Advertisement

Current Treatment Options in Infectious Diseases

, Volume 8, Issue 4, pp 379–399 | Cite as

Hepatitis C Treatment in HIV Coinfection: Approaches, Challenges, and Future Opportunities

  • Autumn Bagwell
  • Cody A. ChastainEmail author
Hepatitis C (K Marks, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Hepatitis C

Opinion statement

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection is a significant cause of morbidity and mortality in people living with HIV/AIDS. Indeed, HCV is more likely to progress to end-organ dysfunction in HIV-infected people, and fibrosis progresses more quickly in this population than in the general population. While historical treatments combining interferon and ribavirin were less efficacious in HIV/HCV coinfection, modern direct-acting antiviral (DAA) therapies have shown similar clinical efficacy in HIV/HCV coinfection as in HCV monoinfection. In light of these findings, HIV/HCV-coinfected patients may benefit even more from new HCV treatment approaches. The choice of DAA therapy for HCV in HIV-infected patients should be based on the patient’s disease stage, prior treatment history, and viral characteristics such as genotype and/or resistance mutations, just as it is in patients with HCV monoinfection. Potential drug-drug interactions between HIV antiretroviral therapy (ART) and HCV DAA therapy must be considered when prescribing HCV treatment and may impact the choice of treatment. Caution is advised when considering DAA regimens that have not been studied in HIV/HCV populations due to lack of data regarding efficacy, the potential for drug-drug interactions, or both. In the era of DAA therapy and with many therapeutic options available to tailor appropriate regimens in order to avoid drug-drug interactions, HCV should be treated aggressively in HIV-infected persons to reduce morbidity and mortality.

Keywords

Hepatitis C virus HCV Human immunodeficiency virus HIV Coinfection 

Notes

Compliance with Ethical Standards

Conflict of Interest

Dr. Autumn Bagwell declares that she has no conflicts of interest.

Dr. Cody A. Chastain declares that he has no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology. 2013;57(4):1333–42. doi: 10.1002/hep.26141.CrossRefPubMedGoogle Scholar
  2. 2.
    Stanaway JD, Flaxman AD, Naghavi M, Fitzmaurice C, Vos T, Abubakar I, et al. The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013. Lancet. 2016. doi: 10.1016/S0140-6736(16)30579-7.Google Scholar
  3. 3.
    Denniston MM, Jiles RB, Drobeniuc J, Klevens RM, Ward JW, McQuillan GM, et al. Chronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010. Ann Intern Med. 2014;160(5):293–300. doi: 10.7326/M13-1133.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Ditah I, Ditah F, Devaki P, Ewelukwa O, Ditah C, Njei B, et al. The changing epidemiology of hepatitis C virus infection in the United States: National Health and Nutrition Examination Survey 2001 through 2010. J Hepatol. 2014;60(4):691–8. doi: 10.1016/j.jhep.2013.11.014.CrossRefPubMedGoogle Scholar
  5. 5.
    Chak E, Talal AH, Sherman KE, Schiff ER, Saab S. Hepatitis C virus infection in USA: an estimate of true prevalence. Liver Int. 2011;31(8):1090–101. doi: 10.1111/j.1478-3231.2011.02494.x.CrossRefPubMedGoogle Scholar
  6. 6.•
    Ly KN, Hughes EM, Jiles RB, Holmberg SD. Rising mortality associated with hepatitis C virus in the United States, 2003-2013. Clin Infect Dis. 2016;62(10):1287–8. doi: 10.1093/cid/ciw111. This study demonstrated that from 2003-2013, HCV-associated mortality was greater than 60 other nationally reportable infectious conditions combined.
  7. 7.
    Alter MJ. Epidemiology of viral hepatitis and HIV co-infection. J Hepatol. 2006;44(1 Suppl):S6–9. doi: 10.1016/j.jhep.2005.11.004.CrossRefPubMedGoogle Scholar
  8. 8.
    Raymond HF, Hughes A, O’Keefe K, Stall RD, McFarland W. Hepatitis C prevalence among HIV-positive MSM in San Francisco: 2004 and 2008. Sex Transm Dis. 2011;38(3):219–20. doi: 10.1097/OLQ.0b013e3181f68ed4.CrossRefPubMedGoogle Scholar
  9. 9.
    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(6):831–7. doi: 10.1086/339042.CrossRefPubMedGoogle Scholar
  10. 10.
    Frederick T, Burian P, Terrault N, Cohen M, Augenbraun M, Young M, et al. Factors associated with prevalent hepatitis C infection among HIV-infected women with no reported history of injection drug use: the Women’s Interagency HIV Study (WIHS). AIDS Patient Care STDs. 2009;23(11):915–23. doi: 10.1089/apc.2009.0111.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.•
    Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, et al. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet. 2014;384(9939):241–8. doi: 10.1016/S0140-6736(14)60604-8. This updated analysis of the D:A:D cohort revealed that liver disease was the third leading cause of death in people with HIV.
  12. 12.•
    Farahani M, Mulinder H, Farahani A, Marlink R. Prevalence and distribution of non-AIDS causes of death among HIV-infected individuals receiving antiretroviral therapy: a systematic review and meta-analysis. Int J STD AIDS. 2016. doi: 10.1177/0956462416632428. This systematic review and meta-analysis of 19 studies revealed liver disease as a leading cause of death among people living with HIV.
  13. 13.•
    Trickey A, May MT, Vehreschild J, Obel N, Gill MJ, Crane H, et al. Cause-specific mortality in HIV-positive patients who survived ten years after starting antiretroviral therapy. PLoS One. 2016;11(8):e0160460. doi: 10.1371/journal.pone.0160460. Liver-related disease was identified as a leading cause of death in the Antiretroviral Therapy Cohort Collaboration (ART-CC).
  14. 14.
    Graham CS, Baden LR, Yu E, Mrus JM, Carnie J, Heeren T, et al. Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis. Clin Infect Dis. 2001;33(4):562–9. doi: 10.1086/321909.CrossRefPubMedGoogle Scholar
  15. 15.
    Kirk GD, Mehta SH, Astemborski J, Galai N, Washington J, Higgins Y, et al. HIV, age, and the severity of hepatitis C virus-related liver disease: a cohort study. Ann Intern Med. 2013;158(9):658–66. doi: 10.7326/0003-4819-158-9-201305070-00604.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Pineda JA, Garcia-Garcia JA, Aguilar-Guisado M, Rios-Villegas MJ, Ruiz-Morales J, Rivero A, et al. Clinical progression of hepatitis C virus-related chronic liver disease in human immunodeficiency virus-infected patients undergoing highly active antiretroviral therapy. Hepatology. 2007;46(3):622–30. doi: 10.1002/hep.21757.CrossRefPubMedGoogle Scholar
  17. 17.
    Thein HH, Yi Q, Dore GJ, Krahn MD. 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. 2008;22(15):1979–91. doi: 10.1097/QAD.0b013e32830e6d51.CrossRefPubMedGoogle Scholar
  18. 18.
    Sulkowski MS, Mehta SH, Torbenson MS, Higgins Y, Brinkley SC, de Oca RM, et al. Rapid fibrosis progression among HIV/hepatitis C virus-co-infected adults. AIDS. 2007;21(16):2209–16. doi: 10.1097/QAD.0b013e3282f10de9.CrossRefPubMedGoogle Scholar
  19. 19.
    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. doi: 10.1056/NEJMoa032653.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    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. doi: 10.1056/NEJMoa040842.CrossRefPubMedGoogle Scholar
  21. 21.
    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. doi: 10.1001/jama.292.23.2839.CrossRefPubMedGoogle Scholar
  22. 22.
    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. doi: 10.1016/S1473-3099(13)70149-X.CrossRefPubMedGoogle Scholar
  23. 23.
    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. doi: 10.7326/0003-4819-159-2-201307160-00654.PubMedGoogle Scholar
  24. 24.
    Wyles DL, Sulkowski MS, Dieterich D. Management of Hepatitis C/HIV coinfection in the era of highly effective hepatitis C virus direct-acting antiviral therapy. Clin Infect Dis. 2016;63(Suppl 1):S3–S11. doi: 10.1093/cid/ciw219.CrossRefPubMedGoogle Scholar
  25. 25.
    Webster DP, Klenerman P, GM D. Hepatitis C. Lancet. 2015;385(9973):1124–35. doi: 10.1016/S0140-6736(14)62401-6.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Li HC, Lo SY. Hepatitis C virus: virology, diagnosis and treatment. World J Hepatol. 2015;7(10):1377–89. doi: 10.4254/wjh.v7.i10.1377.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Scheel TK, Rice CM. Understanding the hepatitis C virus life cycle paves the way for highly effective therapies. Nat Med. 2013;19(7):837–49. doi: 10.1038/nm.3248.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Gentile I, Maraolo AE, Buonomo AR, Zappulo E, Borgia G. The discovery of sofosbuvir: a revolution for therapy of chronic hepatitis C. Expert Opin Drug Discov. 2015;10(12):1363–77. doi: 10.1517/17460441.2015.1094051.CrossRefPubMedGoogle Scholar
  29. 29.•
    Rodriguez-Torres M, Gaggar A, Shen G, Kirby B, Svarovskaia E, Brainard D, et al. Sofosbuvir for chronic hepatitis C virus infection genotype 1-4 in patients coinfected with HIV. J Acquir Immune Defic Syndr. 2015;68(5):543–9. doi: 10.1097/QAI.0000000000000516. This small study demonstrated no clinically significant drug-drug interaction between sofosbuvir and multiple antiretrovirals. It also demonstrated high efficacy of sofosbuvir in combination with pegylated interferon and ribavirin.
  30. 30.
    Hundemer GL, Sise ME, Wisocky J, Ufere N, Friedman LS, Corey KE, et al. Use of sofosbuvir-based direct-acting antiviral therapy for hepatitis C viral infection in patients with severe renal insufficiency. Infect Dis (Lond). 2015;47(12):924–9. doi: 10.3109/23744235.2015.1078908.CrossRefGoogle Scholar
  31. 31.
    Kirby BJ, Symonds WT, Kearney BP, Mathias AA. Pharmacokinetic, Pharmacodynamic, and drug-interaction profile of the hepatitis C virus NS5B polymerase inhibitor sofosbuvir. Clin Pharmacokinet. 2015;54(7):677–90. doi: 10.1007/s40262-015-0261-7.CrossRefPubMedGoogle Scholar
  32. 32.
    Harvoni (R) [package insert]. Gilead Sciences I, Foster City, CA; 2014.Google Scholar
  33. 33.
    FDA Drug Safety Communication: FDA warns of serious slowing of the heart rate when antiarrhythmic drug amiodarone is used with hepatitis C treatments containing sofosbuvir (Harvoni) or Sovaldi in combination with another direct acting antiviral drug. 2015.Google Scholar
  34. 34.••
    Osinusi A, Townsend K, Kohli A, et al. Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV co-infection. JAMA. 2015;313(12):1232–9. doi: 10.1001/jama.2015.1373. This phase 2b, open-label, single-center study conducted at the National Institutes of Health reported high efficacy of ledipasvir/sofosbuvir in HIV/HCV coinfected patients.
  35. 35.••
    Naggie S, Cooper C, Saag M, Workowski K, Ruane P, Towner WJ, et al. Ledipasvir and sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):705–13. doi: 10.1056/NEJMoa1501315. This multicenter, open-label study reported high efficacy of ledipasvir/sofosbuvir in HIV/HCV co-infected patients. It remains one of the largest studies of direct acting antivirals conducted to date in HIV/HCV co-infected patients.
  36. 36.
    Kowdley KV, Gordon SC, Reddy KR, Rossaro L, Bernstein DE, Lawitz E, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370(20):1879–88. doi: 10.1056/NEJMoa1402355.
  37. 37.•
    AASLD-IDSA. Initial treatment of HCV infection. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org/full-report/hcv-testing-and-linkage-care. Accessed September 20, 2016. The AASLD-IDSA HCV Guidance provides recommendations for testing, managing, and treating HCV and is regularly reviewed and updated. This section discusses initial treatment of HCV.
  38. 38.•
    Ingiliz P, Christensen S, Kimhofer T, Hueppe D, Lutz T, Schewe K, et al. Sofosbuvir and ledipasvir for 8 weeks for the treatment of chronic hepatitis C virus infection in HCV-mono-infected and HIV-HCV co-infected individuals—results from the German hepatitis C cohort (GECCO-01). Clin Infect Dis. 2016. doi: 10.1093/cid/ciw567. This real-world German cohort demonstrated high efficacy of eight weeks of ledipasvir and sofosbuvir in selected HCV mono-infected and HIV/HCV co-infected patients.
  39. 39.
    Guedj J, Dahari H, Rong L, Sansone ND, Nettles RE, Cotler SJ, et al. Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life. Proc Natl Acad Sci U S A. 2013;110(10):3991–6. doi: 10.1073/pnas.1203110110.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Adler H, Lambert JS. Daclatasvir for the treatment of hepatitis C virus infection. Expert Rev Gastroenterol Hepatol. 2014;8(7):725–38. doi: 10.1586/17474124.2014.925798.CrossRefPubMedGoogle Scholar
  41. 41.
    Daklinza (R) [package insert]. Bristol-Myers Squibb. Princeton N.Google Scholar
  42. 42.•
    AASLD-IDSA. Monitoring patients who are starting hepatitis C treatment, are on treatment, or have completed therapy. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org/full-report/hcv-testing-and-linkage-care. Accessed September 20, 2016. The AASLD-IDSA HCV Guidance provides recommendations for testing, managing, and treating HCV and is regularly reviewed and updated. This section discusses the monitoring of patients with HCV.
  43. 43.
    Bifano M, Hwang C, Oosterhuis B, Hartstra J, Grasela D, Tiessen R, et al. Assessment of pharmacokinetic interactions of the HCV NS5A replication complex inhibitor daclatasvir with antiretroviral agents: ritonavir-boosted atazanavir, efavirenz and tenofovir. Antivir Ther. 2013;18(7):931–40. doi: 10.3851/IMP2674.CrossRefPubMedGoogle Scholar
  44. 44.••
    Wyles DL, Ruane PJ, Sulkowski MS, Dieterich D, Luetkemeyer A, Morgan TR, et al. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):714–25. doi: 10.1056/NEJMoa1503153. This open-label study revealed high efficacy of daclatasvir and sofosbuvir when prescribed for 12 weeks in HIV/HCV-coinfected patients.
  45. 45.
    Epclusa (R) [package insert]. Gilead Sciences IFC, CA; 2016.Google Scholar
  46. 46.
    Cheng G Ty YM, Lee Y-J, Gong R, Trejo-Martin A, Peng B, Robinson M, Beran R, Bush C, Chan K, Nash M, Worth A, Yang H, Perry J, Tyalor J, Yang C, Paulson M, Delaney W, Link JO. GS-5816, a second generation HCV NS5A inhibitor with potent antiviral activity, broad genotypic coverage and a high resistance barrier 48th Annual Meeting of the European Association for the Study of the Liver. 2013.Google Scholar
  47. 47.
    Younossi ZM, Stepanova M, Feld J, Zeuzem S, Jacobson I, Agarwal K, et al. Sofosbuvir/velpatasvir improves patient-reported outcomes in HCV patients: results from ASTRAL-1 placebo-controlled trial. J Hepatol. 2016;65(1):33–9. doi: 10.1016/j.jhep.2016.02.042.CrossRefPubMedGoogle Scholar
  48. 48.
    Foster GR, Afdhal N, Roberts SK, Brau N, Gane EJ, Pianko S, et al. Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Engl J Med. 2015;373(27):2608–17. doi: 10.1056/NEJMoa1512612.CrossRefPubMedGoogle Scholar
  49. 49.
    Mogalian E SL, Osinusi A, Shen G, Sajwani K, McNally J, Ling J, Mathias A. Drug-drug interaction studies between hepatitis C virus antivirals sofosbuvir and velpatasvir, and HIV antiretroviral therapies. 66th Annual Meeting of the American Association for the Study of Liver Diseases, San Francisco, CA, November 13–17, 2015.Google Scholar
  50. 50.•
    AASLD-IDSA. Unique patient populations: patients with HIV/HCV coinfection. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org/full-report/hcv-testing-and-linkage-care. Accessed September 20, 2016. The AASLD-IDSA HCV Guidance provides recommendations for testing, managing, and treating HCV and is regularly reviewed and updated. This section discusses treatment of HIV/HCV coinfection.
  51. 51.•
    Wyles D, Brau N, Kottilil S et al. Sofosbuvir/velpatasvir for 12 weeks in patients coinfected with HCV and HIV-1: the ASTRAL-5 Study. European Association for the Study of the Liver Barcelona, Spain, April 13–17, 2016. This recent study reported high efficacy of sofosbuvir/velpatasvir in HIV/HCV-coinfected patients.Google Scholar
  52. 52.
    Menon RM, Klein CE, Podsadecki TJ, Chiu YL, Dutta S, Awni WM. Pharmacokinetics and tolerability of paritaprevir, a direct acting antiviral agent for hepatitis C virus treatment, with and without ritonavir in healthy volunteers. Br J Clin Pharmacol. 2016;81(5):929–40. doi: 10.1111/bcp.12873.CrossRefPubMedGoogle Scholar
  53. 53.
    Stirnimann G. Ombitasvir (ABT-267), a novel NS5A inhibitor for the treatment of hepatitis C. Expert Opin Pharmacother. 2014;15(17):2609–22. doi: 10.1517/14656566.2014.972364.CrossRefPubMedGoogle Scholar
  54. 54.
    Trivella JP, Gutierrez J, Martin P. Dasabuvir : a new direct antiviral agent for the treatment of hepatitis C. Expert Opin Pharmacother. 2015;16(4):617–24. doi: 10.1517/14656566.2015.1012493.CrossRefPubMedGoogle Scholar
  55. 55.
    Viekira Pak (R) [package insert]. AbbVie Inc. NC, IL; 2014.Google Scholar
  56. 56.
    Technivie (R) [package insert]. AbbVie Inc. NC, IL; 2015.Google Scholar
  57. 57.
    Khatri A, Dutta S, Wang H, Podsadecki T, Trinh R, Awni W, et al. Evaluation of drug-drug interactions between hepatitis C antiviral agents ombitasvir, paritaprevir/ritonavir, and dasabuvir and HIV-1 protease inhibitors. Clin Infect Dis. 2016;62(8):972–9. doi: 10.1093/cid/civ1213.CrossRefPubMedGoogle Scholar
  58. 58.
    Sollima S, D’Avolio A, Cattaneo D, Micheli V, Milazzo L, Gervasoni C. Darunavir-based antiretroviral therapy may affect the efficacy of ombitasvir/paritaprevir/ritonavir and dasabuvir in HCV/HIV-1 coinfected patients. Clin Infect Dis. 2016;63(2):285–6. doi: 10.1093/cid/ciw292.CrossRefPubMedGoogle Scholar
  59. 59.
    Wyles D, Trinh R, Lalezari J, Adeyemi O, Bhatti L, Khatri A, King JR, Hu YB, Viani R, Shulman NS, Ruane P. TURQUOISE-I part 1b: ombitasvir/paritaprevir/r + dasabuvir + RBV for HCV/HIV coinfection. Conference on Retroviruses and Opportunistic Infections; Boston, Massachusetts, 2016.Google Scholar
  60. 60.
    Hep Drug Interactions. The University of Liverpool. 2016. http://www.hep-druginteractions.org/checker. Accessed July 30th 2016.
  61. 61.
    Poordad F, Bennett M, Sepe TE, et al. Retreatment of HCV genotype 1 DAA-failures with ombitasvir/paritaprevir/r, dasabuvir, and sofosbuvir. Hepatology. 2015;62(6):–1392A.Google Scholar
  62. 62.
    Pockros PJ, Reddy KR, Mantry PS, Cohen E, Bennett M, Sulkowski MS, et al. LO1: safety of ombitasvir/paritaprevir/ritonavir plus dasabuvir for treating HCV GT1 infection in patients with severe renal impairment or end-stage renal disease: the RUBY-I study. J Hepatol. 2015;62:S257. doi: 10.1016/S0168-8278(15)30147-1.CrossRefGoogle Scholar
  63. 63.••
    Sulkowski MS, Eron JJ, Wyles D, Trinh R, Lalezari J, Wang C, et al. Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial. JAMA. 2015;313(12):1223–31. doi: 10.1001/jama.2015.1328. This randomized, open-label study reported high efficacy of PrOD plus ribavirin in HIV/HCV-coinfected patients.
  64. 64.
    Hezode C, Asselah T, Reddy KR, Hassanein T, Berenguer M, Fleischer-Stepniewska K, et al. Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naive and treatment-experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I): a randomised, open-label trial. Lancet. 2015;385(9986):2502–9. doi: 10.1016/S0140-6736(15)60159-3.CrossRefPubMedGoogle Scholar
  65. 65.
    Alric L, Bonnet D. Grazoprevir + elbasvir for the treatment of hepatitis C virus infection. Expert Opin Pharmacother. 2016;17(5):735–42. doi: 10.1517/14656566.2016.1161028.CrossRefPubMedGoogle Scholar
  66. 66.
    Lahser F, Liu R, Bystol K, Xia E, Raubertas R, Asante-Appiah E, et al. A combination containing MK-5172 (HCV NS3 protease inhibitor) and MK-8742 (HCV NS5A inhibitor) demonstrates high barrier to resistance in vitro in HCV replicons. Hepatology. 2012;56(suppl S1):236A.Google Scholar
  67. 67.
    Flamm SL. Efficacy and safety of grazoprevir and elbasvir in hepatitis C genotype 1–infected patients with Child-Pugh class B cirrhosis (C-SALT Part A). Advances in the Treatment of Hepatitis C Virus Infection From EASL 2015. 2015;11(6):10.Google Scholar
  68. 68.
    Roth D, Nelson DR, Bruchfeld A, Liapakis A, Silva M, Monsour Jr H, et al. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4 & 5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. The Lancet. 386(10003):1537–45. doi: 10.1016/S0140–6736(15)00349-9.
  69. 69.
    Zepatier (R) [package insert]. Merck & Co. Inc. K, NJ; 2015Google Scholar
  70. 70.••
    Sulkowski M, Hezode C, Gerstoft J, Vierling JM, Mallolas J, Pol S, et al. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. Lancet. 2015;385(9973):1087–97. doi: 10.1016/S0140-6736(14)61793-1. This phase 2, multicenter, randomized controlled trial studied grazoprevir plus elbasvir with or without ribavirin in both HCV-monoinfected and HIV/HCV-coinfected patients. SVR rates were similar between each group.
  71. 71.••
    Rockstroh JK, Nelson M, Katlama C, Lalezari J, Mallolas J, Bloch M, et al. Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial. Lancet HIV. 2015;2(8):e319–27. doi: 10.1016/S2352-3018(15)00114-9. This phase 3, nonrandomized, open-label, single-arm study demonstrated high efficacy of grazoprevir plus elbasvir in HIV/HCV-coinfected patients.
  72. 72.•
    Dieterich D, Rockstroh JK, Orkin C, Gutierrez F, Klein MB, Reynes J, et al. Simeprevir (TMC435) with pegylated interferon/ribavirin in patients coinfected with HCV genotype 1 and HIV-1: a phase 3 study. Clin Infect Dis. 2014;59(11):1579–87. doi: 10.1093/cid/ciu675. This uncontrolled, open-label trial demonstrated excellent safety and high efficacy of simeprevir-based regimens in HIV/HCV coinfection.
  73. 73.•
    AASLD-IDSA. Retreatment of persons in whom prior therapy has failed. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org/full-report/hcv-testing-and-linkage-care. Accessed 20 Sept 2016. The AASLD-IDSA HCV Guidance provides recommendations for testing, managing, and treating HCV and is regularly reviewed and updated. This section discusses retreatment of HCV in persons who have previously failed therapy.
  74. 74.
    Olysio (R) [package insert]. Janssen Products L, Titusville, NJ; 2013.Google Scholar
  75. 75.•
    Del Bello D, Cha A, Sorbera M, Bichoupan K, Levine C, Doyle E, et al. Real-world sustained virologic response rates of sofosbuvir-containing regimens in patients coinfected with hepatitis C and HIV. Clin Infect Dis. 2016;62(12):1497–504. doi: 10.1093/cid/ciw119. This real-world, observational cohort study demonstrated the feasibility, safety, and efficacy of sofosbuvir-based regimens, including simeprevir plus sofosbuvir, in HIV/HCV-coinfected patients.
  76. 76.
    Pawlotsky JM, Feld JJ, Zeuzem S, Hoofnagle JH. From non-A, non-B hepatitis to hepatitis C virus cure. J Hepatol. 2015;62(1 Suppl):S87–99. doi: 10.1016/j.jhep.2015.02.006.CrossRefPubMedGoogle Scholar
  77. 77.•
    Sulkowski MS, Naggie S, Lalezari J, Fessel WJ, Mounzer K, Shuhart M, et al. Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection. JAMA. 2014;312(4):353–61. doi: 10.1001/jama.2014.7734. This phase 3, open-label, nonrandomized trial was conducted at 34 treatment centers and demonstrated high efficacy of sofosbuvir plus ribavirin in HIV/HCV-coinfected patients.
  78. 78.•
    Molina JM, Orkin C, Iser DM, Zamora FX, Nelson M, Stephan C, et al. Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV (PHOTON-2): a multicentre, open-label, non-randomised, phase 3 study. Lancet. 2015;385(9973):1098–106. doi: 10.1016/S0140-6736(14)62483-1. This phase 3, open-label, nonrandomized study was conducted at 45 sites and revealed high efficacy of sofosbuvir plus ribavirin in HIV/HCV-coinfected patients.
  79. 79.
    Ribavirin [package insert]. Aurobindo Pharma USA I, Dayton, NJ.Google Scholar
  80. 80.
    AbbVie. AbbVie presents new phase 2 data for investigational, once-daily, ribavirin-free, pan-genotypic regimen of ABT-493 and ABT-530 for hepatitis C genotypes 1–6. European Association for the Study of the Liver, Barcelona, Spain, April 13–17, 2016.Google Scholar
  81. 81.
    Asselah T, Boyer N, Saadoun D, Martinot-Peignoux M, Marcellin P. Direct-acting antivirals for the treatment of hepatitis C virus infection: optimizing current IFN-free treatment and future perspectives. Liver Int. 2016;36(Suppl 1):47–57. doi: 10.1111/liv.13027.CrossRefPubMedGoogle Scholar
  82. 82.
    Poordad F, Asatryan A, Felizarta F, Reindollar RW, Landis C, Fried MW, Bernstein DE, Ng TI, Lin C-W, Liu R, Kort J, Mensa FJ. High Efficacy of ABT-493 and ABT-530 in HCV genotype 1 infected patients who have failed direct-acting antiviral-containing regimens: the MAGELLAN-I Study. European Association for the Study of the Liver (EASL), Barcelona, Spain, April 13–17, 2016.Google Scholar
  83. 83.
    Lin CW, Asatryan A, Campbell A, Zhao W, Wang H, Sidhu D, Clifton II J, Kort J, Dutta S. Steady-state pharmacokinetics and safety of co-administration of pan-genotypic direct acting protease inhibitor ABT-493 with pan-genotypic NS5A inhibitor ABT-530 in healthy adult subjects. European Association for the Study of Liver Diseases, Vienna, Austria, April 22–26, 2015.Google Scholar
  84. 84.
    Gane E, Pianko S, Roberts SK, et al. Phase 2, randomized, open-label clinical trials of the efficacy and safety of grazoprevir and MK-3682 (NS5B polymerase inhibitor) with either elbasvir or MK-8408 (NS5A inhibitor) in patients with chronic HCV GT1, 2 or 3 infection (part a of C-CREST-1 & 2). San Francisco, CA: American Association for the Study of Liver Diseases; 2015.Google Scholar
  85. 85.
    Vernaz N, Girardin F, Goossens N, Brugger U, Riguzzi M, Perrier A, et al. Drug pricing evolution in hepatitis C. PLoS One. 2016;11(6):e0157098. doi: 10.1371/journal.pone.0157098.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Craxi L, Sacchini D, Refolo P, Minacori R, Daloiso V, Ricci G, et al. Prioritization of high-cost new drugs for HCV: making sustainability ethical. Eur Rev Med Pharmacol Sci. 2016;20(6):1044–51.PubMedGoogle Scholar
  87. 87.
    Rein DB, Wittenborn JS, Smith BD, Liffmann DK, Ward JW. The cost-effectiveness, health benefits, and financial costs of new antiviral treatments for hepatitis C virus. Clin Infect Dis. 2015;61(2):157–68. doi: 10.1093/cid/civ220.CrossRefPubMedGoogle Scholar
  88. 88.
    Bickerstaff C. The cost-effectiveness of novel direct acting antiviral agent therapies for the treatment of chronic hepatitis C. Expert Rev Pharmacoecon Outcomes Res. 2015;15(5):787–800. doi: 10.1586/14737167.2015.1076337.CrossRefPubMedGoogle Scholar
  89. 89.
    Younossi Z, Henry L. The impact of the new antiviral regimens on patient reported outcomes and health economics of patients with chronic hepatitis C. Dig Liver Dis. 2014;46(Suppl 5):S186–96. doi: 10.1016/j.dld.2014.09.025.CrossRefPubMedGoogle Scholar
  90. 90.
    Zhang S, Bastian ND, Griffin PM. Cost-effectiveness of sofosbuvir-based treatments for chronic hepatitis C in the US. BMC Gastroenterol. 2015;15:98. doi: 10.1186/s12876-015-0320-4.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Chahal HS, Marseille EA, Tice JA, Pearson SD, Ollendorf DA, Fox RK, et al. Cost-effectiveness of early treatment of hepatitis C virus genotype 1 by stage of liver fibrosis in a US treatment-naive population. JAMA Intern Med. 2016;176(1):65–73. doi: 10.1001/jamainternmed.2015.6011.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Pharmacy, Vanderbilt Specialty Pharmacy Vanderbilt University Medical CenterNashvilleUSA
  2. 2.Division of Infectious DiseasesVanderbilt University Medical CenterNashvilleUSA

Personalised recommendations