Acute HCV Infection in Injection Drug Users

描述(由申请人提供)：拟议的多学科研究将研究街头招募的注射吸毒者中急性丙型肝炎病毒(丙型肝炎病毒)感染的临床、病毒学和免疫学特征。对100名未感染丙型肝炎病毒的注射人群进行前瞻性跟踪调查。一种高灵敏的转录介导扩增(TMA)方法将用于检测两周一次的血浆标本中的丙型肝炎病毒RNA。根据我们在研究社区中观察到的丙型肝炎发病率，我们估计我们将观察到多达70例新感染。这些感染的临床、病毒学和免疫学研究将联合进行，以确定静脉吸毒者的原发丙型肝炎病毒感染的特征，并评估与成功的免疫反应和病毒清除相关的临床、免疫学和病毒学特征，拟议研究的目的是：(1)通过前瞻性观察临床和实验室特征的谱、早期感染的病毒动力学、自发清除感染的比例和清除时间，描述街头招募的活跃注射吸毒者急性丙型肝炎病毒感染的自然历史；(2)研究丙型肝炎病毒特异性细胞免疫应答在急性丙型肝炎病毒感染中的演变，包括丙型肝炎病毒表位特异性、前体频率、表型、细胞因子谱、增殖和细胞毒性；(3)与病毒学事件平行研究丙型肝炎病毒特异性细胞免疫应答的动力学和功能，比较感染清除和进展为慢性感染的静脉吸毒者，以确定成功的丙型肝炎免疫应答的特征。

DESCRIPTION (provided by applicant): The proposed multidisciplinary study will examine the clinical, virologic and immunologic characteristics of acute hepatitis C virus (HCV) infection among street-recruited injection drug users (IDUs). A cohort of 100 HCV-uninfected IDUs will be followed prospectively. A highly sensitive transcription-mediated-amplification (TMA) assay will be used to detect HCV RNA in biweekly plasma specimens. Based on the HCV incidence rates we have observed in the study community, we estimate that we will observe as many as 70 new infections. Clinical, virologic, and immunologic studies of these infections will be conducted in concert, to characterize primary HCV infections among IDUs, and to assess clinical, immunologic, and virologic characteristics associated with successful immune responses and viral clearance, The aims of the proposed study are to: (1) describe the natural history of acute HCV infection in street-recruited, active IDUs by prospectively observing the spectrum of clinical and laboratory features, the viral kinetics of early infection, the proportion who spontaneously clear infection, and the timing of clearance; (2) characterize the evolution of HCV-specific cellular immune responses in acute HCV infection, including the HCV epitope specificity, precursor frequency, phenotype, cytokine profile, proliferation and cytotoxicity of HCV-specific T-cells; and (3) study the kinetics and function of HCV-specific cellular immune responses in parallel with the virologic events, comparing IDUs whose infection is cleared with those who progress to chronic infection, to determine the characteristics of a successful immune response to HCV.