Early and acute HIV-1 subtype C infection in Botswana

描述（由申请人提供）：HIV-1亚型C（HIV-1C）是艾滋病流行中的主要HIV-1亚型。急性HIV-1C感染的早期病毒学和免疫学事件尚不清楚。预期产生非灭菌免疫的候选疫苗的效力的最低目标是减少感染急性期期间HIV复制的量。从HIV疫苗设计和选择相关HIV疫苗试验终点的角度来看，了解急性HIV-1C感染中病毒学和免疫学参数之间的相关性至关重要。目前的试验性建议的目的是尽早识别HIV-1C感染者，并确定急性HIV-1C感染者的病毒和免疫参数。这项探索性的R21研究被设计为HIV疫苗准备研究（HVTN方案903）的扩展，该研究是一项前瞻性队列研究，于2003年初在博茨瓦纳开始，共有500名HIV感染高危的未感染者参加。这项研究将利用博茨瓦纳的流行病学和实验室基础设施，博茨瓦纳是一个南部非洲国家，估计艾滋病毒流行率约为35- 40%。在适当情况下，将提交更全面的RO 1申请，以调查急性HIV-1C感染。本研究有两个具体目的。本研究的第一个具体目的是分析急性HIV-1C感染中病毒载量（血浆和前病毒）与病毒遗传多样性之间的潜在趋势。这些数据应表明急性HIV-1C感染的病毒学参数与病毒设定点之间的潜在关系。病毒学方法将包括DNA和RNA分离、血浆病毒载量和细胞相关前病毒载量定量、PCR扩增、克隆和测序。第二个特定目标旨在表征急性HIV-1C感染中的细胞免疫应答，并鉴定与病毒设定点相关的免疫学参数。将分析急性HIV-1C感染中病毒特异性CD 4+和CD 8 + T细胞免疫应答的幅度、广度和多样性。免疫学方法将包括IFN-γ-ELISPOT测定和使用四色FACSCalibur流式细胞仪的细胞内细胞因子染色。

DESCRIPTION (provided by applicant): HIV-1 subtype C (HIV-1C) is the dominant HIV-1 subtype in the AIDS epidemic. Early virological and immunological events in acute HIV-1C infection are not well understood. A minimal goal for efficacy with a vaccine candidate that is expected to give non-sterilizing immunity would be to reduce the amount of HIV replication during the acute stage of infection. Understanding associations between virological and immunological parameters in acute HIV-1C infection will be critical from the perspective of HIV vaccine design and for the selection of pertinent HIV vaccine trial endpoints. The purpose of the current pilot proposal is to identify individuals as early as possible in HIV-1C infection and characterize viral and immune parameters in acute HIV-1C infection. This exploratory R21 study is designed as an extension to the HIV Vaccine Preparedness Study (HVTN Protocol 903), a prospective cohort study of 500 uninfected individuals at high risk for HIV infection to start in Botswana in early 2003. This study will utilize the epidemiologic and laboratory infrastructure in place in Botswana, a country in southern Africa with an estimated HIV prevalence of about 35-40%. A more comprehensive RO1 application to investigate acute HIV-1C infection will be submitted when appropriate. There are two Specific Aims in this study. The first Specific Aim of this study is to analyze potential trends between viral load (both plasma and proviral) and viral genetic diversity in acute HIV-1C infection. These data should indicate a potential relationship between virological parameters in acute HIV-1C infection and viral set point. Virological methods will include DNA and RNA isolation, plasma viral load and cell-associated proviral load quantification, PCR amplification, cloning, and sequencing. The second Specific Aim targets the characterization of cellular immune responses in acute HIV-1C infection and the identification of immunological parameters that correlate with viral set point. The magnitude, breadth, and diversity of virus-specific CD4+ and CD8+ T-cell immune responses in acute HIV-1Cinfection will be analyzed. Immunological methods will include IFN-gamma-ELISPOT assay and intracellular cytokine staining using the four-color FACSCalibur flow cytometer.