Author information
1
Internal Medicine Department, CHU de Nice, Hôpital Archet 1, Nice, France.
2
Pharmacology Department, CHU Rennes, Rennes, France.
3
Inserm, CIC1414, Rennes, France.
4
Pharmacology Laboratory, Faculté de Médecine, Univ Rennes 1, Rennes, France.
5
Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, Inserm, IRD, Aix Marseille Univ, Marseille, France.
6
Observatoire Régional de la Santé Provence-Alpes-Côte d'Azur, Marseille, France.
7
Clinical Pharmacology and Toxicology Department, CHU de Nice, Nice, France.
8
Infectious Diseases Department, APHP, Hôpital Bicêtre, Le Kremlin Bicêtre, France.
9
Infectious and Tropical Diseases Department, Hôpital de Perpignan, Perpignan, France.
10
Infectious Diseases Department, APHP, Hôpital Saint Antoine, Paris, France.
11
Hepatology Department, HCL, Hôpital de la Croix-Rousse, Lyon, France.
12
Infectious Diseases Department, CHU Nantes, Nantes, France.
13
Virology Department, APHP, Hôpital Henri Mondor, Créteil, France.
14
Clinical Immunology Department, APHP, Hôpital Henri Mondor, Créteil, France.
15
Infectious Diseases Department, APHP, Hôpital La Pitié Salpêtrière, Paris, France.
16
Infectious Diseases Department, CHU Montpellier, Montpellier, France.
17
Infectious Diseases Department, CHU de Nice, Hôpital Archet 1, Nice, France.
18
Infectious Diseases Department, HCL, Hôpital de la Croix-Rousse, Lyon, France.
19
Hepatogastroenterology Department, CHU Toulouse, Toulouse, France.
20
Hepatogastroenterology Department, CHU Grenoble, Grenoble, France.
21
Infectious Diseases Department, CHU Bordeaux, Bordeaux, France.
22
Hemato Oncology Department, CH du Pays d'Aix, Aix-en-Provence, France.
23
Infectious Diseases Department, APHP, Hôpital R Poincaré, Garches, France.
24
Infectious Diseases Department, APHP, Hôpital J Verdier, Bondy, France.
25
Infectious and Tropical Diseases Department, APHP, Hôpital Tenon, Paris, France.
26
Infectious Diseases Department, APHP, Hôpital Cochin, Paris, France.
27
Internal Medicine and Infectious Diseases Department, CHU Bordeaux, Bordeaux, France.
28
Infectious and Tropical Diseases Department, CHU Bordeaux, Bordeaux, France.
29
Internal Medicine Department, CHD Vendée, La Roche sur Yon, France.
30
Infectious Diseases Department, CHU Dijon, Dijon, France.
31
Hepato-Gastroenterology Department, APHP, Hôpital Cochin, Paris, France.
32
Hepatogastroenterology Department, Hôpital Saint Joseph, Marseille, France.
33
Hepatogastroenterology Department, CHU Montpellier, Montpellier, France.
34
Internal Medicine Department, CHU Toulouse, Toulouse, France.
35
Internal Medicine Department, Hôpital Foch, Suresne, France.
36
Immuno and Clinical Hematology department, APHM Sainte-Marguerite, Aix Marseille Univ, Marseille, France.
37
Inserm U912 (SESSTIM), Marseille, France.
38
Infectious and Tropical Diseases Department, APHP, Hôpital Bichat, Paris, France.
39
Unité de Recherche Clinique et Fondamentale sur les Hépatites Virales, ANRS (France Recherche Nord & Sud Sida-hiv Hépatites), Paris, France.
40
Hepatogastroenterology Department, APHP, Hôpital Saint Louis, Paris, France.
Abstract
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.