HIV Superinfection after Acute and Recent Infection

急性和近期感染后的 HIV 重复感染

• 批准号: 7303505
• 负责人: Robert M. Grant
• 金额: $ 48.03万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7303505
• 关键词: Acceleration; Acute; Address; Affect; Africa; Appearance; Applications Grants; Autologous; Biological; Biological Assay; Brazil; CD4 Positive T Lymphocytes; CD8B1 gene; Case Study; Cell Count; Cells; Clinical; Counseling; Couples; Data; Detection; Disease Progression; Drug resistance; Epidemic; Exposure to; Frequencies; HIV; HIV Infections; HIV-1; Human; Immune; Immune response; Immunity; Infection; Investigation; Knowledge; Laboratory Markers; Measures; Memory; Methods; Monitor; North America; Numbers; Pathogenesis; Patients; Peripheral Blood Mononuclear Cell; Persons; Phenotype; Plasma; Population; Predisposition; Principal Investigator; RNA; Rate; Reporting; Research; Resistance; Risk; San Francisco; Secondary Prevention; Serum; Site; Standards of Weights and Measures; T-Cell Activation; T-Lymphocyte; Testing; Time; Toxic effect; Tropism; Ursidae Family; Variant; Viral; Viral Antigens; Viral Load result; Virulence; Virulent; Virus; antiretroviral therapy; base; cell mediated immune response; cohort; comparison group; design; drug resistant virus; experience; falls; fitness; in vivo; preference; programs; response; social; superinfection; vaccine development; vector; virus genetics

PROJECT 3: Superinfection, or sequential acquisition of HIV variants, could spread viruses that are more drug-resistant or more virulent. The circumstances that govern susceptibility to superinfection are not known, and may differ in subtype B epidemics (like that in North America) compared with epidemics in Africa. A better understanding of superinfection risk, consequences, and biological determinants will help guide counseling of infected persons and may provide clues to protective immunity and HIV pathogenesis. Available case reports indicate that superinfection has occurred primarily in recent seroconverters. Using the same detection methods, superinfection was not observed in large cohorts of persons with established infections. We now propose to extend our research on superinfection to recently infected persons, who appear to have higher risk. We will specifically test the hypothesis that superinfection risk decreases over the course of HIV infection (aim1a) despite increases in exposure to HIV-1-infected partners (aim1b). Our findings suggest that serosorting, or preference for partners having the same serostatus, increases with increased duration of infection. The power to detect superinfection cases is enhanced by combining cohorts in San Francisco and Southeastern Brazil. We also will determine if superinfection, or dual infection, is associated with acceleration in disease progression, as indicated by plasma RNA level, CD4 T cell counts, T cell activation, and naive and memory subset analysis (aim 2). Inclusion of persons with multiple baseline infections helps assure power for analysis of laboratory markers of disease progression. We will also investigate biological mechanisms that may determine superinfection risk (aim 3). We will specifically test the hypotheses that superinfecting viruses may have greater replication capacity, greater fusion capacity, broader tropism, or increased capacity to escape from autologous serum neutralization or cell-mediated immune responses (in coordination with Project 4). To extend our recent findings, we will determine if serum neutralization responses become broader over time in a manner that correlates with superinfection risk. Viral phenotypes will be assessed using whole virus and viral test vectors. This project will fill important gaps in knowledge about superinfection and dual infection, which bear directly on the epidemic spread ofHIV, protective immunity, secondary prevention, and HIV pathogenesis.

项目3：重复感染，或连续获得艾滋病毒变体，可以传播更多的病毒， 抗药性或毒性更强控制重复感染易感性的环境尚不清楚， 并且与非洲的流行病相比，亚型B流行病（如北美）可能有所不同。一 更好地了解重复感染的风险、后果和生物决定因素将有助于指导 为感染者提供咨询，并可能提供保护性免疫和HIV发病机制的线索。 现有的病例报告表明，重叠感染主要发生在最近的血清转换。使用 同样的检测方法，在已建立的感染者的大队列中没有观察到重复感染。 感染.我们现在建议将我们对双重感染的研究扩展到最近感染的人， 似乎有更高的风险。我们将专门检验重复感染风险随时间推移而降低的假设。 HIV感染（aim 1a）的过程，尽管暴露于HIV-1感染的伴侣（aim 1b）增加。我们 研究结果表明，血清分选，或具有相同血清状态的伴侣的偏好， 感染持续时间延长。通过合并队列提高了检测重叠感染病例的能力 在旧金山弗朗西斯科和巴西东南部。我们还将确定是否重叠感染，或双重感染， 与疾病进展加速相关，如血浆RNA水平、CD 4 T细胞计数、T细胞亚群、 细胞活化以及幼稚和记忆亚群分析（AIM 2）。纳入具有多项基线的人员 感染有助于确保分析疾病进展的实验室标志物的能力。我们还将 调查可能决定双重感染风险的生物机制（目标3）。我们将专门测试 假设重复感染病毒可能具有更大的复制能力，更大的融合能力， 更广泛的向性，或逃避自体血清中和或细胞介导的能力增加 免疫反应（与项目4协调）。为了扩展我们最近的发现，我们将确定血清是否 中和反应以与重复感染风险相关的方式随着时间的推移而变得更广泛。病毒 将使用全病毒和病毒测试载体评估表型。该项目将填补重要空白， 对双重感染和重叠感染的认识，直接关系到HIV的流行传播， 保护性免疫、二级预防和HIV发病机制。