A Lead-In with Silibinin Prior to Triple-Therapy Translates into Favorable Treatment Outcomes in Difficult-To-Treat HIV/Hepatitis C Coinfected Patients.

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Serval ID
serval:BIB_AE145D79EBD4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A Lead-In with Silibinin Prior to Triple-Therapy Translates into Favorable Treatment Outcomes in Difficult-To-Treat HIV/Hepatitis C Coinfected Patients.
Journal
Plos One
Author(s)
Braun D.L., Rauch A., Aouri M., Durisch N., Eberhard N., Anagnostopoulos A., Ledergerber B., Müllhaupt B., Metzner K.J., Decosterd L., Böni J., Weber R., Fehr J.
Working group(s)
Swiss HIV Cohort Study
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
10
Number
7
Pages
e0133028
Language
english
Notes
Publication types: Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't Publication Status: epublish
Abstract
BACKGROUND: The efficacy of first-generation protease inhibitor based triple-therapy against hepatitis C virus (HCV) infection is limited in HIV/HCV-coinfected patients with advanced liver fibrosis and non-response to previous peginterferon-ribavirin. These patients have a low chance of achieving a sustained virologic response (SVR) using first generation triple-therapy, with a success rate of only 20%. We investigated the efficacy and safety of lead-in therapy with intravenous silibinin followed by triple-therapy in this difficult-to-treat patient group.
METHODOLOGY: Inclusion criteria were HIV/HCV coinfection with advanced liver fibrosis and documented previous treatment failure on peginterferon-ribavirin. The intervention was a lead-in therapy with intravenous silibinin 20 mg/kg/day for 14 days, followed by triple-therapy (peginterferon-ribavirin and telaprevir) for 12 weeks, and peginterferon-ribavirin alone for 36 weeks. Outcome measurements were HCV-RNA after silibinin lead-in and during triple-therapy, SVR data at week 12, and safety and tolerability of silibinin.
RESULTS: We examined sixteen HIV/HCV-coinfected patients with previous peginterferon-ribavirin failure, of whom 14 had a fibrosis grade METAVIR ≥F3. All were on successful antiretroviral therapy. Median (IQR) HCV-RNA decline after silibinin therapy was 2.65 (2.1-2.8) log10 copies/mL. Fifteen of sixteen patients (94%) had undetectable HCV RNA at weeks 4 and 12, eleven patients (69%) showed end-of-treatment response (i.e., undetectable HCV-RNA at week 48), and ten patients (63%) reached SVR at week 12 (SVR 12). Six of the sixteen patients (37%) did not reach SVR 12: One patient had rapid virologic response (RVR) (i.e., undetectable HCV-RNA at week 4) but stopped treatment at week 8 due to major depression. Five patients had RVR, but experienced viral breakthroughs at week 21, 22, 25, or 32, or a relapse at week 52. The HIV RNA remained below the limit of detection in all patients during the complete treatment period. No serious adverse events and no significant drug-drug interactions were associated with silibinin.
CONCLUSION: A lead-in with silibinin before triple-therapy was safe and highly effective in difficult-to-treat HIV/HCV coinfected patients, with a pronounced HCV-RNA decline during the lead-in phase, which translates into 63% SVR. An add-on of intravenous silibinin to standard of care HCV treatment is worth further exploration in selected difficult-to-treat patients.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01816490.
Keywords
Adult, Antiretroviral Therapy, Highly Active, Antiviral Agents/therapeutic use, Coinfection, Drug Administration Schedule, Female, HIV/drug effects, HIV/growth & development, HIV Infections/blood, HIV Infections/drug therapy, Hepacivirus/drug effects, Hepacivirus/growth & development, Hepatitis C, Chronic/blood, Hepatitis C, Chronic/drug therapy, Humans, Injections, Intravenous, Interferon-alpha/therapeutic use, Liver Cirrhosis/blood, Liver Cirrhosis/drug therapy, Male, Middle Aged, Oligopeptides/therapeutic use, Patient Safety, Polyethylene Glycols/therapeutic use, Prospective Studies, Protease Inhibitors/therapeutic use, RNA, Viral/antagonists & inhibitors, RNA, Viral/blood, Recombinant Proteins/therapeutic use, Ribavirin/therapeutic use, Silymarin/therapeutic use, Treatment Outcome, Viral Load/drug effects
Pubmed
Web of science
Open Access
Yes
Create date
27/08/2015 9:47
Last modification date
20/08/2019 15:17
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