Risk of Liver Complications with HBV and HIV Viremia During Tenofovir-Based ART

 描述（由申请人提供）：在HIV感染患者中，合并感染B型肝炎病毒（HBV）很常见。HIV加速HBV相关肝纤维化的进展，HIV/HBV患者比仅感染HIV或HBV的患者发生终末期肝病（ESLD）和肝细胞癌（HCC）的风险更高。因此，这些肝脏并发症是HIV/HBV患者发病和死亡的主要原因。为了降低这些事件的风险，建议对所有HIV/HBV患者进行抗HBV活性抗逆转录病毒治疗（ART），最好使用替诺福韦，目标是将这两种病毒抑制到无法检测的水平。尽管使用基于替诺福韦的ART，但HIV/HBV患者的肝脏并发症发生率仍然很高。此外，在临床实践中，很大比例的HIV/HBV患者不容易实现完全的HBV抑制，可检测到的HBV，沿着HIV病毒血症，可能是在该组中观察到的高ESLD和HCC发生率的重要因素。因此，需要对接受替诺福韦为基础的ART的HIV/HBV患者进行有说服力的队列研究，以确定这些患者肝脏并发症的机制。HIV/HBV患者的研究受到样本量小、随访时间短、重要变量收集不充分的限制，并且尚未评估临床终点，如ESLD或HCC。该提案将通过利用北美艾滋病队列研究与设计合作组织（NA-ACCORD）的数据来解决这些知识差距和现有限制，以创建最大的HIV/HBV患者队列，并评估已通过病历审查确认的ESLD和HCC事件。在本申请中，我们将使用NA-ACCORD的独特数据进行一系列流行病学研究，以评估可检测到的HBV DNA和HIV RNA对接受替诺福韦抗逆转录病毒治疗的HIV/HBV患者肝脏并发症的影响。目的1将确定接受替诺福韦抗逆转录病毒治疗的HIV/HBV患者中与可检测到HBV DNA相关的肝脏并发症（定义为ESLD和HCC事件）的风险。目的2将量化三个个体中HIV病毒血症的肝脏并发症的风险。我们的分析还将确定肝脏事件的其他重要决定因素（例如，低CD 4计数，肥胖，糖尿病，危险的酒精使用）。这些目标的完成将解决艾滋病毒/乙型肝炎患者肝脏并发症机制的关键知识差距。如果我们的假设得到证实，并且可检测的HBV和HIV病毒血症被确定为肝脏不良结局的重要贡献者，则需要开发和评估干预措施以提高这些病毒的完全抑制率。这些发现将激发新的研究建议，在艾滋病毒感染者的最佳HBV治疗策略，可能会改变在艾滋病毒的HBV管理的临床模式。

 DESCRIPTION (provided by applicant): Coinfection with hepatitis B virus (HBV) is common among HIV-infected patients. HIV accelerates the progression of HBV-related liver fibrosis, and HIV/HBV patients have higher risks of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) than those with HIV or HBV alone. As a result, these liver complications are major causes of morbidity and mortality in HIV/HBV patients. To reduce the risks of these events, anti-HBV-active antiretroviral therapy (ART), preferably with tenofovir, is recommended in all HIV/HBV patients with the goal of suppressing both viruses to undetectable levels. Despite the use of tenofovir-based ART, rates of liver complications remain high among HIV/HBV patients. Further, complete HBV suppression is not readily achieved in a large proportion of HIV/HBV patients in clinical practice, and detectable HBV, along with HIV viremia, may be important contributors to the high rates of ESLD and HCC observed in this group. Adequately powered cohort studies of HIV/HBV patients on tenofovir-based ART are therefore needed to determine the mechanisms for liver complications in these individuals. Studies of HIV/HBV patients have been limited by small sample sizes, short follow-up, inadequate collection of important variables, and have not evaluated clinical endpoints such as ESLD or HCC. This proposal will address these knowledge gaps and existing limitations by utilizing data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) to create the largest cohort of HIV/HBV patients and evaluate ESLD and HCC events that have been confirmed by medical record review. In this application, we will use the unique data of the NA-ACCORD to conduct a series of epidemiologic studies to evaluate the impact of detectable HBV DNA and HIV RNA on liver complications in HIV/HBV patients receiving tenofovir-based antiretroviral therapy. Aim 1 will determine the risk of liver complications, defined by ESLD and HCC events, associated with detectable HBV DNA among HIV/HBV patients on tenofovir-based antiretroviral therapy. Aim 2 will quantify the risk of liver complications with HIV viremia in thee individuals. Our analyses will also identify other important determinants of liver events (e.g., lo CD4 count, obesity, diabetes, hazardous alcohol use) in these patients. The completion of these aims will address critical knowledge gaps on the mechanisms of liver complications among HIV/HBV patients. If our hypotheses are confirmed and detectable HBV and HIV viremia are identified as important contributors to adverse hepatic outcomes, interventions would need to be developed and evaluated to increase rates of complete suppression of these viruses. These findings will motivate new research proposals on optimal HBV treatment strategies in HIV-infected patients that may change the clinical paradigm for HBV management in HIV.