CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

inflammation and cognitive impairment in coinfection would be decreased after HCV SVR. Methods: We studied 41 participants before and after treatment for HCV alone or with viral controlled HIV coinfection. We measured monocyte activation and gene expression, plasma inflammation and cognitive impairment. Monocyte- derived exosomal miRNAs were studied with RNA sequencing before treatment and followed by qRT-PCR after SVR. Results: All HCV-coinfected subjects achieved SVR but one. Blood CD16+ monocytes were significantly decreased in coinfection after HCV treatment. Plasma sCD163 and neopterin were also decreased in HCV mono and coinfected persons. Overall cognition improved 25% in coinfection with visual learning/ memory the most improved. HCV SVR decreased monocyte interferon genes MX1, IFI27 and CD169 in coinfection and MX1, LGALS3BP and TNFAIP6 in HCV monoinfection. CD83, IL6 and CXCL10 monocyte gene expression correlated with cognitive impairment before therapy; only CXCL10 continued to correlate with impairment and specifically worsening executive function and attention deficits despite DAA therapy. Monocyte exosomes from coinfected persons after treatment were significantly increased in miR-19a, miR-221 and marginally miR-223, all associated with decreasing inflammation and NF-κB activation. Conclusion: HCV SVR in coinfection brings monocyte activation markers to levels seen with HIV alone. Cognitive impairment is significantly improved with HCV cure but not better than HIV infection alone strongly suggesting that cognitive impairment was driven by both HIV and HCV. Previous reports on the high percentage of cognitive impairment in HIV may have been greatly influenced by HCV coinfection. 585 TELOMERE LENGTH OF CIRRHOTIC HIV/HCV PATIENTS INCREASES AFTER HCV CLEARANCE WITH DAAS Silvia S. Molina Carrión 1 , Óscar Brochado Kith 1 , Juan González-García 2 , Juan Berenguer 3 , Cristina Diez 3 , Juan Carlos López-Bernaldo 3 , Elba L. Herrera 4 , Victor Hontanon 2 , Luis Ibañez-Samaniego 5 , Maria Luisa Montes 2 , Salvador Resino 1 , Amanda Fernández-Rodríguez 1 , María Á. Jimenez-Sousa 1 1 Institute of Health Carlos III, Madrid, Spain, 2 La Paz University Hospital, Madrid, Spain, 3 Hospital General Universitario Gregorio Marañón, Madrid, Spain, 4 Puerta de Hierro Research Institute and University Hospital, Madrid, Spain, 5 University Hospital Gregorio Marañon, Madrid, Spain Background: Human immunodeficiency virus (HIV) infection and cirrhosis are associated with a senescent phenotype that decreases telomere length. We evaluated the impact of hepatitis C virus (HCV) elimination on telomere length in patients with advanced HCV-related cirrhosis after sustained virological monoinfected patients with advanced HCV-cirrhosis (liver decompensation or liver stiffness measurement [LSM] >= 5 kPa or hepatic liver pressure gradient [HVPG] >= 10 mmHg or Child-Pugh-Turcotte (CPT) >= 7). The relative telomere length (RTL) was quantified by real-time multiplex PCR (MMqPCR) on peripheral blood mononuclear cells at baseline and 48 weeks after completing successful DAA therapy. Generalized linear models (GLMs) adjusted for the most relevant clinical and epidemiological variables and mixed GLMs were used. Results: In comparison with HCV-monoinfected patients, HIV/HCV-coinfected patients were younger (p<0.001), had lower BMI (p=0.002), and had been exposed more frequently to interferon (p=0.011). Besides, they were more frequently men (p=0.011), smokers (p=0.005), prior IDUs (p<0.001), and alcohol abusers (p=0.005). RTL was significantly lower in HIV/HCV-coinfected patients than in HCV-monoinfected patients both at baseline (p<0.001), and at the end of follow-up (p=0.032). A significant RTL increase over time was found only for HIV/HCV-coinfected patients (p<0.001), especially in those patients with compensated cirrhosis (p<0.001) (Figure). Conclusion: Eradication of HCV with DAAs was associated with a statistically significant increase in telomere length in HIV/HCV-coinfected patients with advanced cirrhosis, particularly in compensated patients. This finding suggests that HCV clearance may have implications in age-related conditions in this population group. response (SVR) with all-oral direct-acting antiviral agents (DAAs). Methods: Prospective study of 60 HIV/HCV-coinfected and 30 HCV-

586 T-CELL AND MONOCYTE ACTIVATION CORRELATE AND DECLINE DURING HCV THERAPY FOR HCV/HIV Ann W. Auma 1 , Sofi N. Damjanovska 1 , Corinne N. Kowal 1 , Carey Shive 1 , Laura M. Smeaton 2 , Daniel E. Cohen 3 , Debika Bhattacharya 4 , Beverly Alston-Smith 5 , Ashwin Balagopal 6 , Mark Sulkowski 6 , David L.Wyles 7 , Donald D. Anthony 1 1 Case Western Reserve University, Cleveland, OH, USA, 2 Harvard University, Cambridge, MA, USA, 3 AbbVie, Inc, North Chicago, IL, USA, 4 Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center, Torrance, CA, USA, 5 NIH, Rockville, MD, USA, 6 Johns Hopkins University, Baltimore, MD, USA, 7 University of Colorado Denver, Denver, CO, USA Background: Immune activation predicts morbidity in HCV, HIV and HCV-HIV co-infection despite antiretroviral therapy (ART). HCV DAA therapy is associated with partial/complete normalization of soluble markers of immune activation during HCV infection. How this extends to cellular immunity during HCV-HIV infection is less clear. Methods: We analyzed plasma and PBMC from AIDS Clinical Trials Group (ACTG) A5329, where ART treated HCV-HIV co-infected participants were treated with paritaprevir/ritonavir/ombitasvir+dasabuvir+/-ribavirin for 24 (n=36) or 12 (n=9) weeks. In a subset of participants where viable samples were available (n=21 24 week therapy and n=7 12 week therapy) we performed flow cytometric analysis of T-cells, central memory (CM)/effector memory (EM) subsets, monocyte subsets (CD14+CD16- classical, CD14+CD16+ inflammatory, and CD14-CD16+ patrolling), and cell activation (CD38 and HLA-DR expression) before (w0), during (w12) and after therapy (w36) to assess changes (Wilcoxon Signed Rank Test) pooled over the entire sample. Spearman’s correlations evaluated associations between soluble immune activation markers (plasma sCD14, sCD163, IP10 and IL6) and T cell and monocyte subset/activation. Results: CD38/HLA-DR co-expression on CD4 and CD8 memory T-cells decreased 12 weeks after initiation of DAA therapy (p<0.05, Table 1), and for some parameters at w36 (CD8 CM p=0.02, and CD4EM p=<0.001). HLA-DRhi expressing classical monocyte frequency tended to decrease at 12 weeks (p=0.06). Before therapy, HLA-DR expression on classical and inflammatory monocytes positively correlated with absolute counts of CD4 co-expressing CD38/HLA-DR (r=0.56, p=0.001), CD4CM (r=0.46, p=0.009), and CD4EM (r=0.43, p=0.02) T-cells, and CD8 CD38/HLA-DR co-expressing frequencies (CD8 r=0.38, p=0.04, CD8CM r=0.47, p=0.08 and CD8EM r=0.38, p=0.04) T-cells. Before DAA therapy IL-6 levels negatively correlated with classical monocyte frequency (r= -0.45, p=0.01), while 36 weeks after therapy initiation plasma sCD14 positively correlated with CD4s co-expressing CD38/HLA-DR (r=0.67, p=0.004) and CD4+CM (r=0.74, p=0.001) cells. Conclusion: In this sample (n=28), memory T-cell activation associated with monocyte subset activation during HCV-HIV co-infection, consistent with related underlying mechanisms. 12 weeks following therapy initiation, monocyte, CD4 and CD8 activation was reduced. Residual memory CD4 activation after HCV therapy associated with sCD14, potentially attributable to ART controlled HIV immune activation.

Poster Abstracts

CROI 2020 211