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Hepatitis C in HIV-Infected Patients: Impact of Direct-Acting Antivirals

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Abstract

Approximately 30 % of HIV-infected patients are co-infected with hepatitis C virus (HCV). After the release of highly active antiretroviral therapy, liver disease has become the leading cause of morbidity and mortality in HIV patients. Prior to 2011, HCV treatment with pegylated-interferon and ribavirin in HCV/HIV co-infected patients only allowed 14–38 % of patients with HCV genotype 1 to achieve a sustained virologic response (SVR). Additionally, treatment was commonly discontinued as a result of adverse events. Recently, simeprevir and sofosbuvir have been approved by the US Food and Drug Administration (FDA) for HCV mono-infection. Sofosbuvir has been given FDA approval in co-infected patients offering unprecedented SVR rates and the potential for interferon-free therapy. HCV therapies that are in the pipeline offer improved treatment times, safety profiles, and rates of SVR. Despite these improvements, several new issues including adherence, drug–drug interactions with antiretroviral therapies, adverse events, resistance, and patient selection may complicate therapy. This article reviews the current status of direct-acting antivirals (DAA)-containing regimens for HIV/HCV co-infected patients in the USA. New results investigating telaprevir and boceprevir are also discussed as they are relevant for locations where new DAAs are not available. The impact future interferon-free therapies may have on co-infected patients is also discussed.

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References

  1. Weber R, Ruppik M, Rickenbach M, Spoerri A, Furrer H, Battegay M, et al. Decreasing mortality and changing patterns of causes of death in the Swiss HIV Cohort Study. HIV Med. 2013;14(4):195–207.

    Article  CAS  PubMed  Google Scholar 

  2. Smith C, Sabin CA, Lundgren JD, Thiebaut R, Weber R, Law M, et al. Factors associated with specific causes of death amongst HIV-positive individuals in the D:A:D Study. AIDS (London, England). 2010;24(10):1537–48.

    Google Scholar 

  3. 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(1):150–4.

  4. Rockstroh JK, Mocroft A, Soriano V, Tural C, Losso MH, Horban A, et al. Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy. J Infect Dis. 2005;192(6):992–1002.

    Article  PubMed  Google Scholar 

  5. Soriano V, Mocroft A, Rockstroh J, Ledergerber B, Knysz B, Chaplinskas S, et al. Spontaneous viral clearance, viral load, and genotype distribution of hepatitis C virus (HCV) in HIV-infected patients with anti-HCV antibodies in Europe. J Infect Dis. 2008;198(9):1337–44.

    Article  PubMed  Google Scholar 

  6. Benhamou Y, Bochet M, Di Martino V, Charlotte F, Azria F, Coutellier A, et al. Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients: the Multivirc Group. Hepatology. 1999;30(4):1054–8.

    Article  CAS  PubMed  Google Scholar 

  7. Dieterich DT, Rodriguez-Torres M, Sulkowski MS, Torriani F, Wat C, Patel KM, et al. In APRICOT and PARADIGM 99% of HIV-HCV co-infected patients with an SVR12 achieved an SVR24 validating SVR12 as an endpoint for trials in this population. Hepatology. 2012;56:587A–8A.

    Google Scholar 

  8. Berenguer J, Alvarez-Pellicer J, Carrero A, Von Wichmann MA, Lopez-Aldeguer J, Mallolas J, et al. Clinical effects of viral relapse after interferon plus ribavirin in patients co-infected with human immunodeficiency virus and hepatitis C virus. J Hepatol. 2013;58(6):1104–12.

    Article  CAS  PubMed  Google Scholar 

  9. Berenguer J, Alvarez-Pellicer J, Martin PM, Lopez-Aldeguer J, Von-Wichmann MA, Quereda C, et al. Sustained virological response to interferon plus ribavirin reduces liver-related complications and mortality in patients coinfected with human immunodeficiency virus and hepatitis C virus. Hepatology. 2009;50(2):407–13.

    Article  CAS  PubMed  Google Scholar 

  10. Berenguer J, Rodriguez E, Miralles P, Von Wichmann MA, Lopez-Aldeguer J, Mallolas J, et al. Sustained virological response to interferon plus ribavirin reduces non-liver-related mortality in patients coinfected with HIV and hepatitis C virus. Clin Infect Dis. 2012;55(5):728–36.

    Article  CAS  PubMed  Google Scholar 

  11. van der Meer AJ, Veldt BJ, Feld JJ, Wedemeyer H, Dufour JF, Lammert F, et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012;308(24):2584–93.

    Article  PubMed  Google Scholar 

  12. Kramer JR, Kanwal F, Richardson P, Mei M, El-Serag HB. Gaps in the achievement of effectiveness of HCV treatment in national VA practice. J Hepatol. 2012;56(2):320–5.

    Article  PubMed  Google Scholar 

  13. Ogawa E, Furusyo N, Kajiwara E, Takahashi K, Nomura H, Tanabe Y, et al. Evaluation of the adverse effect of premature discontinuation of pegylated interferon alpha-2b and ribavirin treatment for chronic hepatitis C virus infection: results from Kyushu University Liver Disease Study. J Gastroenterol Hepatol. 2012;27(7):1233–40.

    Article  CAS  PubMed  Google Scholar 

  14. Carrat F, Bani-Sadr F, Pol S, Rosenthal E, Lunel-Fabiani F, Benzekri A, 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(23):2839–48.

    Article  CAS  PubMed  Google Scholar 

  15. Chung RT, Andersen J, Volberding P, Robbins GK, Liu T, Sherman KE, 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(5):451–9.

    Article  CAS  PubMed  Google Scholar 

  16. Torriani FJ, Rodriguez-Torres M, Rockstroh JK, Lissen E, Gonzalez-Garcia J, Lazzarin A, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med. 2004;351(5):438–50.

    Article  CAS  PubMed  Google Scholar 

  17. Laguno M, Murillas J, Blanco JL, Martinez E, Miquel R, Sanchez-Tapias JM, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for treatment of HIV/HCV co-infected patients. AIDS. 2004;18(13):F27–36.

  18. Ioannou G, Scott J, Yang Y, Green P, Beste L. Antiviral treatment for hepatitis C virus in HIV/HCV co-infected patients. 64th Annual Meeting of the American Association of the Study of Liver Diseases, Washington, DC; 2013.

  19. American Association for the Study of Liver Diseases and the Infectious Diseases Society of America: recommendations for testing, managing, and treating hepatitis C2014. http://www.hcvguidelines.org/full-report-view.

  20. Galan RJ, Cidoncha EC, Martin MF, Rodriguez CC, Almeida CV, Verdugo RM. Antiviral regimen complexity index as an independent predictor of sustained virologic response in patients with chronic hepatitis C. JMCP. 2013;19(6):448–53.

    PubMed  Google Scholar 

  21. Jacobson IM, Ghalib RH, Rodriguez-Torres M, Younossi ZM, Corregidor A, Sulkowski MS, et al. SVR results of a once-daily regimen of simeprevir (TMC435) plus sofosbuvir (GS-7977) with or without ribavirin in cirrhotic and non-cirrhotic HCV genotype 1 treatment-naive and prior null responder patients: the COSMOS study. Hepatology. 2013;58(6):1379A–80A.

    Google Scholar 

  22. Zeuzem S, Dusheiko G, Salupere R, Mangi A, Flisiak R, Hyland R, et al. Sofosbuvir + ribavirin for 12 or 24 weeks for patients with HCV genotype 2 or 3: the VALENCE trial. 64rd Annual Meeting of the American Association for the Study of Liver Diseases, Washington, DC; 2013.

  23. Hulskotte EGJ, Feng HP, Xuan FJ, van Zutven M, Treitel MA, Hughes EA, et al. Pharmacokinetic interactions between the hepatitis C virus protease inhibitor boceprevir and ritonavir-boosted HIV-1 protease inhibitors atazanavir, darunavir, and lopinavir. Clin Infect Dis. 2013;56(5):718–26.

    Article  CAS  PubMed  Google Scholar 

  24. Dieterich DT, Tural C, Nelson M, Arasteh K, Soriano V, Guardiola JM, et al. Faldaprevir plus pegylated interferon alfa-2a/ribavirin in HIV/HCV coinfection: STARTVerso4. 21st Conference on Retroviruses and Opportunistic Infections, Boston (MA); 2014.

  25. Kasserra C, Hughes E, Treitel M, Gupta S, O’Mara E. Clinical pharmacology of boceprevir: metabolism, excretion, and drug–drug interactions. CROI, Boston (MA); 2011.

  26. Simeprevir package insert. http://www.olysio.com/shared/product/olysio/prescribing-information.pdf. Accessed 30 Dec 2014.

  27. Foster GR, Hezode C, Bronowicki JP, Carosi G, Weiland O, Verlinden L, et al. Telaprevir alone or with peginterferon and ribavirin reduces HCV RNA in patients with chronic genotype 2 but not genotype 3 infections. Gastroenterology. 2011;141(3):881–9 e1.

  28. Buti M, Agarwal K, Horsmans Y, Sievert W, Janczewska E, Zeuzem S, et al. Telaprevir twice daily is noninferior to telaprevir every 8 hours for patients with chronic hepatitis C. Gastroenterology. 2014;146:744–53.

    Article  CAS  PubMed  Google Scholar 

  29. Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S, et al. Telaprevir for retreatment of HCV infection. N Engl J Med. 2011;364(25):2417–28.

    Article  CAS  PubMed  Google Scholar 

  30. Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364(25):2405–16.

    Article  CAS  PubMed  Google Scholar 

  31. Sherman KE, Flamm SL, Afdhal NH, Nelson DR, Sulkowski MS, Everson GT, et al. Response-guided telaprevir combination treatment for hepatitis C virus infection. N Engl J Med. 2011;365(11):1014–24.

    Article  CAS  PubMed  Google Scholar 

  32. Sulkowski MS, Sherman KE, Dieterich DT, Bsharat M, Mahnke L, Rockstroh JK, et al. Combination therapy with telaprevir for chronic hepatitis C virus genotype 1 infection in patients with HIV: a randomized trial. Ann Intern Med. 2013;159(2):86–96.

    PubMed  Google Scholar 

  33. Montes M, Nelson M, Girard P, Sasadeusz J, Horban A, Grinsztejn B, et al. Telaprevir combination therapy in treatment-naive and -experienced patients co-infected with hepatitis C virus and HIV: week 12 analysis of INSIGHT. 64th Annual Meeting of the American Association of the Study of Liver Diseases, Washington, DC; 2013.

  34. van Heeswijk RP, Beumont M, Kauffman RS, Garg V. Review of drug interactions with telaprevir and antiretrovirals. Antiviral Ther. 2013;18(4):553–60.

    Article  Google Scholar 

  35. Kakuda T, Leopold L, Nijs S. Pharmacokinetic interaction between etravirin or rilpivirine and telaprevin in health volunteers: a randomised, two-way crossover trial. 13th PK Workshop, Barcelona; 2012.

  36. Garg V, Chandorkar G, Yang Y, Adda N, McNair L, Alves K, et al. The effect of CYP3A inhibitors and inducers on the pharmacokinetics of telaprevir in healthy volunteers. Br J Clin Pharmacol. 2013;75(2):431–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, Zeuzem S, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011;364(13):1207–17.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364(13):1195–206.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Sulkowski M, Pol S, Mallolas J, Fainboim H, Cooper C, Slim J, et al. Boceprevir versus placebo with pegylated interferon alfa-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. 2013;13(7):597–605.

    Article  CAS  PubMed  Google Scholar 

  40. Manns MP, Bourliere M, Benhamou Y, Pol S, Bonacini M, Trepo C, et al. Potency, safety, and pharmacokinetics of the NS3/4A protease inhibitor BI201335 in patients with chronic HCV genotype-1 infection. J Hepatol. 2011;54(6):1114–22.

    Article  CAS  PubMed  Google Scholar 

  41. Sulkowski MS, Bourliere M, Bronowicki JP, Asselah T, Pawlotsky JM, Shafran SD, et al. Faldaprevir combined with peginterferon alfa-2a and ribavirin in chronic hepatitis C virus genotype-1 patients with prior nonresponse: SILEN-C2 trial. Hepatology. 2013;57(6):2155–63.

    Article  CAS  PubMed  Google Scholar 

  42. Sulkowski MS, Asselah T, Lalezari J, Ferenci P, Fainboim H, Leggett B, et al. Faldaprevir combined with pegylated interferon alfa-2a and ribavirin in treatment-naive patients with chronic genotype 1 HCV: SILEN-C1 trial. Hepatology. 2013;57(6):2143–54.

    Article  CAS  PubMed  Google Scholar 

  43. Dieterich DT, Rockstroh JK, Orkin C, Gutierrez F, Klein M, Reynes J, et al. Simeprevir plus pegIFN/ribavirin in HCV genotype-1/HIV-1 co-infection (Study C212). 21st Conference on Retroviruses and Opportunistic Infections, Boston (MA); 2014.

  44. Kumada H, Suzuki Y, Ikeda K, Toyota J, Karino Y, Chayama K, et al. Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection. Hepatology. 2014.

  45. Lok AS, Gardiner DF, Hezode C, Lawitz EJ, Bourliere M, Everson GT, et al. Randomized trial of daclatasvir and asunaprevir with or without pegIFN/RBV for hepatitis C virus genotype 1 null responders. J Hepatol. 2013.

  46. Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, Jacobson I, et al. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014;370(3):211–21.

    Article  CAS  PubMed  Google Scholar 

  47. Rockstroh JK, Spengler U, Sudhop T, Ewig S, Theisen A, Hammerstein U, et al. Immunosuppression may lead to progression of hepatitis C virus-associated liver disease in hemophiliacs coinfected with HIV. Am J Gastroenterol. 1996;91(12):2563–8.

    CAS  PubMed  Google Scholar 

  48. Opravil M, Sasadeusz J, Cooper DA, Rockstroh JK, Clumeck N, Clotet B, et al. Effect of baseline CD4 cell count on the efficacy and safety of peginterferon alfa-2a (40KD) plus ribavirin in patients with HIV/hepatitis C virus coinfection. J Acquir Immune Defic Syndr. 2008;47(1):36–49.

    Article  CAS  PubMed  Google Scholar 

  49. Hezode C, Fontaine H, Dorival C, Larrey D, Zoulim F, Canva V, et al. Triple therapy in treatment-experienced patients with HCV-cirrhosis in a multicentre cohort of the French Early Access Programme (ANRS CO20-CUPIC): NCT01514890. J Hepatol. 2013;59(3):434–41.

    Article  PubMed  Google Scholar 

  50. Bichoupan K, Schwartz JM, Martel-Laferriere V, Giannattasio ER, Marfo K, Odin JA, et al. Effect of fibrosis on adverse events in patients with hepatitis C treated with telaprevir. Aliment Pharmacol Ther. 2014;39(2):209–16.

    Article  CAS  PubMed  Google Scholar 

  51. Roux P, Lions C, Cohen J, Winnock M, Salmon-Ceron D, Bani-Sadr F, et al. Impact of HCV treatment and depressive symptoms on adherence to HAART among coinfected HIV-HCV patients: results from the ANRS-CO13-HEPAVIH cohort. Antiviral Ther. 2013.

  52. Pizzirusso M, Lin J, Head C, Marcus SM, Ahmed S, Brau N, et al. Impact of hepatitis C treatment initiation on adherence to concomitant medications. J Assoc Nurses AIDS Care. 2014;25(1):23–31.

    Article  PubMed  Google Scholar 

  53. Schneider MD, Sarrazin C. Antiviral therapy of hepatitis C in 2014: do we need resistance testing? Antiviral Res. 2014;105:64–71.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

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Conflict of interest

Kian Bichoupan is a paid consultant of Kadmon, Gilead Sciences, and Janssen Pharmaceuticals.

Dr. Douglas T. Dieterich serves as a paid lecturer and consultant, and is a member on scientific advisory boards of companies that either develop or assess medicines used for the treatment of viral hepatitis. These companies include Bristol-Myers Squibb, Gilead Sciences, Boehringer Ingelheim, Idenix, Merck, and Janssen Pharmaceuticals.

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Bichoupan, K., Dieterich, D.T. Hepatitis C in HIV-Infected Patients: Impact of Direct-Acting Antivirals. Drugs 74, 951–961 (2014). https://doi.org/10.1007/s40265-014-0232-6

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