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。一种有望提供非灭菌性免疫的候选疫苗的功效的最小目标是减少感染急性阶段的艾滋病毒复制量。了解急性HIV- 1c感染的病毒学和免疫学参数之间的关联，对于HIV疫苗设计和相关HIV疫苗试验终点的选择至关重要。目前试点方案的目的是尽早识别HIV-1C感染的个体，并表征急性HIV-1C感染的病毒和免疫参数。这项探索性R21研究旨在作为艾滋病毒疫苗准备研究（HVTN议定书903）的延伸，该研究是一项对500名艾滋病毒感染高风险未感染者的前瞻性队列研究，将于2003年初在博茨瓦纳开始。这项研究将利用博茨瓦纳现有的流行病学和实验室基础设施，博茨瓦纳是非洲南部的一个国家，估计艾滋病毒流行率约为35-40%。在适当的时候，将提交更全面的RO1申请来调查急性HIV-1C感染。本研究有两个具体目的。本研究的第一个特定目的是分析急性HIV-1C感染中病毒载量（血浆和原病毒）和病毒遗传多样性之间的潜在趋势。这些数据应该表明急性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的前病毒载量定量，PCR扩增，克隆和测序。第二个特异性目标是急性HIV-1C感染的细胞免疫反应的特征和与病毒设定点相关的免疫参数的鉴定。将分析急性hiv -1感染中病毒特异性CD4+和CD8+ t细胞免疫反应的幅度、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流式细胞仪进行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.