International Journal of Clinical Pharmacy

, Volume 40, Issue 3, pp 608–616 | Cite as

Effectiveness and security of chronic hepatitis C treatment in coinfected patients in real-world

  • Moisés Uriarte-PintoEmail author
  • Herminia Navarro-Aznarez
  • Natalia De La Llama-Celis
  • Piedad Arazo-Garcés
  • Ana María Martínez-Sapiña
  • María Reyes Abad-Sazatornil
Research Article


Background HIV–HCV coinfection produces high morbi-mortality. Direct-acting antivirals (DAAs) have shown high efficacy, although special attention should be paid to the risk of drug interactions. However, due to the lack of representativeness of coinfected patients in clinical trials, it is important to know real-world results. Objective To evaluate DAA treatment effectiveness in coinfected patients. We also analyse safety profile of DAA treatment and drug interactions between HCV and HIV therapy. Setting Descriptive study carried in a tertiary hospital of Spain Method HIV–HCV coinfected patients treated with DAAs between November 2014 and June 2016 were included. Main outcome measure Efficacy was measured in terms of sustained virologic response at week 12 after the end of therapy. Adverse events that led to treatment discontinuation were registered to evaluate the safety profile, and also drug interactions between DAAs and antiretroviral treatment were evaluated. Results Main HCV genotypes were 1a (34.9%) and 4 (24.5%). 51.9% were HCV previously treated, 54.7% had grade 4 liver fibrosis. SVR12 was reported in 90.6%. HCV treatment was well tolerated and there were no discontinuations because of adverse events. 30.2% of HIV treatments had to be modified before DAA treatment was started due to interactions, HIV suppression was not compromised. Conclusion DAA treatment in coinfected patients seems to be highly effective and secure. Evaluation of drug interactions must be a priority in order to maximize effectiveness and avoid toxicity.


Antiretroviral therapy Direct-acting antivirals Drug-drug interactions HIV-HCV Coinfection Sustained virologic response 



This study did not receive special funding.

Conflicts of interest

All the authors declare that they have no conflict of interest.


  1. 1.
    Mandorfer M, Schwabl P, Steiner S, Reiberger T, Peck-Radosavljevic M. Advances in the management of HIV/HCV coinfection. Hepatol Int. 2016;10:424–35.CrossRefPubMedGoogle Scholar
  2. 2.
    WHO. Fact sheet hepatitis C 2015. World Health Organization. Accessed 9 Feb 2017.
  3. 3.
    Yaphe S, Bozinoff N, Kyle R, Shivkumar S, Pai NP, Klein M. Incidence of acute hepatitis C virus infection among men who have sex with men with and without HIV infection: a systematic review. Sex Transm Infect. 2012;88:558–64.CrossRefPubMedGoogle Scholar
  4. 4.
    Crespo M, Von Wichmann MA. Manejo de las hepatitis virales en pacientes infectados por el VIH. Guía de Práctica Clínica de GeSIDA. Accessed 9 Feb 2017.
  5. 5.
    Hull M, Klein M, Shafran S, Tseng A, Giguère P, Côté P, et al. CIHR Canadian HIV trials network coinfection and concurrent diseases core: Canadian guidelines for management and treatment of HIV/hepatitis C coinfection in adults. Can J Infect Dis Med Microbiol. 2013;24:217–38.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    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;33:562–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Poveda E, Wyles D, Morano L, Pineda JA, García F. News on HIV–HCV Coinfection: update from the 2015 GEHEP conference. AIDS Rev. 2015;17:231–7.PubMedGoogle Scholar
  8. 8.
    Operskalski EA, Kovacs A. HIV/HCV co-infection: pathogenesis, clinical complications, treatment, and new therapeutic technologies. Curr HIV/AIDS Rep. 2011;8:12–22.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Berenguer J, Álvarez-Pellicer J, Martín PM, López-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;50:407–13.CrossRefPubMedGoogle Scholar
  10. 10.
    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;61:730–40.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Berenguer J, Rodríguez E, Miralles P, Von Wichmann MA, López-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;55:728–36.CrossRefPubMedGoogle Scholar
  12. 12.
    Mariño Z, Lens S, Gambato M, Forns X. Advances in hepatitis C therapies. Expert Opin Pharmacother. 2015;16:1929–43.CrossRefPubMedGoogle Scholar
  13. 13.
    EASL Clinical Practice Guidelines. Management of hepatitis C virus infection. J Hepatol. 2014;60:392–420.CrossRefGoogle Scholar
  14. 14.
    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;312:353–61.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    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;373:705–13.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    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;373:714–25.CrossRefPubMedGoogle Scholar
  17. 17.
    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;313:1223–31.CrossRefPubMedGoogle Scholar
  18. 18.
    Soriano V, Labarga P, Barreiro P, Fernandez-Montero JV, de Mendoza C, Esposito I, et al. Drug interactions with new hepatitis C oral drugs. Expert Opin Drug Metab Toxicol. 2015;11:333–41.CrossRefPubMedGoogle Scholar
  19. 19.
    Kiser JJ, Burton JR, Everson GT. Drug–drug interactions during antiviral therapy for chronic hepatitis C. Nat Rev Gastroenterol Hepatol. 2013;10:596–606.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Soriano V, Labarga P, de Mendoza C, Fernández-Montero JV, Esposito I, Benítez-Gutiérrez L, et al. New hepatitis C therapies for special patient populations. Exp Opin Pharmacother. 2016;17(2):217–29.CrossRefGoogle Scholar
  21. 21.
    Shafran SD. HIV coinfected have similar SVR rates as HCV monoinfected with DAAs: it’s time to end segregation and integrate HIV patients into HCV trials. Clin Infect Dis. 2015;61:1127–34.CrossRefPubMedGoogle Scholar
  22. 22.
    Saeed S, Strumpf EC, Walmsley SL, Rollet-Kurhajec K, Pick N, Martel-Laferrière V, 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;62:919–26.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Menard A, Colson P, Catherine D, Isabelle R, Christelle T, Meddeb L, et al. First real life evidence of new direct-acting antivirals (DAA) in co-infected HIV HCV patients: better than ever. Clin Infect Dis. 2016;62:947–9.CrossRefPubMedGoogle Scholar
  24. 24.
    University of Liverpool. HEP drug interactions. Accessed 10 Feb 2017.
  25. 25.
    Lexicomp. Accessed 10 Feb 2017.
  26. 26.
    Agencia Española de Medicamentos y Productos Sanitarios—Ministerio de Sanidad Servicios Sociales e Igualdad. Accessed 10 Feb 2017.
  27. 27.
    Greub G, Ledergerber B, Battegay M, Grob P, Perrin L, Furrer H, et al. Clinical progression, survival, and immune recovery during antiretroviral therapy in patients with HIV-1 and hepatitis C virus coinfection: the Swiss HIV Cohort Study. Lancet. 2000;356:1800–5.CrossRefPubMedGoogle Scholar
  28. 28.
    Kohli A, Shaffer A, Sherman A, Kottilil S. Treatment of hepatitis C: a systematic review. JAMA. 2014;312:631–40.CrossRefPubMedGoogle Scholar
  29. 29.
    AEEH y SEIMC. Documento del III Consenso español sobre tratamiento de la hepatitis C. 2016. Accessed 10 Feb 2017.
  30. 30.
    Berenguer J, Rivero A, Jarrín I, Núñez MJ, Vivancos MJ, Crespo M, et al. Human immunodeficiency virus/hepatitis C virus coinfection in Spain: prevalence and patient characteristics. Open Forum Infect Dis. 2016;3(2):ofw059. Scholar
  31. 31.
    Cavalcante LN, Lyra AC. Predictive factors associated with hepatitis C antiviral therapy response. World J Hepatol. 2015;7:1617–31.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Zhang J, Nguyen D, Hu K-Q. Chronic hepatitis C virus infection: a review of current direct-acting antiviral treatment strategies. N Am J Med Sci. (Boston). 2016;9:47–54.Google Scholar
  33. 33.
    Nelson DR, Cooper JN, Lalezari JP, Lawitz E, Pockros PJ, Gitlin N, et al. All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study. Hepatology. 2015;61:1127–35.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Hézode 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;385:2502–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Chen T-Y, Jain MK. Treatment of hepatitis C in HIV-infected patients: moving towards an era of all oral regimens. AIDS Patient Care STDS. 2015;29:329–37.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Sulkowski MS, Vargas HE, Di Bisceglie AM, Kuo A, Reddy KR, Lim JK, et al. Effectiveness of Simeprevir plus Sofosbuvir, with or without ribavirin, in real-world patients with HCV genotype 1 infection. Gastroenterology. 2016;150:419–29.CrossRefPubMedGoogle Scholar
  37. 37.
    Lakshmi S, Alcaide M, Palacio AM, Shaikhomer M, Alexander AL, Gill-Wiehl G, et al. Improving HCV cure rates in HIV-coinfected patients—a real-world perspective. Am J Manag Care. 2016;22:SP198–204.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Pineda JA, Núñez-Torres R, Téllez F, Mancebo M, García F, Merchante N, et al. Hepatitis C virus reinfection after sustained virological response in HIV-infected patients with chronic hepatitis C. J Infect. 2015;71:571–7.CrossRefPubMedGoogle Scholar
  39. 39.
    Midgard H, Bjøro B, Mæland A, Konopski Z, Kileng H, Damås JK, et al. Hepatitis C reinfection after sustained virological response. J Hepatol. 2016;64:1020–6.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Moisés Uriarte-Pinto
    • 1
    Email author
  • Herminia Navarro-Aznarez
    • 1
  • Natalia De La Llama-Celis
    • 1
  • Piedad Arazo-Garcés
    • 2
  • Ana María Martínez-Sapiña
    • 3
  • María Reyes Abad-Sazatornil
    • 1
  1. 1.Pharmacy DepartmentMiguel Servet University HospitalSaragossaSpain
  2. 2.Unit of Infectious DiseasesMiguel Servet University HospitalSaragossaSpain
  3. 3.Microbiology DepartmentMiguel Servet University HospitalSaragossaSpain

Personalised recommendations