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HIV Clin Trials. 2016 Mar;17(2):63-71. doi: 10.1080/15284336.2015.1135553. Epub 2016 Feb 11.

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.

Author information

1
a Aix-Marseille University, AP-HM Sainte-Marguerite, Service d'Immuno-Hématologie Clinique , Marseille , France.
2
b INSERM, UMR 912 (SESSTIM) , Marseille , France.
3
c Rennes 1 University, Pontchaillou University Hospital, Service de Pharmacologie , Rennes , France.
4
d INSERM, CIC 1414 Clinical Investigation Centre , Rennes , France.
5
e Nice University, Pasteur University Hospital , Laboratoire de Pharmacologie et de Toxicologie Médicale , Nice , France.
6
f Aix-Marseille University, AP-HM Timone, Fédération de Microbiologie Hospitalière , Marseille , France.
7
g URMITE , UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille , France.
8
h Bourgogne University, Bocage University Hospital , Département d'Infectiologie , UMR 1347, Dijon , France.
9
i Aix-Marseille University, AP-HM Timone, Service de Pharmacocinétique et Toxicologie , Marseille , France.
10
j INSERM , UMR 911 (CRO2), Marseille , France.
11
k AP-HM Saint-Joseph, Service d'Hépato-Gastro-Entérologie , Marseille , France.
12
l European Hospital , Marseille , France.
13
m Paris Descartes University , PRES Sorbonne Paris-Cité, EA 7327, Paris , France.
14
n Paris-Sud University, AP-HP Bicêtre Hospital, Service de Médecine Interne , Le Kremlin-Bicêtre, France.
15
o Toulouse 3 University, Purpan University Hospital, Service de Médecine Interne , Toulouse , France.
16
p Nice University, Archet University Hospital, Service d'Infectiologie , Nice , France.
17
q ORS PACA, Observatoire Régional de la Santé Provence-Alpes-Côte d'Azur , Marseille , France.
18
r Paris 7 - Denis Diderot University, AP-HP Saint-Louis Hospital, Service des Maladies Infectieuses et Tropicales , Paris , France.

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<0.01) and a 57% increase in RAL-AUC0-8 h (p<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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01335529.

KEYWORDS:

Boceprevir; Direct-acting antiviral drug; HCV retreatment; HIV/HCV coinfection

PMID:
27077673
DOI:
10.1080/15284336.2015.1135553
[Indexed for MEDLINE]
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