CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

restoration of NK and CD8, however, little is known on the effects of DAAs on gd, Th17 and Treg which all play a role in liver fibrogenesis. Further, while B-cell activation has been linked to extrahepatic manifestations of HCV, literature is lacking on the role of these cells in liver damage. Methods: We enrolled 97 virally-infected (VI) subjects (15 HIV cART- suppressed; 35 HCV naive to HCV therapy; 47 HIV/HCV cART-suppressed and naive to HCV therapy) and 10 age-matched healthy controls (HC). All HCV-infected individuals underwent DAA therapy. At baseline (T0) and 12 weeks after End of Treatment (SVR12) we measured: (i) γδ frequency (CD3+Pan γδ+), activation (CD69/CD38), (ii) Th17-like (CD4+CD161+CCR6+); (iii) Treg (CD4+CD25+CD127-); (iv) B cell frequency (CD19+), activation (CD86/CD38); v) γ-globulin levels.vi) Fibrosis stage was determined by transient elastography (Fibroscan) Statistical analysis as appropriate Results: At T0, VI presented lower Th17 and higher Treg versus HC (Fig1A). DAA led to a further contraction of Th17 and no changes in Treg frequency (Fig.1B). While total γδ were comparable in VI and HC both prior to and following treatment (Fig.1B), activated γδ subset decreased upon DAA (Fig.1C). Compared to HC, VI also featured higher B-cell frequencies and activation which both decreased during DAA (Fig1C). Accordingly, γ-globulin concentrations also diminished in HCV mono and co-infection following DAA and correlated with B-cell activation (Fig1D). In VI, a low vδ2/Th17 ratio, known to predict liver damage, increased from baseline to SVR12, yet remained lower than HC (HIV/ HCV vs HC: p=.04; HCV vs HC: p=.03) and negatively correlated with liver stiffness (Fig.1E) and serum ALT and AST (Fig.1F) Further, also γ-globulin levels were positively linked to liver fibrosis indexes following DAAs (r=0.6, p<.0001). No differences in B and T cell phenotypes were registered (Fig1A). Conclusion: Effective DAA in both HCV- mono and HIV/HCV co-infected subjects resulted in decreased B- and γδ cell activation, with recovery of vδ2/ Th17 ratio. These changes are linked to the reduction of hepatic necrosis and stiffness, suggesting that DAA-mediated lightening of the pro-inflammatory liver insult may limit organ damage.

587 IMPACT OF HCV CLEARANCE ON NK CELLS AND HIV TRANSCRIPTION IN COINFECTED SUBJECTS Maria L. Polo 1 , Alejandra Urioste 1 , Yanina Ghiglione 2 , Jimena Salido 2 , Ajantha Solomon 3 , Maria J. Rolon 4 , Horacio Salomón 2 , Florencia Quiroga 1 , Gabriela Turk 2 , Sharon R. Lewin 3 , Natalia Laufer 1 1 National Scientific and Technical Research Council, Buenos Aires, Argentina, 2 Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, UBA-CONICET, Ciudad Autónoma de Buenos Aires, Argentina, 3 Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia, 4 Hospital Dr. Juan A. Fernández, Buenos Aires, Argentina Background: Hepatitis C is a frequent coinfection in people living with HIV. HCV replication and its subsequent clearance with direct acting antivirals (DAA) can potentially modify how HIV persists on antiretroviral therapy (ART). Natural killer (NK) cells are key effectors against both viruses and may be involved in shaping HIV reservoir. In this regard, we studied NK cell phenotype before and after HCV treatment with DAAs and its association with the dynamics of HIV reservoir. Methods: In a prospective longitudinal observational study, HIV/HCV- coinfected individuals on suppressive cART (n=19) received sofosbuvir/ daclatasvir alone or with ribavirin (n=7). Blood samples were obtained before HCV treatment (baseline sample, BSL), at end-of-treatment (EOT) and at 12 months after EOT (12MPT). Cell-associated (CA) HIV DNA (total, integrated, 2LTR), unspliced (US) and multiply-spliced (MS) RNA were quantified by real- time PCR. Expression of HLA-DR, CD38, NKG2D, NKp46, NKp30, CD95, CD69, CD25 on NK cells was evaluated by flow cytometry. Data was analyzed using non-parametric statistics. Results: At 12MPT, US-RNA and US/MS ratio were significantly higher than at BSL (p=0.02 and p=0.03, respectively). No changes in CA-DNA were observed. At EOT, surface expression of HLA-DR, CD38, HLADR/CD38, NKG2D, and CD95, decreased compared to BSL (p=0.0002, p=0.006, p=0.0005, p=0.001 and p=0.001, respectively). CD95+, HLA-DR+, and HLA-DR+/CD38+ NK cells rebounded at 12MPT compared to EOT. Higher percentages of non-activated NK cells were observed at EOT (HLA-DR-/CD38- and CD25-/CD69-/CD95-) and at 12MPT (HLA-DR-/CD38-). Overall, higher levels of EOT and 12MPT NK cell activation correlated with higher 12MPT US-RNA. Particularly, EOT-expression of HLA-DR correlated with 12MPT US-RNA (r=0.57, p=0.04). Also, 12MPT CD38 expression correlated with fold change in US-RNA levels between12MPT and BSL (r=0.5919, p=0.0462). Conclusion: Downregulation of NK cell activation was observed immediately after HCV clearance although some markers rebounded one year later, in concomitance with increased transcriptional activity of HIV reservoir. This may be reflecting the priming of NK cells by the residual HIV transcription and might point out a role for NK cells in shaping HIV persistence. 588 CHANGES IN IMMUNE-CELL SUBSETS IN HCV AND HCV/HIV PATIENTS UPON VIRALLY EFFECTIVE DAA Elvira S. Cannizzo 1 , Camilla Tincati 1 , Esther Merlini 1 , Anna De Bona 2 , Lorena Van Den Bogaart 3 , Roberta Curetti 2 , Spinello Antinori 3 , Antonella D'Arminio Monforte 1 , Giulia Marchetti 1 , Laura Milazzo 3 1 University of Milan, Milan, Italy, 2 Azienda Ospedaliera San Paolo, Milan, Italy, 3 Fatebenefratelli Sacco Hospital, Milan, Italy Background: Direct-Acting Antivirals (DAAs) eradicate HCV and reduce liver fibrosis by containing inflammation. Virologic response correlates with the

Poster Abstracts

589 LIVER FIBROSIS HINDERS NORMALIZATION OF SYSTEMIC INFLAMMATION AFTER HCV ERADICATION

Clara Restrepo 1 , Beatriz Álvarez 2 , Marcial García 1 , María Ángeles Navarrete 1 , Maria Ángeles Jiménez-Sousa 3 , Laura Prieto 2 , Alfonso Cabello 2 , Sara Nistal 4 , Salvador Resino 3 , Miguel Górgolas Hernández-Mora 2 , Norma Rallón 1 , José M. Benito 1 1 Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid, Spain, 2 Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain, 3 Institute of Health Carlos III, Madrid, Spain, 4 Hospital Universitario Rey Juan Carlos, Madrid, Spain Background: HCV co-infection significantly impacts on inflammation, endothelial activation and coagulation function parameters leading to several comorbidities among people living with HIV (PLWH). The new direct-acting antivirals (DAAs) therapy achieves eradication of HCV in the majority of patients. However, the early effect of HCV eradication on these parameters on PLWH has been scarcely explored. We have analyzed the effect of HCV on systemic inflammation and endothelial/coagulation function in PLWH and its evolution after HCV eradication with DAAs.

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