Interaction in vivo between HIV and Hepatitis B Virus

描述（由申请人提供）：10%的HIV-1感染者是B型肝炎病毒（HBV）携带者。与HIV-1阴性的HBV感染者相比，HIV-1感染者发生HBV相关肝硬化的风险更高，同时感染两种病毒已被证明会降低受影响个体的生存率。随着有效抗HIV治疗的出现，肝脏疾病，特别是HBV感染，已成为HIV-1-HBV合并感染者发病和死亡的主要原因。对HBV的免疫应答特征仍然不清楚，随着对HBV遗传变异的认识的增加，HBV基因型之间可能确实存在差异。该项目包括重叠肽库的应用，该重叠肽库旨在量化HBV特异性T细胞对所有HBV蛋白、所有HLA类型和主要HBV基因型（A-D）感染的应答。在一项前瞻性研究中，HBV特异性应答将在HBV活性HAART前和随后12个月内在HIV-HBV共感染个体的外周和肝内室中进行表征。这些研究将确定与HBV清除和/或肝病恶化相关的新免疫原性表位。 将鉴定特异性表位和HLA相关性。将在HBV感染和HIV-1-HBV合并感染个体中进行联合抗HBV治疗的病毒动力学研究。结合HBV特异性T细胞应答的纵向测量，计算游离病毒体和感染肝细胞的半衰期。这些研究将允许合理开发联合抗HBV治疗或靶向免疫调节干预措施，如治疗性疫苗接种，这可能是成功治疗HIV-1背景下HBV感染所必需的。

DESCRIPTION (provided by applicant): Ten percent of individuals infected with HIV-1 infection are carriers of hepatitis B virus (HBV). Patients with HIV-1 infection have a higher risk of HBV-related cirrhosis than HIV-1-negative-HBV-infected individuals, and co-infection with both viruses has been shown to decrease survival in affected individuals. With the advent of effective anti-HIV therapy, liver disease and particularly HBV infection, has become a major cause of morbidity and mortality in HIV-1-HBV co-infected individuals. The immune response to HBV remains poorly characterized and with increasing recognition of the genetic variation of HBV, may indeed differ between HBV genotypes. This project includes the application of an overlapping peptide library designed to quantify HBV-specific T cell responses to all HBV proteins, in all HLA types and with infection of the major HBV genotypes (A-D). HBV-specific responses will be characterized in the peripheral and intra-hepatic compartments of HIV-HBV co-infected individuals prior to HBV-active HAART and over the following 12 months in a prospective study. These studies will identify new immunogenic epitopes associated with HBV clearance and/or worsening liver disease. The specific epitope and HLA association will be identified. Viral dynamic studies will be performed with combination anti-HBV therapy in HBV-infected and HIV-1-HBV co-infected individuals. The half lives of free virions and infected hepatocytes will be calculated in combination with the longitudinal measurement of HBV-specific T cell responses. These studies will allow the rational development of combination anti-HBV therapy or targeted immunomodulatory interventions, such as therapeutic vaccination, that may be necessary for successful treatment of HBV infection in the setting of HIV-1.