Skip to main content

Advertisement

SpringerLink
Log in

HIV-Hepatitis C Virus Co-infection in the era of Direct-Acting Antivirals

  • Co-infections and Comorbidity (CM Wyatt and K Sigel, Section Editors)
  • Published:
Current HIV/AIDS Reports Aims and scope Submit manuscript

Abstract

Approximately one-third of patients infected with human immunodeficiency virus (HIV) are concomitantly infected with hepatitis C virus (HCV). As a result, liver disease remains a major source of morbidity and mortality in HIV patients. Prior to 2011, treatments of HCV lacked efficacy in clinical trials in HIV/HCV co-infected patients. Fortunately, several direct-acting antivirals (DAAs) have now entered clinical practice and others have reached advanced stages of clinical development. These therapies offer significant benefits such as improved rates of sustained virologic response (SVR), shortened durations of treatment, and compatibility with HIV antiretroviral therapies. Treatments such as sofosbuvir (SOF) have received approval for HIV/HCV co-infected patients. Moreover, interferon-free options exist for HIV/HCV co-infected patients who may be ineligible or intolerant of interferon. Despite these improvements, physicians must be aware of the differences between these DAAs, the patient characteristics that play a role on the effectiveness of these medications, and the drug-drug interactions these DAAs may have with existing HIV antiretroviral therapies. The aim of this review is to discuss the prevalence and incidence of HIV/HCV co-infection, critical factors related to patient evaluation, current treatment options, and new developments in the management of HIV/HCV co-infected patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hernando V, Perez-Cachafeiro S, Lewden C, Gonzalez J, Segura F, Oteo JA, et al. All-cause and liver-related mortality in HIV positive subjects compared to the general population: differences by HCV co-infection. J Hepatol. 2012;57(4):743–51.

    Article  PubMed  Google Scholar 

  2. Qurishi N, Kreuzberg C, Luchters G, Effenberger W, Kupfer B, Sauerbruch T, et al. Effect of antiretroviral therapy on liver-related mortality in patients with HIV and hepatitis C virus coinfection. Lancet. 2003;362(9397):1708–13.

    Article  CAS  PubMed  Google Scholar 

  3. Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138(2):513–21. 21 e1-6.

    Article  PubMed  Google Scholar 

  4. Buti M, San Miguel R, Brosa M, Cabases JM, Medina M, Angel Casado M, et al. Estimating the impact of hepatitis C virus therapy on future liver-related morbidity, mortality and costs related to chronic hepatitis C. J Hepatol. 2005;42(5):639–45.

    Article  PubMed  Google Scholar 

  5. Dieperink E, Pocha C, Thuras P, Knott A, Colton S, Ho SB. All-cause mortality and liver-related outcomes following successful antiviral treatment for chronic hepatitis C. Dig Dis Sci. 2014;59(4):872–80.

    Article  CAS  PubMed  Google Scholar 

  6. Backus LI, Boothroyd DB, Phillips BR, Belperio P, Halloran J, Mole LA. A sustained virologic response reduces risk of all-cause mortality in patients with hepatitis C. Clin Gastroenterol Hepatol : Off Clin Pract J Am Gastroenterol Assoc. 2011;9(6):509–16.

    Article  Google Scholar 

  7. 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 : J Am Med Assoc. 2012;308(24):2584–93.

    Article  Google Scholar 

  8. Nunez M, Miralles C, Berdun MA, Losada E, Aguirrebengoa K, Ocampo A, 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 Retrovir. 2007;23(8):972–82.

    Article  CAS  PubMed  Google Scholar 

  9. 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 Central  PubMed  Google Scholar 

  10. 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 

  11. 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 : J Am Med Assoc. 2004;292(23):2839–48.

    Article  CAS  Google Scholar 

  12. 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.

    Article  CAS  PubMed  Google Scholar 

  13. Ioannou G, Scott JD, Yang Y, Green PK, Beste LA. Rates and predictors of response to anti-viral treatment for hepatitis C virus in HIV/HCV co-infection in a nationwide study of 619 patients. Aliment Pharmacol Ther. 2013;38(11–12):1373–84.

  14. Urbanus AT, van de Laar TJ, Stolte IG, Schinkel J, Heijman T, Coutinho RA, et al. Hepatitis C virus infections among HIV-infected men who have sex with men: an expanding epidemic. AIDS. 2009;23(12):F1–7.

    Article  PubMed  Google Scholar 

  15. Boceprevir package insert. [cited 2013 December 30]; Available from:http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202258lbl.pdf.

  16. Pearlman BL. Protease inhibitors for the treatment of chronic hepatitis C genotype-1 infection: the new standard of care. Lancet Infect Dis. 2012;12(9):717–28.

    Article  CAS  PubMed  Google Scholar 

  17. Sofosbuvir package insert. [cited 2013 December 30]; Available from:http://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/sovaldi/sovaldi_pi.pdf.

  18. Ghany MG, Strader DB, Thomas DL, Seeff LB. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49(4):1335–74.

    Article  CAS  PubMed  Google Scholar 

  19. Bottieau E, Apers L, Van Esbroeck M, Vandenbruaene M, Florence E. Hepatitis C virus infection in HIV-infected men who have sex with men: sustained rising incidence in Antwerp, Belgium, 2001-2009. Euro surveillance : bulletin Europeen sur les maladies transmissibles =. Eur Commun Dis Bull. 2010;15(39):19673.

    CAS  Google Scholar 

  20. van der Helm JJ, Prins M, del Amo J, Bucher HC, Chene G, Dorrucci M, et al. The hepatitis C epidemic among HIV-positive MSM: incidence estimates from 1990 to 2007. AIDS. 2011;25(8):1083–91.

    Article  PubMed  Google Scholar 

  21. Centers for Disease C. Prevention. Sexual transmission of hepatitis C virus among HIV-infected men who have sex with men--New York City, 2005-2010. MMWR Morb Mortal Wkly Rep. 2011;60(28):945–50.

    Google Scholar 

  22. Rauch A, Rickenbach M, Weber R, Hirschel B, Tarr PE, Bucher HC, 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 : Off Publ Infect Dis Soc Am. 2005;41(3):395–402.

    Article  Google Scholar 

  23. Lambers FA, Prins M, Thomas X, Molenkamp R, Kwa D, Brinkman K, et al. Alarming incidence of hepatitis C virus re-infection after treatment of sexually acquired acute hepatitis C virus infection in HIV-infected MSM. AIDS. 2011;25(17):F21–7.

    Article  PubMed  Google Scholar 

  24. Martin TC, Martin NK, Hickman M, Vickerman P, Page EE, Everett R, et al. Hepatitis C virus reinfection incidence and treatment outcome among HIV-positive MSM. AIDS. 2013;27(16):2551–7.

    Article  PubMed  Google Scholar 

  25. Ingiliz P, Krznaric I, Stellbrink HJ, Knecht G, Lutz T, Noah C, et al. Multiple hepatitis C virus (HCV) reinfections in HIV-positive men who have sex with men: no influence of HCV genotype switch or interleukin-28B genotype on spontaneous clearance. HIV Med. 2014. doi:10.1111/hiv.12127.

    PubMed  Google Scholar 

  26. Al-Mohri H, Murphy T, Lu Y, Lalonde RG, Klein MB. Evaluating liver fibrosis progression and the impact of antiretroviral therapy in HIV and hepatitis C coinfection using a noninvasive marker. J Acquir Immune Defic Syndr. 2007;44(4):463–9.

    Article  PubMed  Google Scholar 

  27. Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43(6):1317–25.

    Article  CAS  PubMed  Google Scholar 

  28. Bruix J, Sherman M. Management of Hepatocellular Carcinoma: An Update. Available from: http://www.aasld.org/practiceguidelines/Documents/Bookmarked Practice Guidelines/HCCUpdate2010.pdf.

  29. Garcia-Tsao G, Sanyal A, Grace N, Carey W. Prevention and Management of Gastroesophageal Varices and Variceal Hemorrhage in Cirrhosis. Available from: http://www.aasld.org/practiceguidelines/Documents/Bookmarked Practice Guidelines/Prevention and Management of Gastro Varices and Hemorrhage.pdf.

  30. Martel-Laferriere V, Dieterich DT. Treating HCV in HIV 2013: on the cusp of change. Liver Int : Off J Int Assoc Study Liver. 2014;34 Suppl 1:53–9.

    Article  CAS  Google Scholar 

  31. 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 

  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.

  33. Naggie S, Sulkowski M, Lalezari J, Fessel WJ, Mounzer K, Shuhart MC, et al. All-Oral Therapy With Sofosbuvir Plus Ribavirin For the Treatment of HCV Genotype 1, 2, 3 Infection in Patients Co-infected With HIV (PHOTON-1). 21th Conference on Retroviruses and Opportunistic Infections, Boston, USA. March 2014.

  34. Martel-Laferriere V, Brinkley S, Bichoupan K, Posner S, Stivala A, Perumalswami P, et al. Virological response rates for telaprevir-based hepatitis C triple therapy in patients with and without HIV coinfection. HIV Med. 2013. doi:10.1111/hiv.12086.

    PubMed  Google Scholar 

  35. 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(3):744–53.e3.

  36. 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 

  37. 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 Nov 1-5 2013.

  38. Cotte L, Vincent C, Sogni P, Fournier I, Aumaitre H, De Truchis P, et al. Telaprevir in Treatment-Experienced HIV-HCV G1 Coinfected Patients (ANRS HC26 TelapreVIH) 21st Conference on Retroviruses and Opportunistic Infections; Bosto, MA March 3-6, 20142014.

  39. Neukam K, Munteanu D, Rivero A, Haberl A, Marquez M, Ingiliz P, et al. Boceprevir/Telaprevir-Based Therapy in HIV-Infection: Interim Analysis of a Multicenter Cohort 21st Conference on Retroviruses and Opportunistic Infections; Bosto, MA March 3-6, 20142014.

  40. Gori A, Doroana M, Chernova O, Rockstroh J, Banhegyi D, Bergin C, et al. Telaprevir Treatment of HIV/HCV G1 Patients With Severe Fibrosis: Efficacy Results To Week 16. 21th Conference on Retroviruses and Opportunistic Infections, Boston, USA March 2014.

  41. Cotte L, Barrail-Tran A, Vincent C, Valantin M, Fournier I, Lacombe K, et al. Telaprevir Increases Ribavirin Toxicity Through eGFR Decrease in HIV-HCV Coinfected Patients 21st Conference on Retroviruses and Opportunistic Infections; Bosto, MA March 3-6, 20142014.

  42. Poizot-Martin I, Bellissant E, Colson P, Renault A, Piroth L, Solas C, et al. Boceprevir for Previously Treated HCV-HIV Coinfected Patients: The ANRS-HC27 BocepreVIH Trial 21th Conference on Retroviruses and Opportunistic Infections, Boston, USA March 2014.

  43. Rodriguez-Torres M, Rodriguez-Orgengo J, Gaggar A, Shen G, Symonds B, McHutchison J, et al. Infectious Disease Week October 2-6, 2013; San Francisco.

  44. Hagan LM, Sulkowski MS, Schinazi RF. Cost analysis of sofosbuvir/ribavirin versus sofosbuvir/simeprevir for genotype 1 hepatitis C virus in interferon-ineligible/intolerant individuals. Hepatology. 2014;60(1):37–45.

  45. Jacobson I, Ghalib R, Rodriguez-Torres M, Younossi Z, Corregidor A, Sulkowski 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 64th Annual Meeting of the AMerican Association for th Study of Liver Diseases; Washington, DC Nov 1-5 2013

  46. Lawitz E, Hezode C, Gane E, Tam E, Lagging M, Balart L, et al. Efficacy and safety of MK-5172 and MK-8742 ± RIBAVIRIN IN Hepatitis C Genotype 1 Infected Patients with cirrhosis or previous null response: the C-WORTHY Study. EASL - The International Liver Congress 2014 49th Annual Meeting of the European Association for the Sudy of the Liver; London, United Kingdom April 9-13.

  47. Kowdley KV, Lawitz E, Poordad F, Cohen DE, Nelson DR, Zeuzem S, et al. Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1. N Engl J Med. 2014;370(3):222–32.

    Article  CAS  PubMed  Google Scholar 

  48. Kohli A, Sims Z, Miriam M, Nelson A, Osinusi A, Bon D, et al. Combination Oral, Hepatitis C Antiviral Therapy for 6 or 12 Weeks: Results of the SYNERGY Trial 21st Conference on Retroviruses and Opportunistic Infections; Boston, MA March 3-6, 2014.

  49. Hezode C, Bruno S, Jacobson I, Serfaty L, Kwo P, Zhou A, et al. Safety and Efficacy of MK-5172 Plus Peginterferon Alfa-2b and Ribavirin (PR) in Cirrhotic and Noncirrhotic Treatment-Naive Patients With Hepatitis C Virus (HCV) Genotype (G)1 Infection EASL - The International Liver Congress 2014 49th Annual Meeting of the European Association for the Study of the Liver; London, United Kingdom April 9-13.

Download references

Compliance with Ethics Guidelines

ᅟ

Conflict of Interest

Kian Bichoupan reports personal fees from Gilead, personal fees from Janssen for outside the submitted work.

Douglas T. Dieterich reports personal fees from BMS, personal fees from Gilead, personal fees from BI, personal fees from Idenix, personal fees from Merck, personal fees from Janssen for outside the submitted work.

Valérie Martel-Laferrière declares that she has no conflict 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.

Author information

Authors and Affiliations

  1. Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY, USA

    Kian Bichoupan

  2. Division of Liver Disease, Icahn School of Medicine at Mount Sinai, 1468 Madison Ave, Annenberg 21-42, New York, NY, USA

    Douglas T. Dieterich

  3. Département de Microbiologie et Infectiologie, Centre Hospitalier de l′Université de Montréal, Montréal, QC, Canada

    Valérie Martel-Laferrière

Authors
  1. Kian Bichoupan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Douglas T. Dieterich
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Valérie Martel-Laferrière
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kian Bichoupan.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bichoupan, K., Dieterich, D.T. & Martel-Laferrière, V. HIV-Hepatitis C Virus Co-infection in the era of Direct-Acting Antivirals. Curr HIV/AIDS Rep 11, 241–249 (2014). https://doi.org/10.1007/s11904-014-0217-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11904-014-0217-9

Keywords

Search

Navigation