Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Jul 28;10(7):e0133879.
doi: 10.1371/journal.pone.0133879. eCollection 2015.

Ribavirin Concentrations Do Not Predict Sustained Virological Response in HIV/HCV-Coinfected Patients Treated with Ribavirin and Pegylated Interferon in the Swiss HIV Cohort Study

Helen Kovari  1 , Stefan Russmann  2 , Bruno Ledergerber  1 , Daniel Müller  3 , Margalida Rotger  4 , Pablo Velli  4 , Matthias Cavassini  5 , Juan Ambrosioni  6 , Andrea Bregenzer  7 , Marcel Stöckle  8 , Enos Bernasconi  9 , Andri Rauch  10 , Roberto F Speck  1 ; Swiss HIV Cohort Study
Affiliations

Ribavirin Concentrations Do Not Predict Sustained Virological Response in HIV/HCV-Coinfected Patients Treated with Ribavirin and Pegylated Interferon in the Swiss HIV Cohort Study

Helen Kovari et al. PLoS One. .

Abstract

Background: Ribavirin (RBV) is an essential component of most current hepatitis C (HCV) treatment regimens and still standard of care in the combination with pegylated interferon (pegIFN) to treat chronic HCV in resource limited settings. Study results in HIV/HCV-coinfected patients are contradicting as to whether RBV concentration correlates with sustained virological response (SVR).

Methods: We included 262 HCV treatment naïve HIV/HCV-coinfected Swiss HIV Cohort Study (SHCS) participants treated with RBV and pegIFN between 01.01.2001-01.01.2010, 134 with HCV genotype (GT) 1/4, and 128 with GT 2/3 infections. RBV levels were measured retrospectively in stored plasma samples obtained between HCV treatment week 4 and end of therapy. Uni- and multivariable logistic regression analyses were used to evaluate the association between RBV concentration and SVR in GT 1/4 and GT 2/3 infections. The analyses were repeated stratified by treatment phase (week 4-12, 13-24, >24) and IL28B genotype (CC versus CT/TT).

Results: SVR rates were 35.1% in GT 1/4 and 70.3% in GT 2/3 infections. Overall, median RBV concentration was 2.0 mg/L in GT 1/4, and 1.9 mg/L in GT 2/3, and did not change significantly across treatment phases. Patients with SVR had similar RBV concentrations compared to patients without SVR in both HCV genotype groups. SVR was not associated with RBV levels ≥2.0 mg/L (GT 1/4, OR 1.19 [0.5-2.86]; GT 2/3, 1.94 [0.78-4.80]) and ≥2.5 mg/L (GT 1/4, 1.56 [0.64-3.84]; GT 2/3 2.72 [0.85-8.73]), regardless of treatment phase, and IL28B genotype.

Conclusion: In HIV/HCV-coinfected patients treated with pegIFN/RBV, therapeutic drug monitoring of RBV concentrations does not enhance the chance of HCV cure, regardless of HCV genotype, treatment phase and IL28B genotype.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The study was funded within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant # 148522), by SHCS project #650, and by an unrestricted grant from Roche Pharma AG. Roche Pharma AG had no influence on the study design, or the collection, analysis, and interpretation of the data. They were not involved in writing the manuscript or in the submission process. Roche Pharma AG has not seen the manuscript yet. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Patient flowchart.
Fig 2
Fig 2. Comparison of ribavirin concentrations between HIV/HCV-coinfected patients with and without sustained virological response (SVR), stratified by HCV genotype and treatment phase.
Abbreviations: SVR, sustained virological response; 0, no SVR; 1, SVR.
Fig 3
Fig 3. Impact of ribavirin level ≥2.0 mg/L and ≥2.5 mg/L on sustained virological response (SVR), stratified by HCV genotype group, treatment phase and IL28B genotype.
Multivariable logistic regression analysis, adjusted for age, sex, HIV transmission group and HCV RNA level. Abbreviations: CI, confidence interval; HCV, hepatitis C virus; OR, odds ratio; RBV, ribavirin.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Guidelines for the Screening, Care and Treatment of Persons with Hepatitis C Infection WHO Guidelines Approved by the Guidelines Review Committee. Geneva: 2014. - PubMed
    1. European Association for Study of L. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. Journal of hepatology. 2014;60(2):392–420. 10.1016/j.jhep.2013.11.003 - DOI - PubMed
    1. Russmann S, Grattagliano I, Portincasa P, Palmieri VO, Palasciano G. Ribavirin-induced anemia: mechanisms, risk factors and related targets for future research. Current medicinal chemistry. 2006;13(27):3351–7. - PubMed
    1. Jen JF, Glue P, Gupta S, Zambas D, Hajian G. Population pharmacokinetic and pharmacodynamic analysis of ribavirin in patients with chronic hepatitis C. Therapeutic drug monitoring. 2000;22(5):555–65. - PubMed
    1. Slavenburg S, Huntjens-Fleuren HW, Dofferhoff TS, Richter C, Koopmans PP, Verwey-Van Wissen CP, et al. Ribavirin plasma concentration measurements in patients with hepatitis C: early ribavirin concentrations predict steady-state concentrations. Therapeutic drug monitoring. 2011;33(1):40–4. 10.1097/FTD.0b013e318205f892 - DOI - PubMed

Publication types

MeSH terms