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Addition of boceprevir to PEG-interferon/ribavirin in HIV-HCV-Genotype-1-coinfected, treatment-experienced patients: efficacy, safety, and pharmacokinetics data from the ANRS HC27 study

Isabelle Poizot-Martin 1, 2, * Eric Bellissant 3, 4 Rodolphe Garraffo 5 Philippe Colson 6 Lionel Piroth 7, 8 Caroline Solas 9, 10 Alain Renault 4, 11 Marc Bourlière 12 Philippe Halfon 13 Jade Ghosn 14 Laurent Alric 15 Alissa Naqvi 16 Patrizia Carrieri 2, 17 Jean-Michel Molina 18, 19
* Corresponding author
1 Département de Recherche CLinique
2 SESSTIM - U912 INSERM - Aix Marseille Univ - IRD - Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale
3 Department of clinical and biological pharmacology and pharmacovigilance
4 CIC - Centre d'Investigation Clinique [Rennes]
5 Service de pharmacologie
6 URMITE - Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes
7 Département d'infectiologie (CHU de Dijon)
8 Agroécologie [Dijon]
9 Service de Pharmacocinétique et de Toxicologie
10 CRO2 - Centre de Recherches en Oncologie biologique et Oncopharmacologie
11 Service de Pharmacologie
12 Service d'hépato-gastro-entérologie
13 Internal Medicine and Infectious Diseases Department
14 EA 7327 - Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV)
15 PHARMA-DEV - Pharmacochimie et Biologie pour le Développement
16 Service de Maladies Infectieuses [Nice]
17 Observatoire Régional de la Santé Provence Alpes Côte d'Azur
18 Service des Maladies Infectieuses et Tropicales [CHU Saint Louis]
19 Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales
Abstract : Background: Scarce data exist on the efficacy and safety of the PEGylated-interferon/ribavirin/boceprevir regimen in HIV/HCV-coinfected patients who failed to respond to PEGylated-interferon/ribavirin treatment.Objectives: To evaluate the efficacy and safety of this drug regimen and the impact of the addition of boceprevir(BOC) on atazanavir (ATV) or raltegravir (RAL) pharmacokinetic parameters in a subgroup of patients.Methods: In this single-arm phase 2 trial, HIV-1/HCV-genotype-1-coinfected patients received PEGylated-interferonα2b (1.5 μg/kg/week)+ ribavirin (800–1400 mg/day) alone until W4 and with BOC(800 mgTID) until W48. Based on virologic response at W8, the three drugs were stopped or PEGylated-interferon/ribavirin was continued alone until W72. The primary endpoint was SVR at W24 off-therapy (SVR24). Results: 64 patients were included. SVR24 was achieved in 53% of patients (CI90%: 43–63%) and in 90% of previous relapsers. In univariate analysis, SVR24 was associated with response to previous HCV treatment, HCV-1b subtype, HCV-RNA decline, ribavirin-Ctrough at W4, and HCV-RNA at W8 but not to fibrosis score, IL28B genotype, or boceprevir-Ctrough at W8. In multivariate analysis, SVR24 remained associated with response to previous HCV treatment [non-responders versus null responders: OR = 5.0(1.3–20.0); relapsers vs. null responders: OR = 28.8(4.9–169.5)]. HCV treatment was discontinued for adverse events in 17% of patients. A 51% decrease in ATV/r-AUC0–8 h (p \textless 0.01) and a 57% increase in RAL-AUC0–8 h (p \textless 0.01) were observed, although atazanavir/r or raltegravir did not affect BOC-AUC0–8 h significantly. The ATV mean Cthrough fell from 763.8 ng/mL (CI 95%: 230.3–1297.3) without BOC to 507.7 ng/mL (CI 95%: 164–851.4) with BOC.Conclusions: Boceprevir-based regimen demonstrated a high SVR24 rate in treatment-experienced HIV-HCV genotype-1-coinfected relapsers.
Keywords : HIV/HCV coinfection HCV retreatment boceprevir direct acting antiviral drug
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-01299973
Contributor : Laurent Jonchère <>
Submitted on : Friday, June 3, 2016 - 4:04:43 PM
Last modification on : Wednesday, August 19, 2020 - 12:08:10 PM

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CNRS | UNIV-BOURGOGNE | INRA | UNIV-RENNES1 | UNIV-PARIS5 | IRD | CIC | CIC203 | BIOSIT | UNIV-AMU | UR1-UFR-SVE | USPC | AGROECOLOGIE | UNIV-COTEDAZUR | UNIV-RENNES | U1252 | UNIV-PARIS7 | UNIV-TLSE3 | INC-CNRS | INRAE | UNIV-PARIS

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Isabelle Poizot-Martin, Eric Bellissant, Rodolphe Garraffo, Philippe Colson, Lionel Piroth, et al.. Addition of boceprevir to PEG-interferon/ribavirin in HIV-HCV-Genotype-1-coinfected, treatment-experienced patients: efficacy, safety, and pharmacokinetics data from the ANRS HC27 study. HIV Clinical Trials, Thomas Land Publishers, 2016, 17 (2), pp.63-71. ⟨10.1080/15284336.2015.1135553⟩. ⟨hal-01299973⟩

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