Association of Sofosbuvir and Daclatasvir Plasma Trough Concentrations with Patient-, Treatment-, and Disease-Related Factors Among HIV/HCV-Coinfected Persons

Background Sofosbuvir plus daclatasvir achieves high rates of sustained virologic response (SVR), with no differences according to HIV serostatus. However, only limited information is available on the pharmacokinetic variability of sofosbuvir and daclatasvir in HIV/HCV-coinfected patients. Objective...
Ausführliche Beschreibung

Background Sofosbuvir plus daclatasvir achieves high rates of sustained virologic response (SVR), with no differences according to HIV serostatus. However, only limited information is available on the pharmacokinetic variability of sofosbuvir and daclatasvir in HIV/HCV-coinfected patients. Objectives The aim of this study was to identify patient-, treatment-, and disease-related factors that are significantly associated with sofosbuvir and daclatasvir plasma trough concentrations (Ctrough), including liver and renal function, among HIV/HCV-coinfected persons. Methods In this observational cohort pilot study, HIV/HCV-coinfected patients undergoing sofosbuvir plus daclatasvir treatment were prospectively enrolled. Biochemical and viro-immunological parameters were assessed at baseline, week 4 (W4), end of treatment (EOT), and after EOT. The FIB-4 score and CKD-EPI equation were used to estimate liver disease and glomerular filtration rate (eGFR), respectively. For sofosbuvir, sofosbuvir metabolite (GS-331007), and daclatasvir, Ctrough was measured at W4 and week 8 (W8), and the mean of the values at those two time points (mean-Ctrough) was calculated. The Mann–Whitney test and Spearman’s rank correlation were used to evaluate the correlations between the mean-Ctrough of each direct-acting antiviral (DAA) and the considered variables. Results Thirty-five patients were included (SVR 94%). An increased GS-331007 mean-Ctrough was significantly correlated with a decreased eGFR at W4 (rho = −0.36; p = 0.037) and EOT (rho = −0.34; p = 0.048). There was a significant correlation between daclatasvir mean-Ctrough and FIB-4 at all time points: baseline (rho = −0.35; p = 0.037), W4 (rho = −0.44; p = 0.008), EOT (rho = −0.40; p = 0.023), and after EOT (rho = −0.39; p = 0.028). Conclusions In HIV/HCV-coinfected patients in a real-world setting, exposure to a high GS-331007 Ctrough was associated with a slight decrease in renal function, while advanced hepatic impairment was significantly associated with a lower daclatasvir Ctrough. Though the clinical and therapeutic relevance of these findings may be limited, increasing clinicians’ knowledge regarding DAA exposure in difficult-to-treat patients could be relevant in single cases, and further investigations are warranted. Ausführliche Beschreibung

Autor*in:	Mastrorosa, Ilaria [verfasserIn] Tempestilli, Massimo Notari, Stefania Lorenzini, Patrizia Fabbri, Gabriele Grilli, Elisabetta Bellagamba, Rita Vergori, Alessandra Cicalini, Stefania Ammassari, Adriana Agrati, Chiara Antinori, Andrea

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Anmerkung:	© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2021

Übergeordnetes Werk:	Enthalten in: European journal of drug metabolism and pharmacokinetics - Cham : Springer Internat. Publ., 1976, 47(2021), 1 vom: 08. Okt., Seite 135-142
Übergeordnetes Werk:	volume:47 ; year:2021 ; number:1 ; day:08 ; month:10 ; pages:135-142

Links:	Volltext

DOI / URN:	10.1007/s13318-021-00725-w

Katalog-ID:	SPR04595321X