Detection and Characterization of HIV-1 Intraclade Dual Infection

HIV-1 Intraclade 双重感染的检测和表征

• 批准号: 7568977
• 负责人: David Mitchell Smith
• 金额: $ 17.31万
• 依托单位: VETERANS MEDICAL RESEARCH FDN/SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7568977
• 关键词: Acute; Address; Blood specimen; Characteristics; Chronic; Clinical; Clinical Data; Collaborations; Consequences of HIV; Data; Demographic Analyses; Detection; Disease; Disease Progression; Early treatment; Enrollment; Epidemic; Feline Immunodeficiency Virus; Felis catus; Genetic Processes; Genetic Recombination; HIV; HIV Infections; HIV Seropositivity; HIV drug resistance; HIV-1; Human; Immune system; Incidence; Individual; Infection; Learning; Macaca; Methods; Mono-S; Newly Diagnosed; Participant; Persons; Population; Prevalence; Process; Published Comment; Recording of previous events; Reporting; Research; Risk Factors; SIV; Sampling; Screening procedure; Sexually Transmitted Diseases; Site; Time; United States; Vaccination; Viral; Virus; Virus Diseases; antiretroviral therapy; base; cohort; eligible participant; high risk; intervention program; novel; programs; response; superinfection

DESCRIPTION (provided by applicant): Similar to other chronic viral infections, infection of an individual with a second viral strain (dual infection), also occurs in HIV infection. This proposal aims to determine: (1) novel methods of detecting intraclade dual infection, (2) the incidence and prevalence of dual infection (both coinfection and superinfection) among recently and chronically HIV infected individuals, and (3) the clinical and virologic correlates of dual infection. This proposal is based on a collaboration with the Acute Infection Early Disease Research Program (AIEDRP) network and the San Diego site of the Early Intervention Program (EIP). At UCSD we have available samples from 292 eligible participants from 7 AIEDRP sites for a total of 1224 well-characterized longitudinal samples. From EIP we conservatively estimate to enroll 140 participants over the two years of the study and ultimately have 320 timepoint samples available for dual infection screening. Using new methods for screening, we estimate to identify 55 instances of intraclade dual infection. Demographic and clinical data will also be available from the AIEDRP and EIP cohorts and will be used to determine the correlates associated with intraclade dual infection. We will also generate sequence data from blood samples available from participants identified with dual infection to characterize the virologic processes following dual infection, such as recombination. While not completely analogous to vaccination, the identification and characterization of intraclade dual infections represent a unique opportunity to learn how and why a sensitized immune system fails to protect its host from infection by a very closely related second HIV strain. We project that we will identify and characterize by far the largest cohort of intraclade dual infections reported to date. PUBLIC HEALTH RELEVANCE: Recently, it was discovered that individuals can be infected with HIV more than once. This is often called re-infection or dual infection. We aim to develop new methods for detecting when dual infection has occurred, how often dual infection occurs in a large clinical cohort of people with HIV infection, what are the clinical consequences of HIV dual infection, and evaluate how the two different viral strains interact with each other in the same person following dual infection.

描述（由申请人提供）：类似于其他慢性病毒感染，患有第二个病毒菌株（双重感染）个体的感染也发生在HIV感染中。该建议旨在确定：（1）最近和慢性HIV感染个体的双重感染（共同感染和超感染）的新方法，（2）双重感染（共同感染和超感染）的发生率和流行率，以及（3）双重感染的临床和病毒学相关性。该提案基于与急性感染早期疾病研究计划（AIEDRP）网络的合作和早期干预计划（EIP）的圣地亚哥站点。在UCSD，我们有来自来自7个AIEDRP站点的292名合格参与者的可用样本，共有1224个良好的纵向样品。从EIP开始，我们保守地估计在研究的两年中招募140名参与者，并最终有320个时间点样本可用于双重感染筛查。使用新方法进行筛选，我们估计确定55个双重感染的实例。人口统计学和临床​​数据也将从AIEDRP和EIP队列中获得，并将用于确定与Intaclade双重感染相关的相关性。我们还将从与双重感染的参与者获得的血液样本中生成序列数据，以表征双重感染后的病毒学过程，例如重组。虽然不完全类似于疫苗接种，但鉴定和表征二元感染代表了一个独特的机会，可以学习如何以及为什么通过非常相关的第二HIV菌株保护其宿主免受感染的影响。我们预测，迄今为止，我们将确定并表征迄今为止报告的最大的双重感染队列。 公共卫生相关性：最近，发现个人可以多次感染艾滋病毒。这通常称为重新感染或双重感染。我们旨在开发新的方法来检测何时发生双重感染，双重感染发生在大量的HIV感染患者中，艾滋病毒双重感染的临床后果是什么，并评估两种不同的病毒株如何在双重感染后同一患者中相互相互作用。