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

 描述(由申请人提供)：与乙肝病毒(乙肝病毒)混合感染在艾滋病毒感染者中很常见。HIV加速了乙肝病毒相关性肝纤维化的进展，与单独感染HIV或乙肝病毒的患者相比，HIV/乙肝患者罹患终末期肝病(ESLD)和肝细胞癌(HCC)的风险更高。因此，这些肝脏并发症是艾滋病毒/乙肝患者发病率和死亡率的主要原因。为了减少这些事件的风险，建议对所有艾滋病毒/乙肝患者进行抗乙肝病毒活性抗逆转录病毒疗法(ART)，最好是使用替诺福韦，目的是将这两种病毒抑制到无法检测到的水平。尽管使用了以替诺福韦为基础的抗逆转录病毒疗法，但艾滋病毒/乙肝患者的肝脏并发症发生率仍然很高。此外，在临床实践中，很大比例的艾滋病毒/乙肝患者很难完全抑制乙肝病毒，可检测到的乙肝病毒，以及艾滋病毒病毒血症，可能是这一组观察到的ESLD和肝细胞癌高发病率的重要因素。因此，需要对使用替诺福韦为基础的抗逆转录病毒疗法的艾滋病毒/乙肝患者进行足够有力的队列研究，以确定这些患者肝脏并发症的机制。对HIV/HBV患者的研究一直受到样本量小、随访时间短、重要变量收集不足的限制，并且尚未评估ESLD或肝细胞癌等临床终点。这项建议将通过利用北美艾滋病队列研究与设计合作(NA-ACCORD)的数据来解决这些知识差距和现有限制，以创建最大的艾滋病毒/乙肝患者队列，并评估已通过医疗记录审查确认的ESLD和HCC事件。在这一应用中，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HBVDNA和HIV RNA对接受以替诺福韦为基础的抗逆转录病毒治疗的HIV/HBV患者肝脏并发症的影响。目的1将确定在接受替诺福韦抗逆转录病毒治疗的艾滋病毒/乙肝患者中，与可检测到的HBVDNA相关的由ESLD和肝细胞癌事件定义的肝脏并发症的风险。目标2将量化三个个体合并艾滋病毒病毒血症的肝脏并发症的风险。我们的分析还将确定这些患者肝脏事件的其他重要决定因素(例如，CD4计数不足、肥胖、糖尿病、危险饮酒)。这些目标的完成将填补艾滋病毒/乙肝患者在肝脏并发症机制方面的关键知识空白。如果我们的假设得到证实，并且可检测到的乙肝病毒和艾滋病毒病毒血症被确定为导致不良肝脏结局的重要因素，则需要开发和评估干预措施，以提高对这些病毒的完全抑制率。这些发现将激励关于艾滋病毒感染患者的最佳乙肝治疗策略的新的研究建议，这可能改变艾滋病毒中乙肝病毒管理的临床范例。

 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.