International Journal of Clinical Pharmacy

, Volume 41, Issue 6, pp 1545–1554 | Cite as

Measure of adherence to direct-acting antivirals as a predictor of the effectiveness of hepatitis C treatment

  • María Ángeles Campos Fernández de SevillaEmail author
  • Marta Gallego Úbeda
  • Maria Tovar Pozo
  • Emilio García-Cabrera
  • Beatriz Monje García
  • Federico Tutau Gómez
  • Laura Delgado Téllez de Cepeda
  • Irene Iglesias-Peinado
Research Article


Background Adherence to direct-acting antivirals could be a predictor response to these treatments in hepatitis C. Objective To assess the ability of three methods of measuring adherence to direct-acting antivirals [pill counts, pharmacy dispensing record and Simplified Medication Adherence Questionnaire (SMAQ)] as predictors of their effectiveness. Setting Study conducted by the pharmacy department of the hospital. Methods: A retrospective study was performed. Patients ≥ 18 years with hepatitis C that started and completed treatment with direct-acting antivirals between the 1st-April-2015 and 28st-February-2016 were enrolled. To evaluate the predictive ability to obtain a response to treatment, Chi squared test, Mann–Whitney-U test and ROC-curves were used. Main outcome measure Adherence to antivirals was assessed by three methods and response to treatment, which was defined as obtaining a viral load of hepatitis C virus ≤ 15UI/ml at week 12 after the end of treatment. Results 128 patients were enrolled. The overall average adherence obtained with SMAQ (99.09%) was similar to the pill counts (96.40%, p = 0.043) and pharmacy dispensing record (91.10%, p = 0.02). There was no correlation between the percentage of patients considered as adherent by SMAQ (99.09%) and the achievement of response to treatment (96.40%, p = 0.999). The ROC-curve obtained for the pill count method shows a global area under the curve of 0.53. For pharmacy dispensing record method, patients with an adherence ≤ 66.66% have a high probability of not achieving response (sensitivity and specificity of 79.00% and 100.00%, respectively). Conclusions Pharmacy dispensing record is shown as the best indicator of adherence to predict therapeutic failure in our study.


Adherence Antivirals Chronic hepatitis C Infectious diseases Spain 



The authors thank Javier Fernández de Sevilla for help with English language.


The authors declare that they have not received any type of financing for the realization of this study.

Conflicts of interest

All authors confirm that there are no known conflicts of interest associated with this publication.


  1. 1.
    Terrault N, Monto A, Stinchon MR, Rusie E, Moreo K. New therapies, evidence, and guidance in hepatitis C management: expert practices and insights from an educational symposium at the AMCP 27th annual meeting expo. J Manag Care Spec Pharm. 2015;21(9):S1–14.PubMedGoogle Scholar
  2. 2.
    Yang HJ, Ryoo JY, Yoo BK. Meta-analysis of the efficacy and safety of sofosbuvir for the treatment of hepatitis C virus infection. Int J Clin Pharm. 2015;37(5):698–708.CrossRefGoogle Scholar
  3. 3.
    Puenpatom A, Hull M, McPheeters J, Schwebke K. Treatment discontinuation, adherence, and real-world effectiveness among patients treated with ledipasvir/sofosbuvir in the United States. Infect Dis Ther. 2017;6(3):423–33.CrossRefGoogle Scholar
  4. 4.
    Benítez García B, González del Valle L, Capilla Santamaría E, Perez Robles T, Herrero Ambrosio A. CPC-062 hepatitis C and adherence. Eur J Hosp Pharm. 2013;20((Suppl 1)):A187–8.Google Scholar
  5. 5.
    The American Association for the Study of Liver Diseases and the Infectious Disease Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Introduction. From Sept. 2017; vol. 21.
  6. 6.
    Petersen T, Townsend K, Gordon LA, Sidharthan S, Silk R, Nelson A, et al. High adherence to all-oral directly acting antiviral HCV therapy among an inner-city patient population in a phase 2a study. Hepatol Int. 2016;10(2):310–9.CrossRefGoogle Scholar
  7. 7.
    Walker DR, Juday TR, Manthena SR, Jing Y, Sood V. The impact of ribavirin on real-world adherence rates in hepatitis C patients treated with sofosbuvir plus simeprevir. Clin Outcomes Res. 2015;7:637–42.Google Scholar
  8. 8.
    Burton MJ, Voluse AC, Patel AB, Konkle-Parker D. Measuring adherence to hepatitis C direct-acting antiviral medications: using the VAS in an HCV treatment clinic. South Med J. 2018;111(1):45–50.CrossRefGoogle Scholar
  9. 9.
    Knobel H, Alonso J, Casado JL, Collazos J, González J, Ruiz I, et al. Validation of a simplied medication adherence questionnaire in a large cohort of HIV-infected patients: the GEEMA study. Aids. 2002;16(4):605–13.CrossRefGoogle Scholar
  10. 10.
    Morisky DE, Green LW, Levine DM. Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care. 1986;24(1):67–74.CrossRefGoogle Scholar
  11. 11.
    European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2014. J Hepatol. 2014;61(2):373–95.CrossRefGoogle Scholar
  12. 12.
    De Geest S, Zullig LL, Dunbar-Jacob J, Helmy R, Hughes DA, Wilson IB, et al. ESPACOMP Medication Adherence Reporting Guideline (EMERGE). Ann Intern Med. 2018;169(1):30–5.CrossRefGoogle Scholar
  13. 13.
    Steiner JF, Prochazka AV. The assessment of refill compliance using pharmacy records: methods, validity, and applications. J Clin Epidemiol. 1997;50(1):105–16.CrossRefGoogle Scholar
  14. 14.
    Vo KP, Vutien P, Akiyama MJ, Vu VD, Ha NB, Piotrowski JI, et al. Poor sustained virological response in a multicenter real-life cohort of chronic hepatitis C patients treated with pegylated interferon and ribavirin plus telaprevir or boceprevir. Dig Dis Sci. 2015;60(4):1045–51.CrossRefGoogle Scholar
  15. 15.
    Younossi ZM, Stepanova M, Henry L, Nader F, Younossi Y, Hunt S. Adherence to treatment of chronic hepatitis C: from interferon containing regimens to interferon and ribavirin free regimens. Medicine. 2016;95(28):e4151.CrossRefGoogle Scholar
  16. 16.
    Viciana P, Rubio R, Ribera E, Knobel H, Iribarren JA, Arribas JR, et al. Longitudinal study on adherence, treatment satisfaction, and effectiveness of once-daily versus twice-daily antiretroviral therapy in a Spanish cohort of HIV-infected patients (CUVA study). Enferm Infecc Microbiol Clin. 2008;26(3):127–34.CrossRefGoogle Scholar
  17. 17.
    Chamorro-de-Vega E, Gimenez-Manzorro A, Rodriguez-Gonzalez C-G, Escudero-Vilaplana V, De Lorenzo-Pinto A, Iglesias-Peinado I, et al. Twelve weeks of ombitasvir/paritaprevir/r and dasabuvir without ribavirin is effective and safe in the treatment of patients with HCV genotype 1b infection and compensated cirrhosis: results from a real-world cohort study. Expert Opin Drug Saf. 2018;11:1–7.Google Scholar
  18. 18.
    Ji F, Wei B, Yeo YH, Ogawa E, Zou B, Stave CD, et al. Systematic review with meta-analysis: effectiveness and tolerability of interferon-free direct-acting antiviral regimens for chronic hepatitis C genotype 1 in routine clinical practice in Asia. Aliment Pharmacol Ther. 2018;47(5):550–62.CrossRefGoogle Scholar
  19. 19.
    Nogués Solán X, Sorli Redó ML, Villar García J. Tools to measure treatment adherence. Ann Med Int. 2007;24(3):138–41.Google Scholar
  20. 20.
    Mathes T, Antoine S-L, Pieper D. Factors influencing adherence in hepatitis-C infected patients: a systematic review. BMC Infect Dis. 2014;14:203.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Clinical Pharmacy, Pharmacy DepartmentHospital Universitario del HenaresCoslada, MadridSpain
  2. 2.Delos ClinicalSevilleSpain
  3. 3.PharmD and Clinical Pharmacy, Pharmacy DepartmentHospital Universitario del HenaresCoslada, MadridSpain
  4. 4.PharmD, Faculty of PharmacyUniversidad Complutense de MadridMadridSpain

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