CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Methods: From a prospective multicohort study, patients who completed a course of currently recommended DAA-based therapy at 33 Spanish hospitals and who had reached SVR12 evaluation timepoint were selected. Treatment week 4 HCV-RNA levels were categorized in target not detected (TND), below the lower limit of quantitation (LLOQTD) and ≥LLOQ. Results: A total of 818 patients were included. SVR12 rates [n/N (%)] for HCV genotypes 1a, 1b, 3 and 4 in an on-treatment approach were 275/282 (97.5%), 283/286 (99%), 114/123 (92.7%) and 123/127 (94.5%). Of the HCV genotype 3-infected patients, 86 (70%) received sofosbuvir/daclatasvir+/-ribavirin, 27 (22%) sofosbuvir/ledipasvir/ribavirin and 10 (8.1%) sofosbuvir/ribavirin, respectively. In this subgroup, in those that achieved TND, LLOQTD and ≥LLOQ, SVR12 was 81 (97.6%), 24 (85.7%) and 9 (75%), respectively; p (linear association)=0.001. Corresponding numbers for HCV genotype 3-infected subjects with cirrhosis were: 52 (96.3%), 14 (77.8%) and 7 (70%); p=0.004. There was no association between response at week 4 and SVR12 for the other HCV genotypes. Conclusion: Treatment week 4-response indicates the probability to achieve SVR12 to currently used DAA-based therapy in HCV genotype 3-infected individuals. This finding may be useful to tailor treatment strategy in this setting. 571 ALL ORAL DAA THERAPY IN HCV GENOTYPE 4 INFECTION WITH AND WITHOUT HIV COINFECTION Juan A. Pineda 1 , Luis E. Morano-Amado 2 , Francisco Téllez 3 , Blanca Figueruela López 4 , Marcial Delgado-Fernández 5 , Antonio Rivero-Juárez 6 , Dolores Merino 7 , Montserrat Pérez- Pérez 8 , Karin Neukam 1 , for the GEHEP-MONO/ HEPAVIR-DAA, RIS-HEP07 and RIS-HEP13 Study Groups 1 Hosp Univ de Valme, Sevilla, Spain, 2 Hosp Univ Alvaro Cunqueiro, Vigo, Spain, 3 Hosp de La Línea, La Línea de la Concepción, Spain, 4 Hosp Univ de Valme, Seville, Spain, 5 Hosp Regional Univ de Málaga, Málaga, Spain, 6 Hosp Univ Reina Sofía, Córdoba, Spain, 7 Complejo Hospario Univ de Huelva, Huelva, Spain, 8 Hosp La Línea, AGS Campo de Gibraltar, La Linea de la Concepcion, Spain Background: Data on the efficacy of all-oral interferon free combinations in patients with HCV genotype 4 (GT4) infection in real life are scarce, particularly in HIV/HCV-coinfected subjects. The efficacy of direct-acting antiviral (DAA) combinations in HCV-monoinfected and HIV/HCV-coinfected patients with in routine clinical practice is analyzed here. Methods: Two hundred and fifty-nine, 89 HCV-monoinfected and 170 HIV/HCV-coinfected, subjects harboring GT4 were analyzed. All of them completed a treatment including two DAA with or without ribavirin. Sustained virological response at week 12 of follow-up (SVR) was analyzed on an intention-to-treat basis. Results: One hundred and fifty-eight (93%) HIV/HCV-coinfected patients and 84 (94%) HCV-monoinfected subjects achieved SVR (p=0.657). Patients with cirrhosis (115 out of 128 [90%], p=0.021), those harboring IL28B genotype TT (22 out of 26 [85%], p=0.05) and those showing baseline plasma LDL-cholesterol ≤ 80 mg/dL (91 out of 100 [90%], p=0.013) responded worse. The impact of IL28B genotype was mainly seen in subjects with HIV coinfection (79% in patients with genotype TT and 94% among those with genotype non-TT [p=0.035] achieved SVR) and in individuals without cirrhosis (SVR 86% in genotype TT versus 100% among those with CC or CT [p=0.002]). Conclusion: The rate of SVR in HCV GT4 carriers treated with all-oral DAA combinations in real life is similar as in clinical trials, both in HCV-monoinfected and in HIV/HCV- coinfected patients. The response seems to be poorer in patients with cirrhosis and in those with IL28B genotype TT. These parameters could be used to tailor this therapy. 572 EFFECTIVENESS OF ALL-ORAL DAAs FOR HCV GENOTYPE 3 IN HIV/HCV-COINFECTED PATIENTS Juan González-García 1 , Ana Moreno 2 , Encarnnnacion Cruz 3 , Lourdes Domínguez-Domínguez 4 , Victoria Moreno 1 , Jorge Vergas 5 , Jose Sanz 6 , Laura Benitez 7 , Beatriz Álvarez 8 , Juan Berenguer 9 1 Hosp Univ La Paz, Madrid, Spain, 2 Hosp Ramon y Cajal, Madrid, Spain, 3 Subdireccion General de Farmacia, Madrid, Spain, 4 Hosp Univ 12 de Octubre, Madrid, Spain, 5 Hosp Clinico San Carlos, Madrid, Spain, 6 Hosp Príncipe de Asturias, Alcalá de Henares (Madrid), Spain, 7 Clinica Puerta de Hierro, Majadahonda (Madrid), Spain, 8 Hosp Univ Fundación Jiménez Díaz, Madrid, Spain, 9 Hosp General Univ Gregorio Marañón, Madrid, Spain Background: Infection with HCV genotype 3 (GT3) is common among HIV/HCV-coinfected patients and has more frequently been associated with an increased risk of progression to cirrhosis and development of steatosis or hepatocellular carcinoma than other HCV genotypes. GT3 is currently the most difficult genotype to treat, with fewer therapeutic options based on all-oral direct-acting antivirals (DAAs) than other genotypes. Our aimwas to evaluate treatment outcomes of DAA regimens for HIV/HCV-coinfected patients with GT3 and compensated liver disease. Methods: The Madrid coinfection registry (MADRID-CoRe) is a prospective registry of all coinfected adults (≥18 years) undergoing DAA therapy for HCV in hospitals from the Madrid Regional Health Service (SERMAS). We assessed sustained viral response at week 12 (SVR12), viral relapse, and failure due to treatment discontinuation. Between November 2014 and August 2016, 2662 HIV/HCV-coinfected individuals in MADRID-CoRe initiated DAAs. Here, we present data from HIV/HCV-coinfected patients with GT3 and compensated liver disease who were scheduled to complete treatment on May 31, 2016. Results: We evaluated 273 patients who met the inclusion criteria. The DAA regimens were as follows: a) daclatasvir/sofosbuvir 196 patients (106 not taking ribavirin [8 wk, 1; 12 wk, 84; 16 wk, 2; 24 wk, 19], and 90 taking ribavirin [12 wk, 43; 16 wk, 1; 24 wk, 46]. B) ledipasvir/sofosbuvir 73 patients (11 not taking ribavirin for 24 wk, and 62 taking ribavirin [12 wk, 5; 24 wk, 57]). C) sofosbuvir/ribavirin for 24 wk, 4 patients. Two patients treated with sofosbuvir/ribavirin achieved SVR12, and 2 discontinued therapy. Patient characteristics and treatment outcomes for daclatasvir/sofosbuvir and ledipasvir/sofosbuvir are shown in the table. Conclusion: We found daclatasvir/sofosbuvir to be highly effective in HIV/HCV-coinfected patients with GT3 with or without cirrhosis, thus confirming the results of clinical trials. Ledipasvir/sofosbuvir was also highly effective in a particularly difficult-to-treat population composed mainly of patients with liver cirrhosis and very high liver stiffness values. The small sample size precludes any conclusion about the effectiveness of sofosbuvir/ribavirin. 573 SOFOSBUVIR/LEDIPASVIR AS CHOLESTEROL-INCREASE RISK FACTOR IN HIV SUBJECTS Mario Frías , Antonio Rivero-Juárez, Francisca Cuenca-Lopez, Angela Camacho-Espejo, Diego Rodriguez-Cano, Pedro Lopez-Lopez, Teresa Brieva, Antonio Rivero Hosp Univ Reina Sofia, Cordoba, Spain Background: Although HCV viral clearance is clearly linked to a lipid metabolic restoration, could exists other factors which have a direct impact on LDL-cholesterol, regardless of viral suppression. Thus, the objective of our study was to evaluate risk factors associated with serum cholesterol levels increase during IFN-free HCV therapy. Methods: Prospective, longitudinal study where HIV-infected patients who started and completed a IFN-free therapy for chronic HCV genotype 1 or 4 infection were included. Patients were treated using two different regimens: i) Sofosbuvir + Ledipasvir (SOF/LDV) with/without ribavirin (RBV), or ii) Paritaprevir + Ombitasvir bosted with ritonavir and Dasabuvir (PRT/OMV/rtv/DSB) with/without RBV. In all patients total, HDL and LDL cholesterol, was measured at baseline and at weeks 1, 2, 4, 8 and end of treatment. The changes of cholesterol levels at each week compared with baseline were calculated. Results: A total of 129 patients completed a full course of therapy and constituted the study population. Of them, 67 (51.9%) initiated therapy with SOF/LDV, 47 (36.4%) with PRT/ OMV/rtv/DSB, and 15 (11.6%) with PRT/OMV/rtv. An increase on both total and LDL cholesterol was observed in the overall population at all weeks of therapy. Use of SOF/LDV was associated with both total and LDL cholesterol increase at each time point (Figure 1A and Figure 1B). This effect of SOF/LDV on total and LDL cholesterol was observed in all HCV genotypes, compared with patients receiving PRT/OMV/rtv/DSB. In the linear multivariate analysis, use of SOF/LDV was identified as an associated factor with increasing on both total and LDL cholesterol, adjusted by sex, liver cirrhosis, HCV-viral decline, HIV co-infection, HCV-genotype, and hypolipemiant treatment use. Conclusion: Our study shows that SOF/LDV increase LDL cholesterol levels during HCV therapy as early as the first week of treatment. Interestingly, this observation was independent of HCV viral clearance, suggesting a direct effect of this combination on LDL cholesterol increase. The clinical impact of this association, overall in high risk cardiovascular patients should be evaluate.

Poster and Themed Discussion Abstracts

CROI 2017 241