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)
Authors: E Rosenthal
Antoine Cheret
Laurence G√©rard
L Alric
Julie Raimon
I Poizot-Martin
J Reynes
V Jeantils
S Metivier
A Pailh√©
D Salmon-Ceron
Alain Lafeuillade
P De Truchis
Y Yazdanpanah
Djamila Makhloufi
Thierry May
M A Valantin
E Billaud
E Le Pabic
G P Pageaux
H Aumaitre
L Cotte
D Zucman
M P Carrieri
M Dupon
M Bourli√®re
Emmanuel Mortier
C Fougerou-Leurent
T Allegre
Jacques Moreau
Anne Simon
A Naqvi
D Neau
Victor de Ledinghen
J M Molina
F Raffi
K Lacombe
P Perr√©
ANRS HC31 SOFTRIH Study Group
V Leroy
J Chas
S Pol
E Teicher
R√©gine Thierry
Christian Michelet
F Bailly
Mustapha Ahmim
P Morlat
Isabelle Rosa
F Marcellin
S Chevaliez
E Bellissant
S Dominguez
L Piroth
Claudine Duvivier
Dominique Batisse
Am√©lie Martin
P M Girard
C Tual
R Garraffo
I Amri
A Renault
Journal: HIV Medicine (2018)
Discipline: IMMUNOLOGY
Keywords: HIV; coinfection; hepatitis C virus; ledipasvir; sofosbuvir
Affiliations: Internal Medicine Department, CHU de Nice, H√¥pital Archet 1, Nice, France., Pharmacology Department, CHU Rennes, Rennes, France., Inserm, CIC1414, Rennes, France., Pharmacology Laboratory, Facult√© de M√©decine, Univ Rennes 1, Rennes, France., Sciences Economiques & Sociales de la Sant√© & Traitement de l'Information M√©dicale, Inserm, IRD, Aix Marseille Univ, Marseille, France., Observatoire R√©gional de la Sant√© Provence-Alpes-C√¥te d'Azur, Marseille, France., Clinical Pharmacology and Toxicology Department, CHU de Nice, Nice, France., Infectious Diseases Department, APHP, H√¥pital Bic√™tre, Le Kremlin Bic√™tre, France., Infectious and Tropical Diseases Department, H√¥pital de Perpignan, Perpignan, France., Infectious Diseases Department, APHP, H√¥pital Saint Antoine, Paris, France., Hepatology Department, HCL, H√¥pital de la Croix-Rousse, Lyon, France., Infectious Diseases Department, CHU Nantes, Nantes, France., Virology Department, APHP, H√¥pital Henri Mondor, Cr√©teil, France., Clinical Immunology Department, APHP, H√¥pital Henri Mondor, Cr√©teil, France., Infectious Diseases Department, APHP, H√¥pital La Piti√© Salp√™tri√®re, Paris, France., Infectious Diseases Department, CHU Montpellier, Montpellier, France., Infectious Diseases Department, CHU de Nice, H√¥pital Archet 1, Nice, France., Infectious Diseases Department, HCL, H√¥pital de la Croix-Rousse, Lyon, France., Hepatogastroenterology Department, CHU Toulouse, Toulouse, France., Hepatogastroenterology Department, CHU Grenoble, Grenoble, France., Infectious Diseases Department, CHU Bordeaux, Bordeaux, France., Hemato Oncology Department, CH du Pays d'Aix, Aix-en-Provence, France., Infectious Diseases Department, APHP, H√¥pital R Poincar√©, Garches, France., Infectious Diseases Department, APHP, H√¥pital J Verdier, Bondy, France., Infectious and Tropical Diseases Department, APHP, H√¥pital Tenon, Paris, France., Infectious Diseases Department, APHP, H√¥pital Cochin, Paris, France., Internal Medicine and Infectious Diseases Department, CHU Bordeaux, Bordeaux, France., Infectious and Tropical Diseases Department, CHU Bordeaux, Bordeaux, France., Internal Medicine Department, CHD Vend√©e, La Roche sur Yon, France., Infectious Diseases Department, CHU Dijon, Dijon, France., Hepato-Gastroenterology Department, APHP, H√¥pital Cochin, Paris, France., Hepatogastroenterology Department, H√¥pital Saint Joseph, Marseille, France., Hepatogastroenterology Department, CHU Montpellier, Montpellier, France., Internal Medicine Department, CHU Toulouse, Toulouse, France., Internal Medicine Department, H√¥pital Foch, Suresne, France., Immuno and Clinical Hematology department, APHM Sainte-Marguerite, Aix Marseille Univ, Marseille, France., Inserm U912 (SESSTIM), Marseille, France., Infectious and Tropical Diseases Department, APHP, H√¥pital Bichat, Paris, France., Unit√© de Recherche Clinique et Fondamentale sur les H√©patites Virales, ANRS (France Recherche Nord & Sud Sida-hiv H√©patites), Paris, France., Hepatogastroenterology Department, APHP, H√¥pital 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-na√Øve 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 &lt; 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. 

Retracted: No

PubPeer comments:
 In this article Y Yazdanpanah and K Lacombe did not declare any competing interests. However they have some.   , 
 Eric: Could you explain what those conflicts are? ,