HBV HIV Coinfection Research Network

HBV HIV 合并感染研究网络

• 批准号: 8503643
• 负责人: RICHARD K. STERLING
• 金额: $ 52.5万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-23 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8503643
• 关键词: AIDS clinical trial group; Address; Adoption; Affect; Age; Ancillary Study; Benefits and Risks; Biopsy; Chronic; Chronic Hepatitis B; Clinical; Comorbidity; Critiques; DNA; Data; Data Coordinating Center; Development; Disease; Disease Progression; Face; Frequencies; Funding; Goals; Guidelines; HBV Liver Disease; HIV; HIV-1; Health Sciences; Hepatitis B; Hepatitis B Virus; Hepatitis B e Antigens; Hepatitis C virus; Highly Active Antiretroviral Therapy; Histologic; Histology; Impairment; Infection; Investigation; Kidney; Knowledge; Lamivudine; Life; Liver; Liver Cirrhosis; Liver Fibrosis; Liver diseases; Measures; Morbidity - disease rate; Natural History; North America; Outcome; Pathologist; Patients; Persons; Population; Populations at Risk; Positioning Attribute; Primary carcinoma of the liver cells; Published Comment; Regimen; Research; Research Personnel; Resistance; Resources; Risk; Serologic tests; Serological; Serum Markers; Severities; Structure; Tenofovir; Treatment outcome; United States National Institutes of Health; Variant; Viral; Virus; Virus Diseases; antiretroviral therapy; base; bone; chronic liver disease; cohort; elastography; emtricitabine; improved; liver biopsy; meetings; mortality; novel; patient population; public health relevance

DESCRIPTION (provided by applicant): Since the introduction of highly active antiretroviral therapy (ART) in 1996, there has been a dramatic reduction in morbidity and mortality among those living with HIV. However, chronic liver disease due to coinfection with hepatitis B (HBV) or C (HCV) virus has emerged as the second leading cause of mortality among HIV-infected persons. The natural history of HBV infection is altered in those with HIV. Current guidelines recommend that most coinfected patients be treated for both HIV and HBV infection using combinations of ART that include tenofovir (TDF). Despite widespread adoption in the US, the effect of this regimen on long-term outcomes of HBV disease such as histologic severity, progression, and risk of emergence of resistant HBV variants, and the long term risks of TDF therapy remains unanswered. Further investigation is required to address the following important questions: (1) what is the proportion of HIV-coinfected patients who have incomplete viral suppression on TDF? (2) is incomplete suppression of HBV acceptable in HIV coinfected persons and if so, what threshold HBV DNA level constitutes an adequate clinical goal? (3) in view of the lack of acceptance of liver biopsy among HIV practitioners, can noninvasive markers accurately assess HBV disease activity and the impact of ART on disease progression? (4) What are the long term risks of TDF-based therapy for HBV in HIV coinfection? In short, what are the risks and benefits of TDF-based therapy for CHB in patients with HIV coinfection? The NIH Hepatitis B Research Network (HBRN) is the first major effort to elucidate the natural history and treatment outcomes of persons with chronic HBV the US. The HBRN will not address the critical issue of HBV liver disease progression in HIV-infected persons because patients with HIV coinfection will be excluded. The current proposal, an approved ancillary study of the HBRN, offers a unique opportunity to fill major gaps in HBV-HIV knowledge and to compare HBV-HIV infected persons to those with HBV monoinfection participating in the HBRN. No other funded research network in North America has the expertise, patient population, and structure to carry out the proposed studies. The Specific Aims are: 1. Define the problem. We will clinically, histologically, serologically, and virologically characterize a well-defined cohort of HBV-HIV patients in North America in a cross-sectional manner; 2. Define the benefit of long term therapy. We will longitudinally determine the impact of complete vs. incomplete viral suppression on clinical and serologic outcomes, and histologic progression by paired biopsy and 2a. Define a threshold HBV DNA level associated with disease progression; 2b. Establish the utility of noninvasive assessment of hepatic fibrosis compared with biopsy; and 2c. Define the frequency of genotypic and phenotypic TDF resistance with long term therapy; and finally 3. Define the risk of long term therapy. We will assess the long term renal and bone effects of TDF-based therapy in the HBV-HIV cohort. Collectively, this study will fulfill many of the key priorities outlined in the NIH Action Plan fo Liver Disease for HBV-HIV coinfection.

描述（由申请人提供）：自 1996 年引入高效抗逆转录病毒疗法 (ART) 以来，艾滋病毒感染者的发病率和死亡率急剧下降。然而，由乙型肝炎（HBV）或丙型肝炎（HCV）病毒合并感染引起的慢性肝病已成为艾滋病毒感染者死亡的第二大原因。 HIV 感染者的 HBV 感染自然史发生了改变。目前的指南建议大多数合并感染的患者使用包括替诺福韦 (TDF) 在内的 ART 组合来治疗 HIV 和 HBV 感染。尽管该方案在美国得到广泛采用，但该方案对 HBV 疾病长期结果（如组织学严重程度、进展和耐药 HBV 变异出现的风险）以及 TDF 治疗的长期风险的影响仍未得到解答。需要进一步调查来解决以下重要问题：（1）TDF 病毒抑制不完全的 HIV 合并感染患者的比例是多少？ (2) 对于 HIV 合并感染者来说，不完全抑制 HBV 是否可接受？如果可以，什么阈值 HBV DNA 水平构成足够的临床目标？ （3）鉴于HIV从业者对肝活检的接受度不够，无创标记物能否准确评估HBV疾病活动性以及ART对疾病进展的影响？ (4) HIV 合并感染中基于 TDF 的 HBV 治疗的长期风险是什么？ 简而言之，对于 HIV 合并感染患者，基于 TDF 的 CHB 治疗有何风险和益处？ NIH 乙型肝炎研究网络 (HBRN) 是第一个旨在阐明美国慢性乙型肝炎患者的自然史和治疗结果的重大努力。 HBRN 不会解决 HIV 感染者中 HBV 肝病进展的关键问题，因为 HIV 合并感染的患者将被排除在外。目前的提案是一项经批准的 HBRN 辅助研究，提供了一个独特的机会来填补 HBV-HIV 知识的主要空白，并将 HBV-HIV 感染者与参与 HBRN 的 HBV 单一感染者进行比较。北美没有其他资助的研究网络拥有开展拟议研究的专业知识、患者群体和结构。具体目标是： 1. 定义问​​题。我们将从临床、组织学、血清学和病毒学方面以横断面的方式描述北美一组明确的 HBV-HIV 患者的特征； 2. 定义长期治疗的益处。我们将通过配对活检和2a纵向确定完全与不完全病毒抑制对临床和血清学结果以及组织学进展的影响。定义与疾病进展相关的 HBV DNA 水平阈值； 2b.与活检相比，建立肝纤维化无创评估的实用性；和2c。确定长期治疗中 TDF 基因型和表型耐药的频率；最后 3. 定义长期治疗的风险。我们将评估基于 TDF 的治疗对 HBV-HIV 队列的长期肾脏和骨骼影响。 总的来说，这项研究将实现 NIH 针对 HBV-HIV 合并感染肝病行动计划中概述的许多关键优先事项。