Early and acute HIV-1 subtype C infection in Botswana

博茨瓦纳的早期急性 HIV-1 C 亚型感染

• 批准号: 6765109
• 负责人: VLADIMIR A NOVITSKY
• 金额: $ 18.9万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6765109
• 关键词: Africa; HIV infections; acute disease /disorder; cellular immunity; clinical research; cytokine; cytotoxic T lymphocyte; disease /disorder classification; disease /disorder onset; enzyme linked immunosorbent assay; flow cytometry; helper T lymphocyte; human immunodeficiency virus 1; human subject; longitudinal human study; molecular cloning; nucleic acid sequence; plasma; polymerase chain reaction; virus genetics; virus infection mechanism; virus replication

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.

描述（由申请人提供）：HIV-1亚型C（HIV-1C）是AIDS流行中的主要HIV-1亚型。急性HIV-1C感染中的早期病毒学和免疫学事件尚不清楚。预计将提供非毒性免疫力的疫苗候选者的功效目标是减少急性感染阶段的HIV复制量。从HIV疫苗设计的角度来看，了解急性HIV-1C感染中病毒学和免疫学参数之间的关联至关重要。当前的试点建议的目的是在HIV-1C感染中尽早确定个体，并在急性HIV-1C感染中表征病毒和免疫参数。 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％。在适当的情况下，将提交更全面的RO1应用，以调查急性HIV-1C感染。这项研究有两个具体的目标。这项研究的第一个具体目的是分析急性HIV-1C感染中病毒负荷（血浆和前病毒和病毒遗传多样性）之间的潜在趋势。这些数据应表明急性HIV-1C感染中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，血浆病毒载量以及与细胞相关的前病毒载荷定量，PCR扩增，克隆和测序。第二个特定目的是针对急性HIV-1C感染中细胞免疫反应的表征，以及与病毒设定点相关的免疫学参数的鉴定。将分析病毒特异性CD4+和CD8+ T细胞免疫反应的大小，广度和多样性。免疫学方法将包括IFN-Gamma-Elispot测定法和使用四色FACSCALIBUR流式细胞仪的细胞内细胞因子染色。