High Cure Rates With Grazoprevir-Elbasvir With or Without Ribavirin Guided by Genotypic Resistance Testing Among Human Immunodeficiency Virus/Hepatitis C Virus-coinfected Men Who Have Sex With Men.


Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213

Informations de publication

Date de publication:
01 02 2019
Historique:
received: 19 03 2018
accepted: 29 06 2018
pubmed: 15 8 2018
medline: 18 3 2020
entrez: 15 8 2018
Statut: ppublish

Résumé

This study was performed to investigate the efficacy and safety of grazoprevir-elbasvir guided by baseline resistance-associated substitutions (RASs) in the Swiss HCVree Trial. We performed hepatitis C virus (HCV) RNA screening among all men who have sex with men (MSM) enrolled in the Swiss HIV Cohort Study. Individuals with replicating HCV genotype 1 or 4 infection were eligible for grazoprevir-elbasvir treatment. Genotype 1a-infected individuals with baseline RASs and genotype 4-infected individuals with prior failure of HCV treatment received 16 weeks of grazoprevir-elbasvir combined with ribavirin. All other individuals received 12 weeks of grazoprevir-elbasvir alone. Patients reporting unprotected sex with occasional partners were offered a HCV risk reduction-oriented behavioral intervention. We screened 3722 MSM and identified 177 (4.8%) with replicating infection. A total of 122 individuals (3.3%) were eligible for study treatment. Six of 76 patients infected with genotype 1a (7.3%) harbored baseline RASs. Sustained virological response after 12 weeks of follow-up was achieved in 121 patients (99%), including all with genotype 1a infection. Overall, 8 serious adverse events occurred, none of which was related to the study drug. Seventy-five percent of eligible MSM participated in the risk counseling program. Grazoprevir-elbasvir for 12 or 16 weeks, with or without ribavirin, achieved high cure rates and had an excellent safety profile. Unique to other studies, the treatment duration was guided by the presence of baseline RASs among genotype 1a-infected individuals, and the treatment phase was accompanied by an HCV risk reduction-oriented behavioral intervention. This successful population-wide treatment approach lays the groundwork to achieve HCV elimination in coinfected MSM. NCT02785666.

Sections du résumé

Background
This study was performed to investigate the efficacy and safety of grazoprevir-elbasvir guided by baseline resistance-associated substitutions (RASs) in the Swiss HCVree Trial.
Methods
We performed hepatitis C virus (HCV) RNA screening among all men who have sex with men (MSM) enrolled in the Swiss HIV Cohort Study. Individuals with replicating HCV genotype 1 or 4 infection were eligible for grazoprevir-elbasvir treatment. Genotype 1a-infected individuals with baseline RASs and genotype 4-infected individuals with prior failure of HCV treatment received 16 weeks of grazoprevir-elbasvir combined with ribavirin. All other individuals received 12 weeks of grazoprevir-elbasvir alone. Patients reporting unprotected sex with occasional partners were offered a HCV risk reduction-oriented behavioral intervention.
Results
We screened 3722 MSM and identified 177 (4.8%) with replicating infection. A total of 122 individuals (3.3%) were eligible for study treatment. Six of 76 patients infected with genotype 1a (7.3%) harbored baseline RASs. Sustained virological response after 12 weeks of follow-up was achieved in 121 patients (99%), including all with genotype 1a infection. Overall, 8 serious adverse events occurred, none of which was related to the study drug. Seventy-five percent of eligible MSM participated in the risk counseling program.
Conclusions
Grazoprevir-elbasvir for 12 or 16 weeks, with or without ribavirin, achieved high cure rates and had an excellent safety profile. Unique to other studies, the treatment duration was guided by the presence of baseline RASs among genotype 1a-infected individuals, and the treatment phase was accompanied by an HCV risk reduction-oriented behavioral intervention. This successful population-wide treatment approach lays the groundwork to achieve HCV elimination in coinfected MSM.
Clinical Trials Registration
NCT02785666.

Identifiants

pubmed: 30107485
pii: 5071945
doi: 10.1093/cid/ciy547
doi:

Substances chimiques

Amides 0
Antiviral Agents 0
Benzofurans 0
Carbamates 0
Cyclopropanes 0
Imidazoles 0
Quinoxalines 0
Sulfonamides 0
Ribavirin 49717AWG6K
grazoprevir 4O2AB118LA
elbasvir 632L571YDK

Banques de données

ClinicalTrials.gov
['NCT02785666']

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

569-576

Investigateurs

A Anagnostopoulos (A)
M Battegay (M)
E B (E)
J B (J)
D L B (DL)
H C Bucher (HC)
A Calmy (A)
M Cavassini (M)
A Ciuffi (A)
G Dollenmaier (G)
M Egger (M)
L Elzi (L)
J S F (JS)
J Fellay (J)
H Furrer (H)
C A Fux (CA)
H F G (HF)
D Haerry (D)
B Hasse (B)
H H Hirsch (HH)
M Hoffmann (M)
I Hösli (I)
M Huber (M)
C Kahlert (C)
L Kaiser (L)
O Keiser (O)
T Klimkait (T)
R K (R)
H Kovari (H)
B Ledergerber (B)
G Martinetti (G)
B Martinez de Tejada (B)
C Marzolini (C)
K J Metzner (KJ)
N Müller (N)
D N (D)
P Paioni (P)
G Pantaleo (G)
M Perreau (M)
A R (A)
C Rudin (C)
A U Scherrer (AU)
P S (P)
R Speck (R)
M S (M)
P Tarr (P)
A Trkola (A)
P Vernazza (P)
G Wandeler (G)
R Weber (R)
S Yerly (S)

Commentaires et corrections

Type : CommentIn

Auteurs

Dominique L Braun (DL)

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland.
Institute of Medical Virology, University of Zurich.

Benjamin Hampel (B)

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland.
Institute of Medical Virology, University of Zurich.

Roger Kouyos (R)

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland.
Institute of Medical Virology, University of Zurich.

Huyen Nguyen (H)

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland.

Cyril Shah (C)

Institute of Medical Virology, University of Zurich.

Markus Flepp (M)

Center of Infectious Diseases Zurich.

Marcel Stöckle (M)

Division of Infectious Diseases & Hospital Epidemiology, University Hospital Basel, University of Basel.

Anna Conen (A)

Division of Infectious Diseases and Hospital Hygiene, Cantonal Hospital Aarau.

Charles Béguelin (C)

Department of Infectious Diseases, Bern University Hospital, University of Bern.

Patrizia Künzler-Heule (P)

Institute of Nursing Science, University Hospital Basel, University of Basel.

Dunja Nicca (D)

Institute of Nursing Science, University Hospital Basel, University of Basel.

Patrick Schmid (P)

Division of Infectious Diseases, Cantonal Hospital St Gallen.

Julie Delaloye (J)

Intensive Care Unit, Department of Intensive Care Medicine, University of Lausanne and University Hospital Center.

Mathieu Rougemont (M)

Division of Infectious Diseases, University Hospital Geneva.

Enos Bernasconi (E)

Division of Infectious Diseases, Regional Hospital Lugano.

Andri Rauch (A)

Department of Infectious Diseases, Bern University Hospital, University of Bern.

Huldrych F Günthard (HF)

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland.
Institute of Medical Virology, University of Zurich.

Jürg Böni (J)

Institute of Medical Virology, University of Zurich.

Jan S Fehr (JS)

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland.
Department Public Health, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Switzerland.

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