CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

1 Hosp Univ de Valme, Sevilla, Spain, 2 Hosp Univ Reina Sofía, Córdoba, Spain, 3 Univ of Modena and Reggio Emilia, Modena, Italy, 4 Hosp de La Línea, La Línea de la Concepción, Spain, 5 Complejo Hospario Univ de Huelva, Huelva, Spain Background: Contradictory data about the impact of the rs738409 steatosis-related polymorphismwithin PNPLA3 gene on liver fibrosis progression in HIV/hepatitis C virus (HIV/ HCV)-coinfected patients have been reported. Our objective was to test whether this, and other polymorphisms previously related to fatty liver disease in HIV infection linked to SAMM50 or LPPR4 genes, influence liver fibrosis progression in HIV/HCV-coinfected individuals. Methods: 332 HIV/HCV-coinfected patients who consecutively attended four Spanish university hospitals from November 2011 to July 2013 were included. A liver stiffness cut-off of 14.6 kPa, as determined by transient elastography, was used to diagnose cirrhosis. Liver stiffness progression was studied in 171 individuals who had two available LS determinations without anti-HCV treatment between them. Moreover, 28 HIV/HCV-coinfected patients who underwent liver transplant, as well as, 19 non-cirrhotic coinfected individuals used as controls, were included in an additional study. Results: Only rs738409 was associated with cirrhosis: 45 (29.6%) of 152 G allele carriers versus 36 (20.0%) of 180 CC carriers showed cirrhosis (multivariate p=0.018; adjusted odds ratio=1.98; 95% confidence interval=1.12-3.50). Also, 21 (30.4%) of 69 G allele carriers versus 16 (15.7%) of 102 CC patients showed significant liver stiffness progression (adjusted p-value=0.015; adjusted odds ratio=2.89; 95% confidence interval=1.23-6.83). Finally, the proportion of rs738409_G allele carriers was significantly higher in transplanted individuals than in controls (p=0.044, odds ratio=3.43; 95% confidence interval=1.01-11.70). Conclusion: The rs738409 polymorphism is associated with liver fibrosis progression in HIV/HCV-coinfected patients. 533 FIB-4 CUTOFFS FOR PREDICTION OF LIVER-RELATED EVENTS IN HIV/HCV COINFECTION Leire Pérez Latorre 1 , Marisa Montes 2 , Miguel A. Von Wichmann 3 , Manuel Crespo 4 , Marta Montero 5 , Carmen Quereda 6 , María J. Téllez 7 , José M. Bellón 1 , Juan González-García 2 , Juan Berenguer 1 1 Hosp General Univ Gregorio Marañón, Madrid, Spain, 2 Hosp Univ La Paz, Madrid, Spain, 3 Hosp Univ Donostia, San Sebastián, Spain, 4 Complexo Hospario Univ de Vigo, Vigo, Pontevedra, Spain, 5 Hosp Univ y Politécnico La Fe, Valencia, Spain, 6 Hosp Ramon y Cajal, Madrid, Spain, 7 Hosp Clínico de San Carlos, Madrid, Spain Background: FIB-4 accurately predicts hepatic fibrosis and is better than liver biopsy as a predictor of clinical outcomes in HIV/HCV-coinfected patients. We designed this study to define clinically useful FIB-4 cutoffs for prediction of liver-related events (LRE) in coinfected patients. Methods: We analyzed HIV/HCV-coinfected patients with compensated liver disease and a baseline FIB-4 value in the GeSIDA 3603 cohort. The primary outcome was occurrence of LRE (decompensation or hepatocellular carcinoma, whichever occurred first). We used ROC curves to assess the diagnostic capacity of FIB-4 to predict LRE. As sustained viral response (SVR) or end-of-treatment response (ETR) modifies the natural history of hepatitis C, we selected patients without SVR or ETR during follow-up and randomly allocated them to an estimation cohort (EC) or a validation cohort (VC). First, we identified a cutoff value of FIB-4 to recognize patients who would not develop LRE. In order to estimate the hazard of LRE for values above the cutoff, we assessed the assumption of linearity between FIB-4 and the proportion of LRE and then assessed the hazard of LRE according to different FIB-4 values above the cutoff using the Fine and Gray proportional hazards model and taking into account death as a competing risk. Results: The study population comprised 657 patients (77%men, median age, 80% prior IDU, 34% advanced fibrosis). After a median follow-up of 5.4 years, 117 patients experienced an LRE, and 70 died. No significant differences in baseline characteristics or outcomes were detected between the EC (n=422) and VC (n=235). The AUROCs (95%CI) of FIB-4 for prediction of LRE in the EC and the VC were 0.77 and 0.79, respectively. Of all the possible values of FIB-4 in the EC ROC curves (min 0.44–max 16.61), we selected the cutoff of 1 with a negative predictive value of 96.9%. Per each unit of FIB-4 increase above 1 in the whole dataset (EC + VC), the sHR of LRE was 1.29 (95% CI: 1.21–1.38); P>0.001. The figure shows cumulative incidence plots of LRE for the various FIB-4 strata. Conclusion: We found that a FIB-4 value of 1 identified 2 populations at risk of developing LRE. We also found that the hazard of LRE increased proportionally with FIB-4 values above this cutoff. These findings support the role of FIB-4 in the assessment of prognosis in patients with HIV/HCV coinfection. FIB-4 could prove particularly attractive for care or research settings that do not have access to TE. 534 EFFECTIVENESS OF DAAs IN HIV/HCV-COINFECTED PATIENTS WITH DECOMPENSATED CIRRHOSIS Juan Berenguer 1 , Lourdes Domínguez-Domínguez 2 , Ángela Gil-Martín 3 , Carmen Quereda 4 , Teresa Aldámiz-Echevarría 1 , Ignacio Santos 5 , Pablo Ryan 6 , Gabriel Gaspar 7 , Inma Jarrin 8 , Juan Gonzalez-Garcia 9 1 Gregorio Maranon Hosp, Madrid, Spain, 2 Hosp Univ 12 de Octubre, Madrid, Spain, 3 Servicio Madrileño de Salud, Madrid, Spain, 4 Hosp Ramon y Cajal, Madrid, Spain, 5 Hosp Univ de La Princesa, Madrid, Spain, 6 Infanta Leonor Hosp, Madrid, Spain, 7 Hosp Univ de Getafe, Getafe, 28905, 8 Inst of Hlth Carlos III, Madrid, Spain, 9 Hosp Univ La Paz, Madrid, Spain Background: Clinical trials and real-life studies show high rates of success after all-oral therapy (Rx) with direct-acting antivirals (DAA) in HCV-monoinfected patients with decompensated cirrhosis (De-C). We assessed real-life outcomes of all-oral DAA Rx in HIV/HCV-coinfected patients with De-C. Methods: MADRID-CoRe is a prospective registry of coinfected adults receiving all-oral DAA in hospitals of the Madrid Regional Health Service (SERMAS). De-C was defined as current/prior Child-Turcotte-Pugh (CTP) stage B or C or current/prior liver decompensation or hepatocellular carcinoma (HCC). The primary endpoint was sustained viral response at week 12 (SVR12). Between Nov. 2014 and Aug. 2016, 2662 coinfected individuals in MADRID-CoRe initiated DAA. Of the 1953 patients who were scheduled to finish treatment on May 31, 2016, severity of liver disease was as follows: no cirrhosis (No-C), 1066 (54.58%); compensated cirrhosis (Co-C), 736 (37.69%); De-C, 146 (7.48%); and unknown, 5 (0.26%). Results: The main characteristics of the 146 patients with De-C were male sex, (102, 69.86%), median age of 51.58 yr., cART (125, 85.62%), and Rx-naïve (88, 60.27%). One patient had had a liver-transplant (LT), 7 were on the LT waiting list, and 15 had HCC. CTP scores were as follows: A, 75 (51.37%); B, 62 (42.47%); and C, 9 (6.16%). The HCV genotypes were G1a (49, 33.56%), G1b (32, 21.92%), G4 (30, 20.55%), G3 (22, 15.07%), and other (13, 8.90%). The DAA regimens were SOF/LDV (73), SOF+DCV (36), SOF+SMV (26), SOF+RBV (7), PrOD (3), and SMV+DCV (1). RBV was used in 69 patients (47.26%). SVR12 was achieved by 118 patients with De-C (80.82%). This figure was significantly lower than SVR12 achieved by patients with Co-C (91.17%) (P<.001) and patients with No-C (93.53%) (P<.001). The differences between Co-C and No-C were not statistically significant. Of the De-C patients without SVR12, 17 (11.64%) relapsed, 5 (3.42%) died, 2 (1.37%), stopped Rx owing to AE, 1 (0.68%) had breakthrough infection, and 3 (2.05%) stopped for other reasons. The variables associated with SVR12 in the multivariate logistic regression analysis are shown in the table. Conclusion: The SVR12 rate with all-oral DAAs in coinfected patients with De-C was 81%, ie, significantly lower than in patients with compensated liver disease. Male sex and CTP stage C were associated with treatment failure in De-C. The long-term impact of all-oral DAA Rx in HIV/HCV-coinfected patients with De-C remains to be determined. 535 EFFICACY AND SAFETY OF DAAs IN CIRRHOTIC HCV/HIV COINFECTED PATIENTS Jordi Navarro 1 , Montse Laguno 2 , Helem Haydee Vilchez 3 , Josep M. Guardiola 4 , Jose A. Carrion 5 , Luis Force 6 , Mireia Cairó 7 , Carmen Cifuentes 8 , Manuel Crespo 9 , for the Catalano- Balear Study Group 1 Hosp Univ Vall d’Hebron, Barcelona, Spain, 2 Hosp Clínic i Provincial de Barcelona, Barcelona, Spain, 3 Hosp Univ de Son Espases, Palma de Mallorca, Spain, 4 Hosp de la Santa Creu i Sant Pau, Barcelona, Spain, 5 Hosp del Mar, Barcelona, Spain, 6 Hosp de Mataró, Mataró, Spain, 7 Hosp Univ Mútua de Terrassa, Terrassa, Spain, 8 Hosp de Son Llàtzer, Palma de Mallorca, Spain, 9 Hosp Univ de la Vall d’Hebron, Barcelona, Spain Background: There is scarce data regarding efficacy and safety of new direct antiviral agents (DAA) in cirrhotic HCV-HIV coinfected patients. Methods: Multicenter prospective cohort analysis carried-out in 13 Spanish hospitals between January and December 2015. Inclusion criteria: 1) Cirrhosis diagnosed by transient elastography (TE>14.6KPa) or by sonographic, endoscopic and/or clinical data. 2) HCV-treatment based on DAA according to drug availability and physician discretion. 3) HCV-HIV coinfection with stable ART and controlled HIV infection. Primary endpoint: Overall efficacy, defined as the percentage of patients with undetectable HCV-RNA at week 12 after

Poster and Themed Discussion Abstracts

CROI 2017 223