CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

717

Predictors of Liver-Related Events Following DAA HCV Cure in PWH With Advanced Fibrosis/Cirrhosis Juan Berenguer 1 , Teresa Aldámiz-Echevarría 1 , Víctor Hontañón 2 , Chiara Fanciulli 1 , Carmen Quereda 3 , Carmen Busca 2 , Lourdes Domínguez 4 , Cristina Hernández 5 , Jorge Vergas 6 , Lucio J. García-Fraile 7 , Marta De Miguel 8 , Cristina Díez 1 , José M. Bellón 1 , Juan González-García 2 , for the GeSIDA 10318 -MARATHON Study Team 1 Hospital General Universitario Gregorio Marañón, Madrid, Spain, 2 La Paz University Hospital, Madrid, Spain, 3 Hospital Ramón y Cajal, Madrid, Spain, 4 Hospital Universitario 12 de Octubre, Madrid, Spain, 5 Hospital Universitario Príncipe de Asturias, Madrid, Spain, 6 Hospital Universitario Clí¬nico San Carlos, Madrid, Spain, 7 Hospital Universitario de La Princesa, Madrid, Spain, 8 Fundación SEIMC GeSIDA, Madrid, Spain Background: We assessed prognostic factors of liver-related events (LRE) among HCV-coinfected PWH with advanced fibrosis (AF) or compensated cirrhosis (CC) with SVR following all-oral direct antiviral therapy (DAA-Rx). Methods: We leveraged 3 prospective observational studies in Spain to select coinfected PWH with AF (biopsy confirmed F3 or liver stiffness [LS] value > 9.9 and ≤ 12.5 kPa) or CC (biopsy confirmed or LS > 12.5 kPa) with SVR following DAA-Rx from 2014 to 2017. The primary outcome was an LRE: decompensation (DEC) or hepatocellular carcinoma (HCC), whichever occurred first after the finalization of DAA therapy. Independent variables (based on the underlying conceptual framework) included liver disease category, age, sex, smoking, alcohol abuse, methadone use, prior clinical AIDS, CD4+ T-cell count, albumin concentration, metabolic syndrome, TyG and HSI indexes, and values of LS and FIB4 at baseline and 1 year after finalization of DAA therapy (1-yr). Multivariable competing-risk regression analyses with multiple imputations by chained equations for missing data were used to assess the effect of the independent variables on the outcomes. We used ROC curves to determine the diagnostic capacity of LS to predict LRE with the selection of the optimum cutoff value according to Youden's J statistic. Results: 1,145 PWH (384 AF and 761 CC) were included. After a median follow up of 41 months, 60 patients died, 24 had DEC, and 21 developed HCC. The risk of LRE was higher among those with CC than those with AF, but no statistically significant differences in overall and cause-specific mortality were found between groups. Albumin concentration (aSHR [95% CI] 0.55 [0.35 – 0.87]) per g/L increase) and 1-yr LS values (aSHR [95% CI] 1.04 [1.01 – 1.09] per kPa increase) were the only factors independently associated with the risk of LRE. The best cutoff value of 1-yr LS to predict LRE was 12.5 kPa (NPV: 99.5% [95% CI: 98.2 – 99.9]). For each 5 kPa increase above this cutoff, the HR of LRE was 1.34 (95% CI, 1.24 – 1.45). When we took the 12.5 kPa cutoff as the reference, the HR of LRE in patients with LS values of 12.5-24.9 kPa and ≥ 25 kPa were 11.45 (95% CI, 2.48 – 52.82) and 26.49 (95% CI, 5.79 – 121-22) respectively (Figure). Conclusion: Albumin concentration and 1-yr LS values after the finalization of a successful DAA therapy were identified as independent predictors of LRE among HCV-coinfected PWH with AF or CC. The best cutoff value of 1-yr LS to predict LRE was 12.5 kPa.

718

Immunophenotypic Profile Modifications After Spontaneous HCV Clearance or DAA Treatment in PWHIV Camille Jacqueline 1 , Violeta Lara Aguilar 1 , Manuel Llamas-Adán 1 , Cristina González Díaz 1 , Sergio Grande-García 1 , Celia Crespo-Bermejo 1 , Sonia Arca Lafuente 1 , Luz Martín-Carbonero 2 , Pablo Ryan 3 , Ignacio De los Santos 4 , Verónica Briz 1 , Amanda Fernández-Rodíguez 1 1 Institute of Health Carlos III, Madrid, Spain, 2 Hospital La Paz Institute for Health Research, Madrid, Spain, 3 Hospital Universitario Infanta Leonor, Madrid, Spain, 4 Hospital Universitario de La Princesa, Madrid, Spain Background: Acquisition of HCV is frequent among people with HIV (PWHIV), an event that profoundly modifies the natural history of both infections. Our goal was to analyze whether HCV clearance by direct-acting antivirals (DAAs) after chronic infection can partially restore both molecular and cellular immune profile to levels similar to those found in PWHIV. In addition, we explored whether changes over time in these patients were similar to those found in patients who cleared HCV spontaneously after acute infection. Methods: We performed a longitudinal observational study in 88 PWHIV: i) 31 with active chronic HCV infection (CHC) prior to starting DAA therapy and 48 weeks after achieving sustained virological response (SVR); ii) 25 who previously cleared HCV spontaneously (AE); iii) 32 controls (HIV) never infected with HCV. Both AE and HIV also were follow-up 48 weeks after first sample. A total of 27 CD4+ and CD8+ peripheral T cell subsets were assessed by spectral flow cytometry (18 antibodies) as well as 73 plasma molecules by multiplex immunoassay (Luminex, procartaplex). Differences in cell populations and plasma molecules were assessed by generalized linear models adjusted for the most significant clinical variables and multiple comparisons (p-value corrected by Benjamin-Hochberg (q<0.15). Results: At follow-up, lower levels of senescence markers (PD1, CD57) and central memory (CD3+CD4+or CD8+CD45RA-CCR7+CD27+CD28+) and naïve (CD3+CD4+or CD8+CD45RA+CCR7+CD27+CD28+) CD4+ and CD8+ T cells were observed in the CHC group compared to control. On the other hand, the AE group showed an increase in exhausted immune cells and immunosenescence markers over time to levels similar to those of HIV+ control patients. Also, AE group showed a higher level of effector memory CD4+ and CD8+ T cells (EM:CD45RA-CCR7-; EM_TH01: CD45RA-CCR7-CD28+CD27+; EM_TH1: CD45RA-CCR7-CD28-CD27-; EM _TH12: CD45RA-CCR7-CD28+CD27-) than HIV. The immune profile of the CHC and AE groups were very similar at follow-up. Regarding plasma molecules, 48 weeks after achieving SVR, a decrease in proinflammatory cytokines, checkpoint inhibitors and immune cell activation was observed compared to values before initiation of DAAs therapy. Conclusion: Clearance with DAAs after chronic HCV infection improved cellular senescence profile but remained higher than controls. The slightly higher levels of circulating immunosenescence markers after 1-year follow-up in the AE group may indicate possible accelerated aging driven by acute HCV infection. Influence of Markers Related to Biological Aging on Liver Regeneration in HCV Patients Achieving SVR Alejandro González-Serna 1 , Anais Corma-Gomez 2 , Chiara Del Pietro 1 , Mercedes Cano 1 , Marta Santos 2 , Carmen Martín-Sierra 2 , Pilar Rincón 2 , Juan Antonio Pineda 3 , Luis M Real 1 , Juan Macias 1 1 University of Sevilla, Sevilla, Spain, 2 Hospital Universitario de Valme, Seville, Spain, 3 University of Sevilla, Seville, Spain

Poster Abstracts

719

CROI 2024 211