Efficacy, safety and patient-reported outcomes of ledipasvir/sofosbuvir in NS3/4A protease inhibitor-experienced individuals with hepatitis C virus genotype 1 and HIV coinfection with and without cirrhosis (ANRS HC31 SOFTRIH study) - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue HIV Medicine Année : 2018

Efficacy, safety and patient-reported outcomes of ledipasvir/sofosbuvir in NS3/4A protease inhibitor-experienced individuals with hepatitis C virus genotype 1 and HIV coinfection with and without cirrhosis (ANRS HC31 SOFTRIH study)

1 CHU Nice - Centre Hospitalier Universitaire de Nice
2 CIC - Centre d'Investigation Clinique [Rennes]
3 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
4 UR Médecine - Université de Rennes - Faculté de Médecine
5 ORS PACA
6 SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD - Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale
7 Hôpital Bicêtre
8 Centre Hospitalier Saint Jean de Perpignan
9 CHU Saint-Antoine [AP-HP]
10 HCL - Hospices Civils de Lyon
11 CHU Nantes - Centre Hospitalier Universitaire de Nantes
12 Hôpital Henri Mondor
13 CHU Pitié-Salpêtrière [AP-HP]
14 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
15 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
16 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
17 CHU Bordeaux
18 Centre Hospitalier du Pays d'Aix
19 Hôpital Raymond Poincaré [AP-HP]
20 Hôpital Jean Verdier [AP-HP]
21 CHU Tenon [AP-HP]
22 Hôpital Cochin [AP-HP]
23 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
24 Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin]
25 CHD Vendée - Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon
26 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
27 AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris]
28 Service d'hépatologie médicale [CHU Cochin]
29 Service de Gastro-entérologie [CHU Cochin]
30 Hôpital Saint-Joseph [Marseille]
31 Hôpital Foch [Suresnes]
32 Hôpitaux Sud - Hôpital Sainte-Marguerite [CHU - APHM]
33 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
34 ANRS France Recherche Nord & sud Sida-hiv hépatites
35 Hôpital Saint-Louis
E. Rosenthal
  • Fonction : Auteur correspondant
E. Teicher
  • Fonction : Auteur
L Cotte
  • Fonction : Auteur
M. Dupon
  • Fonction : Auteur
J Chas
  • Fonction : Auteur
P Morlat
  • Fonction : Auteur
D Neau
  • Fonction : Auteur
Laurent Alric
  • Fonction : Auteur
  • PersonId : 881462

Résumé

Objectives - Studies evaluating the efficacy and safety of the fixed-dose combination ledipasvir (LDV)/sofosbuvir (SOF) in patients coinfected with HIV-1 and hepatitis C virus (HCV) have mainly included treatment-naïve patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment-experienced patients with and without cirrhosis.Methods - We conducted a multicentre, open-label, double-arm, nonrandomized study in patients coinfected with HIV-1 and HCV genotype 1 with and without cirrhosis, who had good viral suppression on their antiretroviral regimens. All patients were pretreated with a first-generation NS3/4A protease inhibitor (PI) plus pegylated interferon/ribavirin. Patients received a fixed-dose combination of LDV/SOF for 12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a sustained virological response (SVR) 12 weeks after the end of therapy. Secondary endpoints included safety, pharmacokinetics and patient-reported outcomes.Results - Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty-five patients [95.6%; 95% confidence interval (CI): 87.6-99.1%; P < 0.0001] achieved an SVR, with similar rates of SVR in those with and without cirrhosis. Tolerance was satisfactory, with mainly grade 1 or 2 adverse events. Among patient-reported outcomes, only fatigue significantly decreased at the end of treatment compared with baseline [odds ratio (OR): 0.36; 95% CI: 0.14-0.96; P = 0.04]. Mean tenofovir area under the plasma concentration-time curve (AUC) at week 4 was high, with mean ± SD AUC variation between baseline and week 4 higher in cirrhotic than in noncirrhotic patients (3261.57 ± 1920.47 ng/mL vs. 1576.15 ± 911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%), hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia (13.2%) were reported. The serum creatinine level was not modified.Conclusions - LDV/SOF provided a high SVR rate in PI-experienced subjects coinfected with HCV genotype 1 and HIV-1, including patients with cirrhosis.
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Dates et versions

hal-01740817 , version 1 (17-10-2018)

Identifiants

Citer

E. Rosenthal, C Fougerou-Leurent, A. Renault, Mp. Carrieri, F. Marcellin, et al.. Efficacy, safety and patient-reported outcomes of ledipasvir/sofosbuvir in NS3/4A protease inhibitor-experienced individuals with hepatitis C virus genotype 1 and HIV coinfection with and without cirrhosis (ANRS HC31 SOFTRIH study). HIV Medicine, 2018, 19 (3), pp.227-237. ⟨10.1111/hiv.12571⟩. ⟨hal-01740817⟩
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