Advertisement

Digestive Diseases and Sciences

, Volume 63, Issue 11, pp 2829–2839 | Cite as

Similar Sustained Virologic Response in Real-World and Clinical Trial Studies of Hepatitis C/Human Immunodeficiency Virus Coinfection

  • Cameron Sikavi
  • Lisa Najarian
  • Sammy Saab
Review
  • 90 Downloads

Abstract

Background

Clinical trials evaluating efficacy of direct-acting antiviral (DAA) therapies demonstrate sustained virologic response (SVR) rates greater than 90% in patients infected with hepatitis C (HCV) and human immunodeficiency virus (HIV). However, generalizability of this data to real-world coinfected populations is unknown.

Aim

We aim to compare efficacy data from clinical trials to effectiveness data of real-world observational studies that evaluate oral interferon-free HCV treatment regimens in patients infected with HIV and HCV.

Methods

We included English-language studies on PubMed and MEDLINE databases from inception until October 2017. Eight clinical trials and 11 observational studies reporting on efficacy data and effectiveness data, respectively, of interferon-free oral DAA regimens in HCV/HIV coinfected patients, were included.

Results

Of patients in the eight clinical trials evaluated, 93.1% (1218/1308) achieved SVR12; of the 11 real-world observational studies, 90.8% (2269/2499) achieved SVR12. Relative risk between those treated in clinical trials versus observational studies was 0.98. Patients with genotype 1 infection, African-American patients, cirrhotic patients, and patients with prior HCV treatment experience had similar rates of SVR in real-world and clinical trial cohorts.

Conclusion

SVR among real-world HCV/HIV coinfected populations treated with DAA regimens is similar to SVR of patients studied in clinical trials. Historically negative predictors of achieving SVR during the era of interferon-based treatments, such as those with cirrhosis, prior HCV treatment failure, GT1 infection, and African-American race, are not associated with a significantly lower SVR in real-world populations treated with various DAA regimens.

Keywords

Hepatitis C HIV Coinfection Sustained virologic response 

Notes

Author’s contribution

Study concept and design (CS, SS); acquisition of data (CS, LN); analysis and interpretation of data (CS); drafting of the manuscript (CS, LN); critical revision of the manuscript for important intellectual content (SS); statistical analysis (not applicable; administrative, technical, or material support; study supervision (SS).

Funding

None.

Compliance with ethical standards

Conflict of interest

The authors of this manuscript have no conflicts of interest to disclose.

References

  1. 1.
    Platt L, Easterbrook P, Gower E, et al. Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis. Lancet Infect Dis. 2016;16:797–808.CrossRefGoogle Scholar
  2. 2.
    Sulkowski MS. Viral hepatitis and HIV coinfection. J Hepatol. 2008;48:353–367.CrossRefGoogle Scholar
  3. 3.
    Sulkowski MS, Mehta SH, Torbenson MS, et al. Rapid fibrosis progression among HIV/hepatitis C virus-co-infected adults. AIDS. 2007;21:2209–2216.CrossRefGoogle Scholar
  4. 4.
    Pineda JA, Romero-Gómez M, Díaz-García F, et al. HIV coinfection shortens the survival of patients with hepatitis C virus-related decompensated cirrhosis. Hepatology. 2005;41:779–789.CrossRefGoogle Scholar
  5. 5.
    Smith CJ, Ryom L, Weber R, et al. Trends in under lying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet. 2014;384:241–248.CrossRefGoogle Scholar
  6. 6.
    Torriani FJ, Rodriguez-Torres M, Rockstroh JK, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med. 2004;351:438–450.CrossRefGoogle Scholar
  7. 7.
    Chung RT, Andersen J, Volberding P, 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;351:451–459.CrossRefGoogle Scholar
  8. 8.
    Neukam K, Morano-Amado LE, Rivero-Juárez A, et al. HIV-coinfected patients respond worse to direct-acting antiviral-based therapy against chronic hepatitis C in real life than HCV-monoinfected individuals: a prospective cohort study. HIV Clin Trials. 2017;18:126–134.CrossRefGoogle Scholar
  9. 9.
    Simmons B, Saleem J, Heath K, Cooke GS, Hill A. Long-term treatment outcomes of patients infected with hepatitis C virus: a systematic review and meta-analysis of the survival benefit of achieving a sustained virological response. Clin Infect Dis. 2015;61:730–740.CrossRefGoogle Scholar
  10. 10.
    Rockstroh JK, Chung RT, Davis GL, et al. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;62:932–954.CrossRefGoogle Scholar
  11. 11.
    Saeed S, Strumpf EC, Walmsley SL, et al. How generalizable are the results from trials of direct antiviral agents to people coinfected with HIV/HCV in the real world? Clin Infect Dis. 2016;62:919–926.CrossRefGoogle Scholar
  12. 12.
    Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0. London The Cochrane Collaboration 2011.Google Scholar
  13. 13.
    Sterne J, Higgins JPT, Reeves B. Development Group for ROBINS-I. A tool for assessing Risk of Bias in Non-randomized Studies of Interventions. Version 5. 2016. www.riskofbias.info. Accessed August 3, 2016.
  14. 14.
    Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373:714–725.CrossRefGoogle Scholar
  15. 15.
    Wyles DL, Brau N, Kottilil S, et al. Sofosbuvir and velpatasvir for the treatment of HCV in patients infected with HIV-1: an open-label, phase 3 study. Clin Infect Dis. 2017;65:6–12.CrossRefGoogle Scholar
  16. 16.
    Rockstroh JK, Nelson M, Katlama C, 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:e319–e327.CrossRefGoogle Scholar
  17. 17.
    Sulkowski M, Hezode C, Gerstoft J, 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 randomized, open label phase 2 trial. Lancet. 2015;385:1087–1097.CrossRefGoogle Scholar
  18. 18.
    Naggie S, Cooper C, Saag M, et al. Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med. 2015;373:705–713.CrossRefGoogle Scholar
  19. 19.
    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;313:1232–1239.CrossRefGoogle Scholar
  20. 20.
    Molina JM, Orkin C, Iser DM, et al. “Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV(PHOTON-2): a multicenter, open-label, non-randomised, phase 3 study. The Lancet. 2015;385:1098–1106.CrossRefGoogle Scholar
  21. 21.
    Sulkowski MS, Eron JJ, Wyles D, 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;313:1223–1231.CrossRefGoogle Scholar
  22. 22.
    Patel M, Rab S, Kalapila AG, Kyle A, Okosun IS, Miller L. Highly successful hepatitis C virus (HCV) treatment outcomes in human immunodeficiency virus/HCV-coinfected patients at a large, urban, Ryan white clinic. Open Forum Infect Dis. 2017;4(2):ofx062.CrossRefGoogle Scholar
  23. 23.
    Bruno G, Saracino A, Luigia S, et al. HCV mono-infected and HIV/HCV co-infected individuals treated with direct-acting antivirals: to what extent do they differ? Int J Infect Dis. 2017;62:64–71.CrossRefGoogle Scholar
  24. 24.
    Falade-Nwulia O, Sutcliffe C, Moon J, Chander G, Wansom T, Keruly J, et al. High hepatitis C cure rates among black and nonblack human immunodeficiency virus-infected adults in an urban center. High hepatitis C cure rates among black and nonblack human immunodeficiency virus-infected adults in an urban center. Hepatology. 2017 Jun 13.  https://doi.org/10.1002/hep.29308. (Epub ahead of print).CrossRefGoogle Scholar
  25. 25.
    Hawkins C, Grant J, Ammerman LR, Palella F, Mclaughlin M, Green R. High rates of hepatitis C virus (HCV) cure using direct-acting antivirals in HIV/HCV-coinfected patients: a real-world perspective. J Antimicrob Chemother. 2016;71:2642–2645.CrossRefGoogle Scholar
  26. 26.
    Del Bello D, Cha A, Sorbera M, et al. Real-world sustained virologic response rates of sofosbuvir-containing regimens in patients coinfected with hepatitis C and HIV. Clin Infect Dis. 2016;62:1497–1504.CrossRefGoogle Scholar
  27. 27.
    Lacombe K, Fontaine H, Dhiver C, et al. Real-world efficacy of daclatasvir and sofosbuvir, with and without ribavirin, in HIV/HCV coinfected patients with advanced liver disease in a French early access cohort. J Acquir Immune Defic Syndr. 2017;75:97–107.CrossRefGoogle Scholar
  28. 28.
    Rockstroh JK, Ingiliz P, Petersen J, Peck-Radosavlievic Welzel TM, Van der Valk M, et al. Daclatasvir plus sofosbuvir, with or without ribavirin, in real-world patients with HIV-HCV coinfection and advanced liver disease. Antivir Ther. 2017;22:225–236.CrossRefGoogle Scholar
  29. 29.
    Milazzo L, Lai A, Calvi E, et al. Direct-acting antivirals in hepatitis C virus (HCV)-infected and HCV/HIV-coinfected patients: real-life safety and efficacy. HIV Med. 2017;18:284–291.CrossRefGoogle Scholar
  30. 30.
    Sogni P, Gilbert C, Lacombe K, et al. All-oral direct-acting antiviral regimens in HIV/hepatitis C virus-coinfected patients with cirrhosis are efficient and safe: real-life results from the prospective ANRS CO13-HEPAVIH cohort. Clin Infect Dis. 2016;63:763–770.CrossRefGoogle Scholar
  31. 31.
    Bhattacharya D, Belperio PS, Shahoumian TA, et al. Effectiveness of all-oral antiviral regimens in 996 human immunodeficiency virus/hepatitis C virus genotype 1-coinfected patients treated in routine practice. Clin Infect Dis. 2017;64:1711–1720.CrossRefGoogle Scholar
  32. 32.
    Iannou GN, Scott JD, Yang Y, Green PK, Beste LA. Rates and predictors of response to antiviral treatment for hepatitis C virus in HIV/HCV co-infection in a nationwide study of 619 patients. Aliment Pharmacol Ther. 2013;38:1373–1384.CrossRefGoogle Scholar
  33. 33.
    Cachay E, Hill L, Wyles D, et al. The hepatitis C cascade of care among HIV infected patients: a call to address ongoing barriers to care. PLoS ONE. 2014;9:e102883.CrossRefGoogle Scholar
  34. 34.
    Cachay E, Wyles D, Hill L, et al. The impact of direct-acting antivirals in the hepatitis C-sustained viral response in human immunodeficiency virus-infected patients with ongoing barriers to care. Open Forum Infect Dis. 2015;2(4):ofv168.CrossRefGoogle Scholar
  35. 35.
    Hagan H, Jordan AE, Neurer J, Cleland CM. Incidence of sexually transmitted hepatitis C virus infection in HIV positive men who have sex with men: a systematic review and meta-analysis. AIDS. 2015;29:2335–2345.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Departments of Surgery and MedicineUniversity of California at Los AngelesLos AngelesUSA
  2. 2.Pfleger Liver InstituteUCLA Medical CenterLos AngelesUSA

Personalised recommendations