CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

the independent predictors of mortality were BCLC stage at presentation, alfa- fetoprotein levels and lack of previous ultrasound surveillance. HIV infection did not show any trend for an independent association (HR 1.07; 95% CI: 0.74-1.54; p=0.7). Conclusion: HIV coinfection has no impact on the survival after the diagnosis of HCC in HCV-infected patients. Although the mortality of HCC is somewhat higher in HIV/HCV-coinfected patients, these differences seem to be related with a later diagnosis of HCC in HIV-infected patients and not with HIV infection itself or a lower access to HCC therapy. Miguel Rodríguez Fernández 1 , Nicolás Merchante 1 , Maria J. Rios-Villegas 2 , Koldo Aguirrebengoa 3 , Maria A. García-Gonzalo 4 , Joseba Portu 5 , Francisco Vera 6 , Marina Villalobos 7 , Carlos Mínguez 8 , Miguel Angel Lopez Ruz 9 , Mohamed Omar 10 , Carlos Galera 11 , Blanca Figueruela López 1 , Juan A. Pineda 1 , for the Grupo para el Estudio de las Hepatitis Víricas (GEHEP) 1 Hospital Universitario de Valme, Seville, Spain, 2 Hospital Universitario Virgen Macarena, Sevilla, Spain, 3 Hospital de Txagorritxu, Vitoria, Spain, 4 Hospital de Galdakao, Galdakao, Spain, 5 Hospital Universitario de Cruces, Barkaldo, Spain, 6 Hospital General Universitario Santa Lucía, Cartagena, Spain, 7 Hospital Virgen de la Victoria, Málaga, Spain, 8 Hospital La Magdalena, Castellón, Spain, 9 University Hospital Virgen de las Nieves, Granada, Spain, 10 Complejo Hospitalario de Jaén, Jaén, Spain, 11 Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain Background: Surveillance of hepatocellular carcinoma (HCC) by hepatic ultrasound (US) every 6 months is recommended in HIV-infected patients with cirrhosis. However, there are no specific studies addressing the performance of such strategy in this population. As it has been reported that HCC could have a more aggressive course in the HIV-infected patient, the effectiveness of this surveillance policy needs to be specifically evaluated in the scenario of HIV infection. Objective: To assess the performance of US surveillance for the diagnosis of HCC in HIV-infected patients. Methods: The GEHEP-002 cohort recruits HCC cases diagnosed in HIV-infected patients from 32 centers across Spain. The proportion of ‘US lack of detection’, defined as HCC diagnosed within the first 3 months after a normal surveillance US, and the proportion of ‘surveillance failure’, defined as cases in which surveillance failed to detect HCC at early stage (BCLC stage 0-A), were assessed. To assess the impact of HIV, a control population of 104 HCC cases diagnosed in HCV-monoinfected patients during the study period was used. Results: 186 (54%) out of 346 HCC cases in HIV+ patients and 62 (60%) out of 104 cases from the control group were diagnosed within a US surveillance program. US lack of detection occurred in 16 (8.6%) of 186 HIV+ patients diagnosed by surveillance whereas this occurred in 5 (8.6%) in the control group (p=1.0). HCC cases after US lack of detection in HIV+ patients were more frequently at Child-Pugh stage C and had an advanced stage at diagnosis. The performance of US surveillance to achieve an early diagnosis of HCC was significantly lower for HIV+ patients. Thus, US surveillance failure occurred in 107 (57%) out of 186 cases diagnosed by screening in HIV+ patients whereas this occurred in 18 (29%) in the control group (p<0.0001). Similarly, US surveillance failed to detect HCC within Milan criteria in 104 (56%) out of 186 cases diagnosed by screening in HIV+ patients whereas this occurred in 18 (29%) in the control group (p< 0.0001). The probability of 1-year and 2-year survival after HCC diagnosis among those diagnosed by screening was 56% and 45% in HIV+ patients whereas it was 79% and 64% in HIV-negative patients (p=0.038). Conclusion: The performance of US surveillance of HCC in HIV-infected patients is very poor and worse than that shown outside HIV infection. A HCC surveillance policy based on US examinations every 6 months might be insufficient in HIV- infected patients with cirrhosis. 610 INTRAHEPATIC HIV IS ASSOCIATED WITH ADVERSE LIVER OUTCOMES IN HIV-HBV COINFECTION Jennifer M. Zerbato 1 , Kasha P. Singh 1 , Ajantha Solomon 1 , Ashanti Dantanarayana 1 , Surekha Tennakoon 1 , Megan Crane 2 , David Price 3 , Sabine Braat 3 , Hugh Mason 1 , Peter Revill 1 , Jennifer Audsley 1 , Anchalee Avihingsanon 4 , Sharon R. Lewin 1 609 LOW PERFORMANCE OF ULTRASOUND SURVEILLANCE FOR THE DIAGNOSIS OF LIVER CANCER IN HIV

1 Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia, 2 Peter MacCallum Cancer Centre, Melbourne, VIC, Australia, 3 University of Melbourne, Melbourne, VIC, Australia, 4 Chulalongkorn University, Bangkok, Thailand Background: Individuals who are coinfected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) have a 17 times increased risk of liver- related mortality than HBV mono-infected individuals. Given HIV can infect multiple cells in the liver including hepatocytes, Kupffer cells, stellate cells and intrahepatic T-cells, we hypothesized that the frequency of HIV-infected cells in the liver would be associated with HBV disease or liver-related clinical outcomes in a cohort of HIV-HBV coinfected individuals in Bangkok, Thailand. Methods: Peripheral blood and matched liver biopsies were collected from 39 HIV and HBV coinfected participants prior to initiating antiretroviral therapy (ART). We measured cell-associated unspliced (US) HIV RNA and HIV DNA in CD4+ T-cells from blood and total liver biopsies and HBV covalently closed circular DNA (cccDNA) in liver biopsies by qPCR. Liver inflammation/damage was measured by transient elastography (TE). Lipopolysaccharide (LPS), CXCL10, and soluble CD14 (sCD14) were measured in plasma by ELISA and mRNA for CXCL10 and CXCR3 measured in liver biopsies by RT-qPCR. Results: Participants were 90%male with a median age of 31.9 years and a median CD4 nadir of 320 (range 20-1197). All individuals were HBsAg+ and 64% were HBeAg+. HIV DNA and RNA were detected in liver biopsies in 63.2% and 44.7% of participants, respectively. There was a significant association between HIV DNA and RNA in liver (p<0.0001) and between liver and plasma HIV RNA (p=0.0320). There was no relationship between intrahepatic HIV and CD4 count. Intrahepatic HIV DNA was significantly associated with markers of liver disease, including AST (p=0.0250) and TE (p=0.0164), intrahepatic T-cell inflammatory markers CXCL10 (p=0.0165) and CXCR3 (p=0.0025), as well as sCD14 in plasma (p=0.0051). Intrahepatic HIV RNA was also significantly associated with CXCL10 (p=0.0061). There was a trend towards higher levels of cccDNA in individuals who had detectable intrahepatic HIV DNA. HIV DNA and RNA in circulating CD4+ T-cells were not associated with any liver or HBV related outcomes. Conclusion: Prior to ART, HIV DNA and RNA are frequently detected in the liver and are associated with multiple clinical markers of liver disease in HIV-HBV coinfection. The cellular localisation of HIV DNA and RNA in the liver requires further investigation but we propose that this is not explained by trafficking T-cells given the absence of any associations between liver disease and HIV DNA and RNA in blood. 611 COMPARTMENTALIZATION OF NS3 AND NS5A RASS IN HIV/HCV GT 1A OR 4D INFECTED PATIENTS Riccardo Vercesi 1 , Giulia Morsica 1 , Hamid Hasson 1 , Emanuela Messina 1 , Caterina Uberti-Foppa 2 , Sabrina Bagaglio 1 1 Ospedale San Raffaele, Milano, Italy, 2 San Raffaele Vita-Salute University, Milan, Italy Background: Naturally occurring resistance-associated substitutions (RASs) in the NS3 and NS5a DAAs target regions are poorly investigated in the liver, the major site of HCV replication. We evaluated the RAS profile of NS3 and NS5a in liver and plasma of HIV/HCV coinfected patients (pts). Methods: Twenty-one HIV/HCV coinfected pts naïve to anti-HCV treatment who performed liver biopsy for diagnostic purposes were included in the study. Fourteen pts harbored HCV genotype (GT)1a and 7 pts harbored GT4d. Median age was 41 years (inter quartile-range, IQR 38-43); 14 were males and 7 females; median alanine amino transferase (ALT) and aspartate amino transferase (AST) values were 66 IU/L (IQR 41-200, normal values < 59 IU/L), 65 IU/L, (IQR 49-137, normal values < 35 IU/L), respectively. CD4 cells count was 486 (IQR 443-614) HCV-RNA load was 5.6 Log IU/mL (IQR 5.5-6). The study was conducted in accordance with ethical principles stated in the Declaration of Helsinki and the patients gave written informed consent. NS3 and NS5a RASs profile was investigated by viral population sequencing in liver tissues and plasma, according to Lontok, 2015, Sarrazin, 2016 and Carrasco, 2018. Results: RASs in the NS3 were detected in 9/21 (43%) coupled liver tissues and plasma samples. NS3 mutated strains in GT1a exhibited Q80K in plasma and liver. In GT4d infected pts, NS3 protease region resulted conserved in plasma and liver. The analysis of the NS5a domain showed RASs in 10/21 (47.6%) liver tissues and 6/21 (28.5%) corresponding plasma samples; in GT1a, 3/14 sequences from liver had RASs [M28R/Q30P/L31R in 1 pt, Q30R/L31R in one other pt, H58E in the remaining pt ] while RASs were not revealed in the corresponding plasma. Interestingly, in GT4d 7/7 (100%) liver tissues and 6/7 plasma samples (85.7%) showed the amino acid substitution T58P at site of resistance.

Poster Abstracts

CROI 2019 231