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Clin Infect Dis. 2015 Sep 1;61(5):817-25. doi: 10.1093/cid/civ381. Epub 2015 May 14.

High Cure Rate With 24 Weeks of Daclatasvir-Based Quadruple Therapy in Treatment-Experienced, Null-Responder Patients With HIV/Hepatitis C Virus Genotype 1/4 Coinfection: The ANRS HC30 QUADRIH Study.

Author information

1
Infectious Diseases Department, Centre Hospitalo-Universitaire, and Unité Mixte de Recherche (UMR)1347, Université de Bourgogne, Dijon.
2
Institut National de la Santé et de la Recherche Médicale (INSERM) SC10-US019, Villejuif.
3
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Bicêtre, Hôpitaux Universitaires Paris Sud, Clinical Pharmacy.
4
Service de Médecine Interne, Hôpital de l'Archet, and Université de Nice-Sophia Antipolis.
5
Sorbonne Universités, Université Pierre et Marie CURIE (UPMC) Paris 06, INSERM UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, and Service de maladies infectieuses, Hôpital Saint-Antoine, AP-HP.
6
Infectious Diseases Department, Centre Hospitalo-Universitaire, Nantes.
7
Le Trait d'Union, Hôpitaux Universitaires, Strasbourg.
8
Infectious Diseases Department, Hôpital Foch, Suresnes.
9
Department of Hepatology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon.
10
INSERM U954, Centre Hospitalier Universitaire de Nancy, Université de Lorraine, Vandoeuvre les Nancy.
11
Agence Nationale de Recherche sur le Sida et les Hépatites Virales, France REcherche Nord & sud Sida-hiv Hépatites, Paris.
12
Department of Virology, INSERM U1043 IFR-BMT, and Université Paul Sabatier, Toulouse.
13
Infectious Diseases Department, Hôpital Saint-Louis-AP-HP, and Université Paris Diderot, Sorbonne Paris Cité, France.

Abstract

BACKGROUND:

Few direct anti-hepatitis C virus (HCV) agents have been studied in difficult-to-treat null responder and cirrhotic human immunodeficiency virus (HIV)-coinfected patients. Daclatasvir and asunaprevir combined with pegylated interferon/ribavirin (peg-IFN/RBV) have shown promising results in HCV-monoinfected patients.

METHODS:

An open-label, single-arm, phase 2 study was conducted in HIV/HCV genotype 1/4-coinfected patients who were null responders to prior peg-IFN/RBV standard therapy and on a raltegravir-based regimen with HIV RNA <400 copies/mL. They received a 4-week lead-in phase with peg-IFN/RBV, followed by 24 weeks of asunaprevir (100 mg twice daily), daclatasvir (60 mg once daily), and peg-IFN/RBV. The primary endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12) using intent-to-treat analysis.

RESULTS:

Seventy-five patients were included, of whom 27 (36%) had cirrhosis. The median baseline CD4 count was 748 (interquartile range, 481-930) cells/µL. The global SVR12 rate was 96.0% (95% confidence interval [CI], 88.8%-99.2%; n = 72/75), 92.6% (95% CI, 75.7%-99.1%; n = 25/27) in cirrhotic patients, 94.6% (95% CI, 81.8%-99.3%; n = 35/37) in genotype 1 patients, and 97.4% (95% CI, 86.2%-99.9%; n = 37/38) in genotype 4 patients. Six patients (8%) stopped HCV therapy prematurely: 2 due to HCV breakthrough, 4 to adverse events (1 lung cancer, 3 infections). One patient with cirrhosis (with baseline platelet count <150 000 platelets/µL and albuminemia <35 g/L) died from multiorgan failure. Overall, 36 serious adverse events occurred in 21 (28%) patients. No HIV breakthrough was observed.

CONCLUSIONS:

In HIV/HCV genotype 1/4-coinfected null responders, a 24-week regimen combining daclatasvir, asunaprevir, and peg-IFN/RBV was associated with a very high cure rate. The safety profile was acceptable, even though cirrhotic patients with low albuminemia and platelets should be monitored closely. This combination is a new option in this difficult-to-treat population.

CLINICAL TRIALS REGISTRATION:

NCT01725542.

KEYWORDS:

HCV; HIV; asunaprevir; cirrhosis; daclatasvir

Comment in

PMID:
25977266
DOI:
10.1093/cid/civ381
[Indexed for MEDLINE]

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