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HCV and HIV co-infection: mechanisms and management

Key Points

  • Patients co-infected with HCV and HIV are at increased risk of accelerated disease progression, resulting in higher rates of liver decompensation and death compared with patients monoinfected with HCV

  • HIV accelerates HCV-related fibrosis progression through multiple mechanisms

  • HIV suppression seems to reduce fibrosis progression and decrease rates of hepatic decompensation among co-infected patients

  • Successful HCV therapy is associated with a halting of fibrosis progression and decreased complications from end-stage liver disease, but historical rates of sustained virologic response have been significantly lower among co-infected patients than those for chronic HCV monoinfection

  • Promising data exist for all-oral direct-acting antiviral agents suggesting improved efficacy and tolerability, which supports their use in co-infection

Abstract

HCV and HIV co-infection is associated with accelerated hepatic fibrosis progression and higher rates of liver decompensation and death compared to HCV monoinfection, and liver disease is a leading cause of non-AIDS-related mortality among HIV-infected patients. New insights have revealed multiple mechanisms by which HCV and HIV lead to accelerated disease progression, specifically that HIV infection increases HCV replication, augments HCV-induced hepatic inflammation, increases hepatocyte apoptosis, increases microbial translocation from the gut and leads to an impairment of HCV-specific immune responses. Treatment of HIV with antiretroviral therapy and treatment of HCV have independently been shown to delay the progression of fibrosis and reduce complications from end-stage liver disease among co-infected patients. However, rates of sustained virologic response with PEG-IFN and ribavirin have been significantly inferior among co-infected patients compared with HCV-monoinfected patients, and treatment uptake has remained low given the limited efficacy and tolerability of current HCV regimens. With multiple direct-acting antiviral agents in development to treat HCV, a unique opportunity exists to redefine the treatment paradigm for co-infected patients, which incorporates data on fibrosis stage as well as potential drug interactions with antiretroviral therapy.

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Figure 1: Driving factors underlying liver disease pathogenesis in HCV–HIV co-infection.
Figure 2: Interactions between HCV and HIV in hepatocytes and HSCs that contribute to hepatic fibrogenesis.
Figure 3

References

  1. 1

    World Health Organization. Global Health Observatory: HIV/AIDS. WHO [online], (2014).

  2. 2

    Kim, A. Y. & Chung, R. T. Coinfection with HIV-1 and HCV—a one-two punch. Gastroenterology 137, 795–814 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. 3

    Rotman, Y. & Liang, T. J. Coinfection with hepatitis C virus and human immunodeficiency virus: virological, immunological, and clinical outcomes. J. Virol. 83, 7366–7374 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. 4

    Koziel, M. J. & Peters, M. G. Viral hepatitis in HIV infection. N. Engl. J. Med. 356, 1445–1454 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. 5

    Smith, C. et al. Factors associated with specific causes of death amongst HIV-positive individuals in the D:A:D Study. AIDS 24, 1537–1548 (2010).

    Article  PubMed  Google Scholar 

  6. 6

    Gerberding, J. L. Incidence and prevalence of human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and cytomegalovirus among health care personnel at risk for blood exposure: final report from a longitudinal study. J. Infect. Dis. 170, 1410–1417 (1994).

    Article  CAS  PubMed  Google Scholar 

  7. 7

    Garten, R. J. et al. Rapid transmission of hepatitis C virus among young injecting heroin users in Southern China. Int. J. Epidemiol. 33, 182–188 (2004).

    Article  PubMed  Google Scholar 

  8. 8

    Quan, V. M. et al. Risks for HIV, HBV, and HCV infections among male injection drug users in northern Vietnam: a case–control study. AIDS Care 21, 7–16 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9

    Rauch, A. 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. 41, 395–402 (2005).

    Article  PubMed  Google Scholar 

  10. 10

    Eyster, M. E. et al. Heterosexual co-transmission of hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Ann. Intern. Med. 115, 764–768 (1991).

    Article  CAS  PubMed  Google Scholar 

  11. 11

    Thomas, D. L. et al. Perinatal transmission of hepatitis C virus from human immunodeficiency virus type 1-infected mothers. Women and Infants Transmission Study. J. Infect. Dis. 177, 1480–1488 (1998).

    Article  CAS  PubMed  Google Scholar 

  12. 12

    Hershow, R. C. et al. Increased vertical transmission of human immunodeficiency virus from hepatitis C virus-coinfected mothers. Women and Infants Transmission Study. J. Infect. Dis. 176, 414–420 (1997).

    Article  CAS  PubMed  Google Scholar 

  13. 13

    Polis, C. B. et al. Impact of maternal HIV coinfection on the vertical transmission of hepatitis C virus: a meta-analysis. Clin. Infect. Dis. 44, 1123–1131 (2007).

    Article  PubMed  Google Scholar 

  14. 14

    Pappalardo, B. L. Influence of maternal human immunodeficiency virus (HIV) co-infection on vertical transmission of hepatitis C virus (HCV): a meta-analysis. Int. J. Epidemiol. 32, 727–734 (2003).

    Article  PubMed  Google Scholar 

  15. 15

    A significant sex—but not elective cesarean section—effect on mother-to-child transmission of hepatitis C virus infection. J. Infect. Dis. 192, 1872–1879 (2005).

  16. 16

    Marine-Barjoan, E. et al. HCV/HIV co-infection, HCV viral load and mode of delivery: risk factors for mother-to-child transmission of hepatitis C virus? AIDS 21, 1811–1815 (2007).

    Article  PubMed  Google Scholar 

  17. 17

    Sulkowski, M. S. & Thomas, D. L. Hepatitis C in the HIV-infected person. Ann. Intern. Med. 138, 197–207 (2003).

    Article  PubMed  Google Scholar 

  18. 18

    Gotz, H. M. et al. A cluster of acute hepatitis C virus infection among men who have sex with men—results from contact tracing and public health implications. AIDS 19, 969–974 (2005).

    Article  PubMed  Google Scholar 

  19. 19

    van de Laar, T. et al. Evidence of a large, international network of HCV transmission in HIV-positive men who have sex with men. Gastroenterology 136, 1609–1617 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20

    Giraudon, I. et al. Increase in diagnosed newly acquired hepatitis C in HIV-positive men who have sex with men across London and Brighton, 2002–2006: is this an outbreak? Sex. Transm. Infect. 84, 111–115 (2008).

    Article  CAS  PubMed  Google Scholar 

  21. 21

    van de Laar, T. J. et al. Increase in HCV incidence among men who have sex with men in Amsterdam most likely caused by sexual transmission. J. Infect. Dis. 196, 230–238 (2007).

    Article  PubMed  Google Scholar 

  22. 22

    Gamage, D. G. et al. Incidence of hepatitis-C among HIV infected men who have sex with men (MSM) attending a sexual health service: a cohort study. BMC Infect. Dis. 11, 39 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  23. 23

    Wandeler, G. et al. Hepatitis C virus infections in the Swiss HIV Cohort Study: a rapidly evolving epidemic. Clin. Infect. Dis. 55, 1408–1416 (2012).

    Article  PubMed  Google Scholar 

  24. 24

    Brook, G. et al. British HIV Association guidelines for the management of coinfection with HIV-1 and hepatitis B or C virus 2010. HIV Med. 11, 1–30 (2010).

    Article  CAS  PubMed  Google Scholar 

  25. 25

    Rockstroh, J. K. 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. 9, 82–88 (2008).

    Article  CAS  PubMed  Google Scholar 

  26. 26

    European AIDS Treatment Network (NEAT) Acute Hepatitis C Infection Consensus Panel. Acute hepatitis C in HIV-infected individuals: recommendations from the European AIDS Treatment Network (NEAT) consensus conference. AIDS 25, 399–409 (2011).

  27. 27

    Rein, D. B. et al. The cost-effectiveness of birth-cohort screening for hepatitis C antibody in US primary care settings. Ann. Intern. Med. 156, 263–270 (2012).

    Article  PubMed  Google Scholar 

  28. 28

    Hernando, V. et al. All-cause and liver-related mortality in HIV positive subjects compared to the general population: differences by HCV co-infection. J. Hepatol. 57, 743–751 (2012).

    Article  PubMed  Google Scholar 

  29. 29

    Chen, T. Y. et al. Meta-analysis: increased mortality associated with hepatitis C in HIV-infected persons is unrelated to HIV disease progression. Clin. Infect. Dis. 49, 1605–1615 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  30. 30

    Eyster, M. E. et al. Increasing hepatitis C virus RNA levels in hemophiliacs: relationship to human immunodeficiency virus infection and liver disease. Multicenter Hemophilia Cohort Study. Blood 84, 1020–1023 (1994).

    CAS  PubMed  Google Scholar 

  31. 31

    Alter, M. J. et al. The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team. N. Engl. J. Med. 327, 1899–1905 (1992).

    Article  CAS  PubMed  Google Scholar 

  32. 32

    Thomas, D. L. et al. The natural history of hepatitis C virus infection: host, viral, and environmental factors. JAMA 284, 450–456 (2000).

    Article  CAS  PubMed  Google Scholar 

  33. 33

    Benhamou, Y. et al. Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. The Multivirc Group. Hepatology 30, 1054–1058 (1999).

    Article  CAS  PubMed  Google Scholar 

  34. 34

    Sulkowski, M. S. et al. Rapid fibrosis progression among HIV/hepatitis C virus-co-infected adults. AIDS 21, 2209–2216 (2007).

    Article  PubMed  Google Scholar 

  35. 35

    Ghany, M. G. et al. Progression of fibrosis in chronic hepatitis C. Gastroenterology 124, 97–104 (2003).

    Article  PubMed  Google Scholar 

  36. 36

    Ryder, S. D. et al. Progression of hepatic fibrosis in patients with hepatitis C: a prospective repeat liver biopsy study. Gut 53, 451–455 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. 37

    Macias, J. et al. Fast fibrosis progression between repeated liver biopsies in patients coinfected with human immunodeficiency virus/hepatitis C virus. Hepatology 50, 1056–1063 (2009).

    Article  CAS  PubMed  Google Scholar 

  38. 38

    Brau, N. et al. Slower fibrosis progression in HIV/HCV-coinfected patients with successful HIV suppression using antiretroviral therapy. J. Hepatol. 44, 47–55 (2006).

    Article  CAS  PubMed  Google Scholar 

  39. 39

    Verma, S. et al. Do type and duration of antiretroviral therapy attenuate liver fibrosis in HIV-hepatitis C virus-coinfected patients? Clin. Infect. Dis. 42, 262–270 (2006).

    Article  CAS  PubMed  Google Scholar 

  40. 40

    Sterling, R. K. et al. Similar progression of fibrosis between HIV/HCV-infected and HCV-infected patients: analysis of paired liver biopsy samples. Clin. Gastroenterol. Hepatol. 8, 1070–1076 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  41. 41

    Thein, H. H. et al. Natural history of hepatitis C virus infection in HIV-infected individuals and the impact of HIV in the era of highly active antiretroviral therapy: a meta-analysis. AIDS 22, 1979–1991 (2008).

    Article  PubMed  Google Scholar 

  42. 42

    Graham, C. S. et al. Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis. Clin. Infect. Dis. 33, 562–569 (2001).

    Article  CAS  PubMed  Google Scholar 

  43. 43

    Pineda, J. A. et al. HIV coinfection shortens the survival of patients with hepatitis C virus-related decompensated cirrhosis. Hepatology 41, 779–789 (2005).

    Article  PubMed  Google Scholar 

  44. 44

    Pineda, J. A. et al. Natural history of compensated hepatitis C virus-related cirrhosis in HIV-infected patients. Clin. Infect. Dis. 49, 1274–1282 (2009).

    Article  PubMed  Google Scholar 

  45. 45

    Giron-Gonzalez, J. A. et al. Natural history of compensated and decompensated HCV-related cirrhosis in HIV-infected patients: a prospective multicentre study. Antivir. Ther. 12, 899–907 (2007).

    CAS  PubMed  Google Scholar 

  46. 46

    Brau, N. et al. Presentation and outcome of hepatocellular carcinoma in HIV-infected patients: a US–Canadian multicenter study. J. Hepatol. 47, 527–537 (2007).

    Article  PubMed  Google Scholar 

  47. 47

    Verma, S. HAART attenuates liver fibrosis in patients with HIV/HCV co-infection: fact or fiction? J. Antimicrob. Chemother. 58, 496–501 (2006).

    Article  CAS  PubMed  Google Scholar 

  48. 48

    Lin, W. et al. HIV increases HCV replication in a TGF-β1-dependent manner. Gastroenterology 134, 803–811 (2008).

    Article  CAS  PubMed  Google Scholar 

  49. 49

    Jang, J. Y. et al. HIV infection increases HCV-induced hepatocyte apoptosis. J. Hepatol. 54, 612–620 (2011).

    Article  PubMed  Google Scholar 

  50. 50

    Zheng, S. J. et al. Critical roles of TRAIL in hepatic cell death and hepatic inflammation. J. Clin. Invest. 113, 58–64 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. 51

    Lin, W. et al. Hepatitis C virus regulates transforming growth factor β1 production through the generation of reactive oxygen species in a nuclear factor κB-dependent manner. Gastroenterology 138, 2509–2518 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. 52

    Lin, W. et al. HIV and HCV cooperatively promote hepatic fibrogenesis via induction of reactive oxygen species and NFκB. J. Biol. Chem. 286, 2665–2674 (2011).

    Article  CAS  PubMed  Google Scholar 

  53. 53

    Tuyama, A. C. et al. Human immunodeficiency virus (HIV)-1 infects human hepatic stellate cells and promotes collagen I and monocyte chemoattractant protein-1 expression: implications for the pathogenesis of HIV/hepatitis C virus-induced liver fibrosis. Hepatology 52, 612–622 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. 54

    Veazey, R. S. et al. Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 280, 427–431 (1998).

    Article  CAS  PubMed  Google Scholar 

  55. 55

    Brenchley, J. M. et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat. Med. 12, 1365–1371 (2006).

    Article  CAS  PubMed  Google Scholar 

  56. 56

    Seki, E. et al. TLR4 enhances TGF-β signaling and hepatic fibrosis. Nat. Med. 13, 1324–1332 (2007).

    Article  CAS  PubMed  Google Scholar 

  57. 57

    Balagopal, A. et al. Human immunodeficiency virus-related microbial translocation and progression of hepatitis C. Gastroenterology 135, 226–233 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. 58

    Flynn, J. K. et al. Impaired hepatitis C virus (HCV)-specific interferon-γ responses in individuals with HIV who acquire HCV infection: correlation with CD4(+) T-cell counts. J. Infect. Dis. 206, 1568–1576 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. 59

    Kim, A. Y. et al. Impaired hepatitis C virus-specific T cell responses and recurrent hepatitis C virus in HIV coinfection. PLoS Med. 3, e492 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. 60

    Morishima, C. et al. Decreased NK cell frequency in chronic hepatitis C does not affect ex vivo cytolytic killing. Hepatology 43, 573–580 (2006).

    Article  PubMed  Google Scholar 

  61. 61

    Glassner, A. et al. Impaired CD4(+) T cell stimulation of NK cell anti-fibrotic activity may contribute to accelerated liver fibrosis progression in HIV/HCV patients. J. Hepatol. 59, 427–433 (2013).

    Article  CAS  PubMed  Google Scholar 

  62. 62

    Palmateer, N. et al. Evidence for the effectiveness of sterile injecting equipment provision in preventing hepatitis C and human immunodeficiency virus transmission among injecting drug users: a review of reviews. Addiction 105, 844–859 (2010).

    Article  PubMed  Google Scholar 

  63. 63

    Blome, M. A. et al. Minimal transmission of HIV despite persistently high transmission of hepatitis C virus in a Swedish needle exchange program. J. Viral Hepat. 18, 831–839 (2011).

    Article  PubMed  Google Scholar 

  64. 64

    Paintsil, E., He, H., Peters, C., Lindenbach, B. D. & Heimer, R. Survival of hepatitis C virus in syringes: implication for transmission among injection drug users. J. Infect. Dis. 202, 984–990 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  65. 65

    Martin, T. C. et al. Hepatitis C virus reinfection incidence and treatment outcome among HIV-positive MSM. AIDS 27, 2551–2557 (2013).

    Article  PubMed  Google Scholar 

  66. 66

    Walensky, R. P. et al. Cost-effectiveness of HIV treatment as prevention in serodiscordant couples. N. Engl. J. Med. 369, 1715–1725 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. 67

    Thomas, D. L. Global control of hepatitis C: where challenge meets opportunity. Nat. Med. 19, 850–858 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. 68

    Qurishi, N. et al. Effect of antiretroviral therapy on liver-related mortality in patients with HIV and hepatitis C virus coinfection. Lancet 362, 1708–1713 (2003).

    Article  CAS  PubMed  Google Scholar 

  69. 69

    Limketkai, B. N. et al. Relationship of liver disease stage and antiviral therapy with liver-related events and death in adults coinfected with HIV/HCV. JAMA 308, 370–378 (2012).

    Article  CAS  PubMed  Google Scholar 

  70. 70

    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. AIDSinfo [online].

  71. 71

    European AIDS Clinical Society. Guidelines, Version 7.0, October 2013. European AIDS Clinical Society [online], (2013).

  72. 72

    Aranzabal, L. et al. Influence of liver fibrosis on highly active antiretroviral therapy-associated hepatotoxicity in patients with HIV and hepatitis C virus coinfection. Clin. Infect. Dis. 40, 588–593 (2005).

    Article  CAS  PubMed  Google Scholar 

  73. 73

    Dorward, J. et al. Successful treatment of acute hepatitis C virus in HIV positive patients using the European AIDS Treatment Network guidelines for treatment duration. J. Clin. Virol. 52, 367–369 (2011).

    Article  CAS  PubMed  Google Scholar 

  74. 74

    Webster, D. P. et al. Spontaneous clearance and treatment of acute hepatitis C infection in HIV-positive men with 48 weeks of interferon-α and ribavirin. Int. J. STD AIDS 24, 179–183 (2013).

    Article  CAS  PubMed  Google Scholar 

  75. 75

    Broers, B. et al. Barriers to interferon-α therapy are higher in intravenous drug users than in other patients with acute hepatitis C. J. Hepatol. 42, 323–328 (2005).

    Article  CAS  PubMed  Google Scholar 

  76. 76

    Wiegand, J. et al. Early monotherapy with pegylated interferon α-2b for acute hepatitis C infection: the HEP-NET acute HCV-II study. Hepatology 43, 250–256 (2006).

    Article  CAS  PubMed  Google Scholar 

  77. 77

    Fierer, D. S. et al. Telaprevir in the treatment of acute hepatitis C infection in HIV-infected men. Clin. Infect. Dis. http://dx.doi.org/10.1093/cid/cit799.

  78. 78

    van der Meer, A. J. et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA 308, 2584–2593 (2012).

    Article  CAS  PubMed  Google Scholar 

  79. 79

    Backus, L. I. et al. A sustained virologic response reduces risk of all-cause mortality in patients with hepatitis C. Clin. Gastroenterol. Hepatol. 9, 509–516.e1 (2011).

    Article  PubMed  Google Scholar 

  80. 80

    Imazeki, F. et al. Favorable prognosis of chronic hepatitis C after interferon therapy by long-term cohort study. Hepatology 38, 493–502 (2003).

    Article  CAS  PubMed  Google Scholar 

  81. 81

    Shiratori, Y. et al. Antiviral therapy for cirrhotic hepatitis C: association with reduced hepatocellular carcinoma development and improved survival. Ann. Intern. Med. 142, 105–114 (2005).

    Article  CAS  PubMed  Google Scholar 

  82. 82

    Veldt, B. J. et al. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Ann. Intern. Med. 147, 677–684 (2007).

    Article  PubMed  Google Scholar 

  83. 83

    Berenguer, J. 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 50, 407–413 (2009).

    Article  CAS  PubMed  Google Scholar 

  84. 84

    Mira, J. A. et al. Benefits from sustained virologic response to pegylated interferon plus ribavirin in HIV/hepatitis C virus-coinfected patients with compensated cirrhosis. Clin. Infect. Dis. 56, 1646–1653 (2013).

    Article  CAS  PubMed  Google Scholar 

  85. 85

    Fierer, D. S. et al. Rapid progression to decompensated cirrhosis, liver transplant, and death in HIV-infected men after primary hepatitis C virus infection. Clin. Infect. Dis. 56, 1038–1043 (2013).

    Article  PubMed  Google Scholar 

  86. 86

    Macias, J. et al. Risk of liver decompensation among HIV/hepatitis C virus-coinfected individuals with advanced fibrosis: implications for the timing of therapy. Clin. Infect. Dis. 57, 1401–1408 (2013).

    Article  CAS  PubMed  Google Scholar 

  87. 87

    Laguno, M. et al. Randomized trial comparing pegylated interferon α-2b versus pegylated interferon α-2a, both plus ribavirin, to treat chronic hepatitis C in human immunodeficiency virus patients. Hepatology 49, 22–31 (2009).

    Article  CAS  PubMed  Google Scholar 

  88. 88

    Torriani, F. J. et al. Peginterferon α-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N. Engl. J. Med. 351, 438–450 (2004).

    Article  CAS  PubMed  Google Scholar 

  89. 89

    Chung, R. T. et al. Peginterferon α-2a plus ribavirin versus interferon α-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N. Engl. J. Med. 351, 451–459 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. 90

    Carrat, F. et al. Pegylated interferon α-2b vs standard interferon α-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. JAMA 292, 2839–2848 (2004).

    Article  CAS  PubMed  Google Scholar 

  91. 91

    Voigt, E. et al. Pegylated interferon α-2b plus ribavirin for the treatment of chronic hepatitis C in HIV-coinfected patients. J. Infect. 53, 36–42 (2006).

    Article  PubMed  Google Scholar 

  92. 92

    Rodriguez-Torres, M. et al. Peginterferon α-2a plus ribavirin for HIV–HCV genotype 1 coinfected patients: a randomized international trial. HIV Clin. Trials 13, 142–152 (2012).

    Article  CAS  PubMed  Google Scholar 

  93. 93

    Zylberberg, H. et al. Safety and efficacy of interferon-ribavirin combination therapy in HCV–HIV coinfected subjects: an early report. Gut 47, 694–697 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. 94

    Manns, M. P. et al. Peginterferon α-2b plus ribavirin compared with interferon α-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 358, 958–965 (2001).

    Article  CAS  PubMed  Google Scholar 

  95. 95

    Barcaui, H. S. et al. Low rates of sustained virologic response with peginterferon plus ribavirin for chronic hepatitis C virus infection in HIV infected patients in Rio de Janeiro, Brazil. PLoS ONE 8, e67734 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. 96

    Nunez, M. 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 23, 972–982 (2007).

    Article  CAS  PubMed  Google Scholar 

  97. 97

    Moreno, A. et al. High rate of didanosine-related mitochondrial toxicity in HIV/HCV-coinfected patients receiving ribavirin. Antivir. Ther. 9, 133–138 (2004).

    CAS  PubMed  Google Scholar 

  98. 98

    Bani-Sadr, F. et al. Risk factors for symptomatic mitochondrial toxicity in HIV/hepatitis C virus-coinfected patients during interferon plus ribavirin-based therapy. J. Acquir. Immune Defic. Syndr. 40, 47–52 (2005).

    Article  CAS  PubMed  Google Scholar 

  99. 99

    Brau, N. Epoetin α treatment for acute anaemia during interferon plus ribavirin combination therapy for chronic hepatitis C. J. Viral Hepat. 11, 191–197 (2004).

    Article  CAS  PubMed  Google Scholar 

  100. 100

    Mauss, S. et al. Risk factors for hepatic decompensation in patients with HIV/HCV coinfection and liver cirrhosis during interferon-based therapy. AIDS 18, F21–F25 (2004).

    Article  CAS  PubMed  Google Scholar 

  101. 101

    Lafeuillade, A., Hittinger, G. & Chadapaud, S. Increased mitochondrial toxicity with ribavirin in HIV/HCV coinfection. Lancet 357, 280–281 (2001).

    Article  CAS  PubMed  Google Scholar 

  102. 102

    Sulkowski, M. S. et al. Combination therapy with telaprevir for chronic hepatitis C virus genotype 1 infection in patients with HIV: a randomized trial. Ann. Intern. Med. 159, 86–96 (2013).

    PubMed  Google Scholar 

  103. 103

    Sulkowski, M. et al. Boceprevir versus placebo with pegylated interferon α-2b and ribavirin for treatment of hepatitis C virus genotype 1 in patients with HIV: a randomised, double-blind, controlled phase 2 trial. Lancet Infect. Dis. 13, 597–605 (2013).

    Article  CAS  PubMed  Google Scholar 

  104. 104

    Jacobson, I. M. et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N. Engl. J. Med. 364, 2405–2416 (2011).

    Article  CAS  PubMed  Google Scholar 

  105. 105

    Montes, M. et al. Telaprevir combination therapy in treatment-naive and experienced patients co-infected with HCV and HIV [abstract 38]. Presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases, Washington DC (2013).

  106. 106

    Cotte, L. et al. High End-Of-Treatment (EOT) response rate with Telaprevir-PegIFN-RBV in treatment-experienced HIV coinfected patients with HCV genotype 1: ANRS HC26 TelapreVIH study [Poster 1108]. Presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases, Washington DC (2013).

  107. 107

    Poizot-Martin, I. et al. W48 Response rate of Boceprevir-PegIFN-RBV in treatment-experienced HIV coinfected patients with HCV genotype 1: ANRS-HC27 BocepreVIH study [Poster 1105]. Presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases, Washington, DC (2013).

  108. 108

    Dieterich, D. et al. Simeprevir (TMC435) plus peginterferon/ribavirin in patients co-infected with HCV genotype-1 and HIV-1: primary analysis of the C212 study [abstract LBPS9/5]. Presented at the 14th European AIDS Conference (EACS), Brussels (2013).

  109. 109

    Rockstroh, J. K. et al. STARTVerso4 Phase III tiral of faldaprevir plus peg interferon alfa-2a and ribavirin (PR) in patients with HIV and HCV genotype 1 coinfection: end of treatment response [Poster 1099]. Presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases, Washington, DC (2013).

  110. 110

    Lawitz, E. et al. Sofosbuvir in combination with peginterferon α-2a and ribavirin for non-cirrhotic, treatment-naive patients with genotypes 1, 2, and 3 hepatitis C infection: a randomised, double-blind, phase 2 trial. Lancet Infect. Dis. 13, 401–408 (2013).

    Article  CAS  PubMed  Google Scholar 

  111. 111

    Lawitz, E. & Gane, E. J. Sofosbuvir for previously untreated chronic hepatitis C infection. N. Engl. J. Med. 369, 678–679 (2013).

    Article  Google Scholar 

  112. 112

    Jacobson, I. M. et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N. Engl. J. Med. 368, 1867–1877 (2013).

    Article  CAS  Google Scholar 

  113. 113

    Sulkowski, M. S. et al. All-oral therapy with sofosbuvir plus ribavirin for the treatment of HCV genotype 1, 2, and 3 infection in patients co-infected with HIV (PHOTON-1) [abstract 212]. Presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases, Washington DC (2013).

  114. 114

    Osinusi, A. et al. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial. JAMA 310, 804–811 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. 115

    Lawitz, E. et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet http://dx.doi.org/10.1016/S0140-6737(13)62121-2.

  116. 116

    Jacobson, I. M. et al. SVR results of a once-daily regimen of simeprevir (SMV, TMC435) plus sofosbuvir (SOF, GS-7977) with or without ribavirin in cirrhotic and non-cirrhotic HCV genotype 1 treatment-naïve and prior null responder patients: the COSMOS study [abstract LB-3]. Presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases, Washington, DC (2013).

  117. 117

    US National Library of Medicine. ClinicalTrials.gov [online], (2013).

  118. 118

    US National Library of Medicine. ClinicalTrials.gov [online], (2013).

  119. 119

    Ge, D. et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461, 399–401 (2009).

    Article  CAS  PubMed  Google Scholar 

  120. 120

    Tanaka, Y. et al. Genome-wide association of IL28B with response to pegylated interferon-α and ribavirin therapy for chronic hepatitis C. Nat. Genet. 41, 1105–1109 (2009).

    Article  CAS  PubMed  Google Scholar 

  121. 121

    Rallon, N. I. et al. Association of a single nucleotide polymorphism near the interleukin-28B gene with response to hepatitis C therapy in HIV/hepatitis C virus-coinfected patients. AIDS 24, F23–F29 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. 122

    Thompson, A. J. et al. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology 139, 120–129 (2010).

    Article  CAS  PubMed  Google Scholar 

  123. 123

    Rivero-Juarez, A. et al. The IL28B effect on hepatitis C virus kinetics among HIV patients after the first weeks of pegylated-interferon/ribavirin treatment varies according to hepatitis C virus-1 subtype. AIDS 27, 1941–1947 (2013).

    Article  CAS  PubMed  Google Scholar 

  124. 124

    Resino, S., Sanchez-Conde, M. & Berenguer, J. Coinfection by human immunodeficiency virus and hepatitis C virus: noninvasive assessment and staging of fibrosis. Curr. Opin. Infect. Dis. 25, 564–569 (2012).

    Article  PubMed  Google Scholar 

  125. 125

    Bambha, K. et al. Assessing mortality in women with hepatitis C virus and HIV using indirect markers of fibrosis. AIDS 26, 599–607 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  126. 126

    Nunes, D. et al. HIV infection does not affect the performance of noninvasive markers of fibrosis for the diagnosis of hepatitis C virus-related liver disease. J. Acquir. Immune Defic. Syndr. 40, 538–544 (2005).

    Article  PubMed  Google Scholar 

  127. 127

    Fernandez-Montero, J. V. et al. Liver stiffness predicts liver-related complications and mortality in HIV patients with chronic hepatitis C on antiretroviral therapy. AIDS 27, 1129–1134 (2013).

    Article  CAS  PubMed  Google Scholar 

  128. 128

    Soriano, V. et al. Regression of liver fibrosis in hepatitis C virus/HIV-co-infected patients after treatment with pegylated interferon plus ribavirin. AIDS 20, 2225–2227 (2006).

    Article  PubMed  Google Scholar 

  129. 129

    Macias, J. et al. Changes in liver stiffness in patients with chronic hepatitis C with and without HIV co-infection treated with pegylated interferon plus ribavirin. J. Antimicrob. Chemother. 65, 2204–2211 (2010).

    Article  CAS  PubMed  Google Scholar 

  130. 130

    Hernandez-Gea, V. & Friedman, S. L. Pathogenesis of liver fibrosis. Annu. Rev. Pathol. 6, 425–456 (2011).

    Article  CAS  PubMed  Google Scholar 

  131. 131

    Choi, J. Oxidative stress, endogenous antioxidants, alcohol, and hepatitis C: pathogenic interactions and therapeutic considerations. Free Radic. Biol. Med. 52, 1135–1150 (2012).

    Article  CAS  PubMed  Google Scholar 

  132. 132

    Guicciardi, M. E. & Gores, G. J. Apoptosis: a mechanism of acute and chronic liver injury. Gut 54, 1024–1033 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. 133

    Zhan, S. S. et al. Phagocytosis of apoptotic bodies by hepatic stellate cells induces NADPH oxidase and is associated with liver fibrosis in vivo. Hepatology 43, 435–443 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. 134

    Canbay, A. et al. Apoptotic body engulfment by a human stellate cell line is profibrogenic. Lab. Invest. 83, 655–663 (2003).

    Article  CAS  PubMed  Google Scholar 

  135. 135

    Wang, K. et al. Hepatic apoptosis can modulate liver fibrosis through TIMP1 pathway. Apoptosis 18, 566–577 (2013).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The work of the authors is supported by HHS/NIH grants T32DK007191 (J.Y.C.), DK098079 and DA033541 (R.T.C.) and by the Harvard University Center for AIDS Research (HU CFAR NIH/NIAID fund 5P30AI060354-09 to E.R.F.).

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Correspondence to Raymond T. Chung.

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R.T.C. has acted as a consultant for Abbvie and has received research grant support from Gilead Sciences. J.Y.C. and E.R.F. declare no competing interests.

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Chen, J., Feeney, E. & Chung, R. HCV and HIV co-infection: mechanisms and management. Nat Rev Gastroenterol Hepatol 11, 362–371 (2014). https://doi.org/10.1038/nrgastro.2014.17

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