Interaction in vivo between HIV and Hepatitis B Virus

描述(申请人提供)：感染HIV-1的人中有10%是乙肝病毒(乙肝)携带者。与HIV-1阴性的乙肝病毒感染者相比，HIV-1感染者患乙肝病毒相关性肝硬变的风险更高，而且两种病毒的混合感染已被证明降低了受感染个体的存活率。随着有效的抗HIV治疗方法的出现，肝脏疾病，特别是乙肝病毒感染，已成为HIV-1和乙肝病毒混合感染者发病和死亡的主要原因。对乙肝病毒的免疫反应仍然缺乏特征性，随着人们对乙肝病毒基因变异的认识日益加深，不同的乙肝病毒基因型之间可能确实存在差异。该项目包括一个重叠多肽文库的应用，该文库旨在量化乙肝病毒特异性T细胞对所有乙肝病毒蛋白、所有人类白细胞抗原(HLA型)和感染主要乙肝病毒基因型别(A-D)的反应。在一项前瞻性研究中，将在乙肝病毒激活的HAART之前和之后的12个月内，在HIV和乙肝病毒共同感染的个体的外周和肝内间隔中表征乙肝病毒特异的反应。这些研究将确定与乙肝病毒清除和/或恶化的肝病相关的新的免疫原性表位。将确定特定的表位和人类白细胞抗原的关联性。病毒动态研究将在乙肝病毒感染者和HIV-1-乙肝病毒混合感染者中进行联合抗乙肝病毒治疗。游离病毒粒子和被感染的肝细胞的半衰期将结合对乙肝病毒特异性T细胞反应的纵向测量来计算。这些研究将允许合理地发展联合抗乙肝治疗或有针对性的免疫调节干预措施，例如治疗性疫苗接种，这可能是成功治疗HIV-1中的乙肝病毒感染所必需的。

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.