CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

553 HEPATIC FIBROSIS DETERMINED WITH MRE SIGNIFICANTLY PREDICTS COGNITIVE IMPAIRMENT Marianna K. Baum 1 , Javier Tamargo 1 , Richard L. Ehman 2 , Chrisina S. Meade 3 , Kenneth E. Sherman 4 , Heidi L. Meeds 4 , Jun Chen 2 , Sabrina S. Martinez 1 , Gustavo G. Zarini 1 , Yongjun Huang 1 , Colby Teeman 1 , Jacqueline Hernandez 1 , Angelique Johnson 1 , Raul Mandler 5 , Adriana Campa1, for the MASH Team 1 Florida International University, Miami, FL, USA, 2 Mayo Clinic, Rochester, MN, USA, 3 Duke University, Durham, NC, USA, 4 University of Cincinnati, Cincinnati, OH, USA, 5 National Institute on Drug Abuse, Rockville, MD, USA Background: Liver disease is a leading cause of morbidity and mortality among people living with HIV (PLWH), and has been associated with neurocognitive impairments (NCI) in PLWH, even in the absence of viral hepatitis. Yet, co- infection with HCV is associated with greater NCI irrespective of cirrhosis or substance abuse. Associations have been reported between indirect measures of liver fibrosis and NCI in PLWH. However, studies using more sensitive markers of liver fibrosis are needed. Magnetic resonance elastography (MRE) is currently the most accurate non-invasive measure of liver fibrosis. Methods: Cross-sectional analysis of 211 HIV mono-infected (HIV+), 74 HCV mono-infected (HCV+), 76 HIV/HCV coinfected and 265 HIV/HCV uninfected individuals from the Miami Adult Studies on HIV (MASH) Cohort. NCI was determined with the Mini Mental State Examination (MMSE). Neurofilament light chain (NFL), a biomarker of neurodegeneration, was tested in plasma of 26 individuals. Substance use was assessed by questionnaire and urine drug screen. Liver fibrosis indicative of liver disease was determined as liver stiffness (LS) via MRE. Results: LS was negatively correlated with MMSE scores (rho=-0.11, p=0.008) and directly correlated with NFL (rho=0.46, p=0.017). LS >2.9 kPa (fibrosis) was more prevalent in HCV+ not virally suppressed than those virally suppressed (56.9% vs 29.2%, p=0.002). HCV infection was associated with 3.42 (1.97-5.94) and 1.72 (0.99-2.99) the odds for inflamed or fibrotic liver (LS >2.5 kPa) compared to HIV+ and uninfected participants, respectively (p<0.0001). HIV infection was associated with decreased odds for LS >2.5 kPa (adjusted OR 0.71 [0.46-1.08], p=0.007) compared to HIV/HCV uninfected individuals. In PLWH, use of prescription opioids increased the odds for inflamed or fibrotic liver (adjusted OR: 1.62 [0.80-3.24], p=0.008) compared to opioid non-users. Hepatic fibrosis was associated with an adjusted odds ratio of 2.43 (1.28-4.59, p=0.006) for NCI (MMSE ≤24) compared to no fibrosis. In PLWH, cocaine use increased the odds for NCI compared to non-use (adjusted OR: 1.32 [0.67-2.61], p=0.036). Conclusion: Hepatic fibrosis is associated with NCI irrespective of HIV and/ or HCV infection. Substance abuse may contribute to liver disease and cognitive impairments in PLWH. Longitudinal studies with comprehensive neuropsychological testing are needed. 554 CHANGES IN LIVER CANCER SURVIVAL IN HIV INFECTION AFTER MANAGEMENT OPTIMIZATION Miguel Rodríguez-Fernández 1 , Nicolás Merchante 1 , Francisco Rodríguez- Arrondo 2 , Boris Revollo 3 , Sofía Ibarra 4 , Esperanza Merino 5 , Maria J. Galindo 6 , Marta Montero 7 , Francisco Téllez 8 , Antonio Rivero-Juárez 9 , Miguel García- Deltoro 10 , Ignacio D. Santos Gil 11 , Marcial Delgado-Fernández 12 , Juan A. Pineda 1 , for the Grupo para el Estudio de las Hepatitis Víricas (GEHEP-002) 1 Hospital Universitario de Valme, Seville, Spain, 2 Hospital Donostia, San Sebastián, Spain, 3 Hospital Germans Trias i Pujol, Barcelona, Spain, 4 Hospital de Basurto, Basurto, Spain, 5 Hospital General Universitario de Alicante, Alicante, Spain, 6 Hospital Clinic of Valencia, Valencia, Spain, 7 Hospital Universitario y Politecnico La Fe, Valencia, Spain, 8 Hospital Universitario de Puerto Real, Cadiz, Spain, 9 Hospital Universitario Reina Sofia, Cordoba, Spain, 10 Hospital General de Valencia, Valencia, Spain, 11 Hospital Universitario de La Princesa, Madrid, Spain, 12 Hospital Regional Carlos Haya, Malaga, Spain Background: Hepatocellular carcinoma (HCC) has been an important cause of morbidity and mortality in HIV-infected patients during the last twenty years. Previous studies have shown that the survival after HCC diagnosis in HIV- infected patients is extremely low, mainly as a consequence of late diagnosis and a low rate of treatment. This scenario may be changing in recent years, partly due to the systematic HCC surveillance program implementation in this population. Because of this, we assessed changes in the HCC management and its impact on survival of HIV-infected patients. Methods: Multicenter cohort study (1999-2019). HCC cases diagnosed in HIV- infected patients from the GEHEP-002 cohort were included. The cohort was divided into 2 time periods, according to the year of HCC diagnosis (1999-2009 vs

determined by calculation of the positive predictive value (PPV), sensitivity, specificity and area under the receiving operator curve (AUROC). Results: Incident HCC was diagnosed in 302 HIV+ patients (median age, 56 [IQR, 51-61] years; 299 [99%] male). After chart review, 203 (67.2%, [95% CI, 61.6-72.5%]) had evidence of cirrhosis. Cirrhosis was most commonly identified by radiology (63%) and pathology (32%). Median FIB-4 was 4.37 (IQR, 2.42-7.71) for those with cirrhosis and 2.87 (IQR, 1.66-4.83) for those without cirrhosis (p<0.001). FIB-4 identified patients with cirrhosis with an AUROC of 0.67 (95% CI, 0.60-0.73). FIB-4 >4.0 had a PPV of 78.9% to confirm the presence of cirrhosis with a sensitivity of 55.2% and specificity of 69.7% (Table 1). Conclusion: The diagnostic accuracy of FIB-4 for cirrhosis in the setting of HIV and HCC is modest and may result in misclassification of cirrhosis in this population.

552 PLASMA MIR-99A AND MIR-100 PREDICT LIVER FIBROSIS PROGRESSION IN HIV/HCV SUBJECTS Miguel Angel Martinez 1 , Sandra Franco 1 , Daniela Buccione 2 , Beatriz Mothe 1 , Patricia Cobarsi 2 , Lidia Ruiz 1 , Maria Nevot 1 , Ana Jordan-Paiz 1 , Raquel Pluvinet 2 , Lauro Sumoy 2 , Cristina Tural 2 1 IrsiCaixa Institute for AIDS Research, Badalona, Spain, 2 Hospital Germans Trias i Pujol, Barcelona, Spain Background: The lack of available biomarkers to diagnose and predict different stages of liver disease, such as NAFLD and NASH, with a non-invasive strategy is currently one of the main challenges that clinicians are facing. Recent evidence indicates that the plasma levels of specific microRNAs (miRs) may be significantly altered in subjects with liver injury, including HIV infected individuals. Methods: Large-scale deep sequencing analysis of small RNA expression was performed on plasma samples from 46 HIV-1/HCV co-infected subjects that did not exhibit liver fibrosis at the time of sampling. After a mean of 10.3 years, 26 of the former subjects developed liver fibrosis (F2-4) and 20 remained without signs of liver fibrosis (F0-1). Twenty one healthy uninfected donors were also analyzed. Results: At the time of sampling, there were not significant clinical differences between liver fibrosis progressing and non-progressing subjects (i.e. sex, age, AST, ALT, GGT, platelets, FIB-4, liver fibrosis). A total of 1355 different miRs were identified. When compared with healthy donors, HIV-1/HCV subjects showed significant (fold change> 2 and adjusted p< 0.05) dysregulated expression of 44 miRs, 38 of them upregulated (ranging from 13.8 to 2.0 fold increase). Previously described circulating miRs associated with NAFLD in the general population, miR-122, miR-34a and miR-192, were also found here within the 38 upregulated miRs. Of the 38 upregulated miRs, 7 (miR-885-5p, miR-100-5p, miR-193-5p, miR-99a-5p, miR-203a-3p, miR-5588-5p and miR-99a-3p) were significantly upregulated in the 26 subjects that progressed to liver fibrosis when compared to the 20 subjects that did not progressed (p< 0.005). Two of these miRs, miR-99a-5p and miR-100-5p, were highly associated with liver fibrosis progression (p< 0.0001) and displayed a significant linear correlation with liver fibrosis values of the entire study cohort (r= 0.51, p= 0.0003 and r= 0.48, p= 0.0006, respectively). Conclusion: Circulating miR-99a-5p and miR-100-5p are significantly associated with liver fibrosis progression in subjects with HIV-1/HCV co- infections, even before liver fibrosis is detectable. This study demonstrates the potential of miRs as biomarkers in the progression of liver injury in HIV-infected subjects. Levels of miR-99a-5p and miR-100-5p may be suitable markers of liver fibrosis amelioration in HIV-1/HCV co-infected patients treated with HCV DAAs and cured of HCV infection.

Poster Abstracts

CROI 2020 198