimens for postexposure prophylaxis after HIV exposures worldwide, 1997-2000.  Morb Mortal Wkly Rep . 2001;  49 1153-1156
    PubMedGoogle Scholar
  • 149 Randall G, Rice C M. Hepatitis C virus cell culture replication systems: their potential use for the development of antiviral therapies.  Curr Opin Infect Dis . 2001;  14 743-747
    PubMedGoogle Scholar
      >