CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

614 LIVER DISEASE PROGRESSION IN HIV-HBV COINFECTION ON ART IS ASSOCIATED WITH HMGB1 Kasha P. Singh 1 , Jennifer M. Zerbato 2 , Wei Zhao 2 , Sabine Braat 2 , Surekha Tennakoon 2 , Ajantha Solomon 2 , Gail Matthews 3 , Christopher K. Fairley 4 , Joseph Sasadeusz 1 , Megan Crane 5 , Anchalee Avihingsanon 6 , Jennifer Audsley 2 , Sharon R. Lewin 2 1 Doherty Institute for Infection and Immunity, Melbourne, Australia, 2 University of Melbourne, Melbourne, Australia, 3 Kirby Institute, Sydney, NSW, Australia, 4 Monash University, Melbourne, VIC, Australia, 5 Peter MacCallum Cancer Centre, Melbourne, Australia, 6 HIV–NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand Background: In HIV-HBV co-infection, liver disease progression is accelerated, and liver related mortality increased, including in those on antiretroviral therapy (ART). Systemic inflammation and gut permeability are increased in HIV infection and may drive accelerated liver disease. We investigated liver disease progression in HIV-HBV co-infected individuals on ART, and its relationship with inflammatory cytokines and products of microbial translocation. Methods: HIV-HBV co-infected adults on ART were recruited in Australia and Thailand and followed prospectively for 3 years with 6 monthly visits for clinical assessment and blood collection. Liver fibrosis was measured at baseline and yearly using transient elastography (Fibroscan®, Echosens) in kilopascals (kPa). Liver disease progression was defined as (1) an increase in Metavir grade (defined by kPa grade equivalent ranges defined in HIV-HBV infected individuals) or (2) at least 20% or a 2kPa increase in kPa with at least one value > 5.9kPa. Comparisons were made using Wilcoxon rank-sum test for continuous data and chi-square test or Fisher’s exact test for categorical data at baseline and later timepoints. Results: 67 participants (57 male) were enrolled. The mean age was 51 years and median time since HIV diagnosis was 14.8 (interquartile range (IQR) 11.4- 18.7) years. Median nadir CD4+ T cell count was 25 (IQR 35-225) cells/mL. 21/69 were HBeAg+. 11 participants were classified as progressors by fibrosis grade and 7 by kPa. 6 were progressors by both definitions. Progressors had similar baseline characteristics to non-progressors but progressors had significantly higher levels of high mobility group box 1 protein (HGMB1), a marker of cell death, using either definition (definition 1 (p=0.011) and 2 (p=0.041)). Nadir CD4 count was significantly lower in progressors than non-progressors when defined by kPa change (27 and 145 cells/mL respectively; p=0.018). No significant differences were seen between the two groups in other parameters including lipopolysaccharide, soluble CD14 or inflammatory markers including CXCL-10, monocyte chemotactic protein-1 or tumour necrosis factor-a. Conclusion: In the setting of ART, 20% of HIV-HBV co-infected individuals have progressive liver fibrosis. Liver disease progression was associated with higher HMGB1 and lower nadir CD4 count. Interventions to prevent liver disease progression on ART require further investigation. 615 HEPATITIS B VIRUS MUTATIONS ASSOCIATED WITH HEPATOCELLULAR CARCINOMA IN BOTSWANA Sethunya Gotulweng 1 , Motswedi Anderson 1 , Wonderful Choga 1 , Kabo Baruti 1 , Lynnette Bhebhe 1 , Tshepiso Mbangiwa 1 , Bonolo B. Phinius 1 , Sikhulile Moyo 1 , Theresa K. Sebunya 2 , Richard G. Marlink 3 , Max Essex 1 , Rosemary Musonda 1 , Jason T. Blackard 4 , Simani Gaseitsiwe 1 1 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 2 University of Botswana, Gaborone, Botswana, 3 Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA, 4 University of Cincinnati, Cincinnati, OH, USA Background: Hepatitis B virus (HBV) resulted in 887,000 deaths in 2015 due to hepatocellular carcinoma (HCC) and cirrhosis. In sub-Saharan Africa, HCC has been reported in younger individuals, compared to other regions. Mutations within the HBV core, precore, and X regions may lead to rapid progression to HCC. Our aimwas to identify HBV mutations associated with progression to HCC in HIV/HBV co-infected adults in Botswana. Methods: This was a retrospective, cross-sectional study utilizing archived plasma samples from a study conducted at the Botswana Harvard AIDS Institute Partnership (2009-2012). A total of 100 samples from HIV/HBV infected adults were available of which 28 were hepatitis B surface antigen (HBsAg) positive, while 72 were HBsAg negative but HBV DNA positive (occult HBV infections). HBV regions were amplified using a semi-nested polymerase chain reaction. Sequences from Botswana were then compared to GenBank references to identify clinically relevant mutations. Results: Of the 100 samples, 60 could be amplified and sequenced. Thirty six (60%) samples belonged to genotype D, while 24 (40%) were genotype

A. Fifteen samples (25.0%) had 29 mutations which have been previously associated with HCC. Eleven HCC-associated mutations were detected in genotype A, while 18 HCC mutations were detected in genotype D samples. W28* mutation was seen in more than one participant and also occurred as a dual mutation. E64D and L65V were the most common mutations, occuring in 3 participants each. Other common mutations were I127L which also was found in 3 participants followed by K130M and V131I which were seen found in 2 participants. K130M and V131I appeared as a dual mutation. Conclusion: This is the first study to report on the presence of mutations linked to HCC in Botswana. As participants with these mutations might be more prone to rapid disease progression, they may require additional clinical monitoring. Other polymorphisms were also detected but have not been functionally characterized; thus, future in vitro studies on these mutations are warranted.

616 HEPATOCELLULAR CARCINOMA SCREENING AMONG HIV/HBV-COINFECTED INDIVIDUALS IN ZAMBIA Carlotta Riebensahm 1 , Helen Chitundu 2 , Belinda Varaidzo Chihota 3 , Edford Sinkala 2 , Lloyd Mulenga 2 , Veronica Sunkutu 2 , Adrià Ramírez Mena 1 , Matthias Egger 4 , Carolyn Bolton Moore 5 , Michael J. Vinikoor 5 , Gilles Wandeler 1 1 University Hospital of Bern, Bern, Switzerland, 2 University Teaching Hospital, Lusaka, Zambia, 3 Center for Infectious Diseases Research, Lusaka, Zambia, 4 Institute of Social and Preventive Medicine, Bern, Switzerland, 5 Center for Infectious Disease Research in Zambia, Lusaka, Zambia Background: Chronic hepatitis B virus (HBV) infection is the single most important cause of hepatocellular carcinoma (HCC) in sub-Saharan Africa (SSA). Six-monthly abdominal ultrasound (AUS) screening allows the early diagnosis of HCC and reduces related mortality. However, very few HCC screening programs exist in the region to date. We took advantage of a cohort of HIV/HBV-coinfected individuals in Zambia to pilot an AUS-based screening program in primary care clinics. Methods: We enrolled HIV/HBV-coinfected adults on antiretroviral therapy (ART) at two outpatient clinics in Lusaka, Zambia. In line with international recommendations, we performed AUS imaging every 6 months in all participants and collected data using a standardized case-report form. All patients had yearly liver stiffness measurements using transient elastography (TE; Fibroscan 402®), HBV viral load, HBV serology, and alcohol consumption assessments using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C). We summarized the findings of the first AUS examination for the cohort. Results: Of 306 HIV/HBV-coinfected patients included, 59.5%were male and the median age was 34 years (interquartile range 28-39). Their median CD4 count was 234 cells/µL (108-336), 36.8% had WHO clinical stage 3 or 4, and 140 (45.8%) reported hazardous alcohol consumption, defined as AUDIT-C >3 for women and >4 for men. HBV DNA >2000 IU/mL was observed in 54.7% of participants and 43.3%were HBeAg-positive. At ART initiation, significant fibrosis (>7.0kPa; equivalent to Metavir score ≥F2) was seen in 15.4% of patients and cirrhosis (>9.4kPa; F4) in 8.0%. On AUS, 84 (27.5%) participants had hepatomegaly, 71 (23.2%) peri-portal fibrosis, whereas 5 individuals (1.6%) had signs of cirrhosis, including surface nodularity, coarse and heterogeneous echotexture, atrophy or segmental hypertrophy, and 4 (1.3%) had liver steatosis. Of nine patients with a hyperechoic or hypoechoic lesion, 7 (77.8%) were male, 8 (88.9%) showed elevated levels of ALT prior to ART initiation, 2 (22.2%) were HBeAg-positive and 1 had HBV DNA levels >2,000 IU/mL. Four patients with a lesion had significant fibrosis, of whom one had cirrhosis, according to TE. Conclusion: We report results from one of the first HCC screening programs in SSA. At their first assessment, 9 of 306 HIV/HBV-coinfected individuals had a liver lesion, indicating the need for further diagnostic testing. Our data also suggest AUS under-estimates cirrhosis.

Poster Abstracts

CROI 2020 222