CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Methods: This is a multi-center observational real-life study of patients (pts) undergoing HCV retreatment after 1st generation-PI + peg-IFN and ribavirin (RBV) failure. Sustained virological response (SVR) was evaluated at week-12 of follow-up. HCV genotypic resistance testing (GRT) was performed by Sanger-based home made protocols. Results: 121 pts with chronic HCV infection (GT1b=57%; cirrhosis=87%) were retreated after a median (IQR) of 102 (74-123) weeks from a previous PI failure (telaprevir=69, boceprevir=51, simeprevir=1). Retreatment followed different strategies: A) 18 pts were treated with a GRT-based PI- or NS5A-containing regimen; B) 72 pts were treated with a “switch” regimen of sofosbuvir+NS5A inhibitor+RBV, without baseline GRT, following international guidelines; C) 31 pts received different regimens +/- RBV, neither recommended nor GRT-guided (see figure). Overall SVR rate was 91%, with differences according to strategy choice A), B) or C). All 18 pts treated with GRT-guided regimens (A) reached SVR (100%), despite heterogeneity in treatment duration, PI-inclusion (where indicted by GRT) and RBV use. 68/72 pts (94%) receiving a 2nd line regimen according to guidelines (B) achieved SVR; only 1/4 failing pts was a posteriori tested for natural RASs, revealing a natural L28M NS5A-RAS. On the contrary, SVR rate was strongly reduced (77%) among the 31 pts who received C) (a not recommended, not GRT-guided regimen) (p-trend<0.01). Overall, 37/121 pts were re-treated with a PI (simeprevir or paritaprevir) and 33/37 (90%) achieved SVR. The 4 failing GT-1a cirrhotic patients (all in option C) used a simeprevir-containing regimen; 3/4 showed a posteriori R155K NS3-RAS at baseline (1 had no baseline GRT). All 7 patients treated with a paritaprevir-containing regimen reached SVR, regardless treatment duration and performance of a baseline GRT. When GRT was available both at baseline and at 2nd failure, all pts showed an increase of RASs at the new failure. Conclusion: DAA’s retreatment after 1st generation PI failure can induce a maximal SVR rate if guided by GRT, greater than SOF+NS5A inhibitors+RBV for 24 weeks, as recommended by guidelines. PIs can be fruitfully reconsidered if appropriately chosen after a punctual GRT-based RASs evaluation.

Poster and Themed Discussion Abstracts

566 RETREATMENT OPTIONS AFTER FAILING A FIRST LINE OF DAAs AGAINST HEPATITIS C VIRUS Ana B. Perez 1 , Natalia Chueca 1 , Miguel García-Deltoro 2 , Ana María Martínez-Sapiña 3 , Daniel Navarro 4 , Dolores Merino 5 , Miguel Jiménez 6 , Juan Manuel Pascasio 7 , Antonio Rivero 8 , Federico García 1 1 Complejo Hospario Univ de Granada, Granada, Spain, 2 Hosp General de Valencia, Valencia, Spain, 3 Hosp Univ Miguel Servet, Zaragoza, Spain, 4 Complejo Hospario Univ de Santiago, Santiago de Compostela, Spain, 5 Complejo Hospario Univ de Huelva, Huelva, Spain, 6 Hosp Regional Carlos Haya, Málaga, Spain, 7 Hosp Univ Virgen del Rocío, Sevilla, Spain, 8 Hosp Univ Reina Sofia, Cordoba, Spain Background: In Spain, the rollout of interferon-free treatment of HCV infected patients has been implemented since April 2015. In our study, we evluated the retreatment options in a large cohort of patients failing IFN-free direct antiviral agents (DAAs) regimens in Spain (HCVREsp), and the prevalence of HCV resistance associated substitutions (RAS) Methods: HCVREsp is a prospective multicenter real world cohort enrolling HCV infected patients treated with IFN-free DAA regimens at discretion of the investigators. For patients failing their DAA regimen, population-based sequencing of HCV NS3, NS5A and NS5B genes was performed. When available, a baseline serum sample was analyzed in parallel. Ultra-deep sequencing in NS5B was performed to study mixed infections and to discriminate reinfection from relapse. Results: HCVREsp includes 5439 patients across Spain, 16.6% treated with SOF/SIM, 16.8%with SOF/DCV, 41.4%with SOF/LD, and 24.5%with Paritaprevir/Ombitasvir/Dasabuvir (3D). We present the data of 255 failing patients, 83%males, median age 53 (IQR 48-58), median log viral load 5,94 logs, IQR 5,49-6,46. Table 1 shows the frequency and characteristics of RAS in the failing cohort. Discordant genotyping from baseline data was observed in 35/255 (13,7%) patients; 4 cases of reinfection and 6 genotyping errors by the commercial methods used at origin were recorded. Conclusion: In this large Spanish HCV Resistance cohort genotypes 3 & 4 were less prone to the development of RAS, especially GT3 infected patients failing the SOF/LDV combination. Discordant genotype call was a frequent event, and mixed infections and intra- and inter- subtype/genotype reinfection also occurred. From the virological perspective, the recently approved Sofosbuvir-Velaptasvir regimen could be used to retreat a higher number of patients.

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