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)

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TitreEfficacy, 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)
Type de publicationJournal Article
Year of Publication2018
AuteursRosenthal E., Fougerou-Leurent C., Renault A., Carrieri M.P, Marcellin F., Garraffo R., Teicher E., Aumaitre H., Lacombe K., Bailly F., Billaud E., Chevaliez S., Dominguez S., Valantin M.A, Reynes J., Naqvi A., Cotte L., Metivier S., Leroy V., Dupon M., Allegre T., De Truchis P., Jeantils V., Chas J., Salmon-Ceron D., Morlat P., Neau D., Perre P., Piroth L., Pol S., Bourliere M., Pageaux G.P, Alric L., Zucman D., Girard P.M, Poizot-Martin I., Yazdanpanah Y., Raffi F., Le Pabic E., Tual C., Pailhe A., Amri I., Bellissant E., Molina J.M, Grp ANRSHC31 SOFTR
JournalHIV MEDICINE
Volume19
Pagination227-237
Date PublishedMAR
Type of ArticleArticle
ISSN1464-2662
Mots-cléscoinfection, Hepatitis C virus, HIV, ledipasvir, Sofosbuvir, treatment
Résumé

ObjectivesStudies 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-naive patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment-experienced patients with and without cirrhosis. MethodsWe 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. ResultsOf 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. ConclusionsLDV/SOF provided a high SVR rate in PI-experienced subjects coinfected with HCV genotype 1 and HIV-1, including patients with cirrhosis.
DOI10.1111/hiv.12571