Biomarkers of Replication and Injury in HBV/HIV

HBV/HIV 复制和损伤的生物标志物

• 批准号: 10326569
• 负责人: KENNETH E SHERMAN
• 金额: $ 23.67万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-12 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10326569
• 关键词: AIDS clinical trial group; Africa South of the Sahara; Antigens; Biological Assay; Biological Markers; Blood; Blood Tests; CD4 Lymphocyte Count; Categories; Chronic; Cirrhosis; Clinical; Cross-Sectional Studies; Data; Detection; Development; Diagnostic; Disease; Enrollment; Europe; Evolution; Frequencies; Future; Gene Silencing; Genetic Transcription; Ghana; Goals; HIV; HIV Infections; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B Therapy; Hepatitis B Virus; Hepatitis C Therapy; Individual; Injury; Intervention; Laboratories; Lead; Liver; Liver diseases; Monitor; Morbidity - disease rate; National Institute of Allergy and Infectious Disease; Natural History; Nucleosides; Persons; Prognosis; Randomized; Research; Risk; Role; Sampling; Serology; Serum; Staging; Strategic Planning; Surface Antigens; Tenofovir; Testing; Tissues; Transcript; Treatment outcome; United States National Institutes of Health; Universities; Validation; Viral; Viral Load result; Virus Diseases; Virus Replication; acute infection; adefovir; base; biomarker identification; chronic infection; clinical care; co-infection; cohort; exosome; global health; innovation; interest; liver injury; mortality; novel; novel marker; nucleoside analog; pgRNA; repository; response; response biomarker; treatment response; trial comparing; two-arm trial; viral DNA; virus core

Abstract Hepatitis B virus (HBV) is a serious global health concern. In those with HIV it is associated with increased risk of chronicity after acute infection, and increased rates of liver-associated mortality. The field of HBV treatment is undergoing evolution, changing focus from HBV DNA suppression to functional and complete HBV cure. Biomarkers that provide clear guidance regarding prediction, treatment outcome and accurate information regarding liver injury are limited. Though research use of newer HBV biomarkers including pgRNA, quantitative surface antigen and HBV core-related antigen has accelerated in the last year, very limited data exists with regard to their use and utility among persons living with HIV (PLWH). In this Exploratory R21 application we propose to evaluate the potential role of several biomarkers that have not been previously characterized in those with HBV/HIV coinfection. HBV pgRNA represents a transcript of the cccDNA minichromosome that is central to development and perpetuation of HBV chronicity. Using 3 complementary cohorts of PLWH, we will evaluate the association of these biomarkers with CD4 count, HIV viral load and other demographic and serologic HBV markers stratified by categorical natural history replicative stages of HBV disease. In one AIDS Clinical Trials Group (ACTG) cohort, we will examine longitudinal changes in these biomarkers associated with initiation of nucleoside therapy. Our laboratory has recently implemented use of a new blood-based cccDNA assay which will be utilized in conjunction with the pgRNA assays to determine the frequency and proportion of gene silencing. Using novel liver-derived exosome markers of liver injury we will explore whether gene silencing is associated with lower levels of liver injury than are identified with more traditional markers of response such as serum ALT. This characterization will provide key information that may inform future cure strategies for HBV, in PLWH which are being studied within the ACTG and elsewhere.

摘要