Acute HIV infection and pregnancy

急性艾滋病毒感染和怀孕

• 批准号: 8072942
• 负责人: Manhattan E Charurat
• 金额: $ 29.28万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8072942
• 关键词: Accounting; Acute; Address; Affect; Africa; African; Algorithms; Anti-Retroviral Agents; Antibodies; Attention; Biological; Biological Assay; Breast Feeding; Child; Clinical; Cross-Sectional Studies; Development; Diagnosis; Disease; Enrollment; Epidemiology; Estrogens; Female of child bearing age; Frequencies; Future; Genital system; Genome; Goals; HIV; HIV Infections; Human Virology; Immune response; Immunologics; Incidence; Individual; Infant; Infection; Institutes; Knowledge; Link; Maryland; Measures; Mothers; Natural History; Nigeria; Nucleic Acid Amplification Tests; Pathogenesis; Predisposition; Pregnancy; Pregnant Women; Prevention; Probability; Progesterone; Prophylactic treatment; Relative (related person); Research; Research Personnel; Research Project Grants; Risk; Sampling; Screening procedure; Sequence Analysis; Series; Staging; Testing; Universities; Vagina; Vertical Disease Transmission; Viral; Viral Load result; Viremia; Virus; Woman; base; disease natural history; experience; genetic selection; high risk; in utero; indexing; neutralizing antibody; pregnant; programs; public health relevance; public health research; repository; scale up; transmission process; virus host interaction

DESCRIPTION (provided by applicant): A collaborative team involving investigators led by the Institute of Human Virology-University of Maryland (IHV) will identify 115 pregnant women with acute HIV infection. Our long-term goal is to advance the understanding of mother-to-child transmission (MTCT) risk in women who acquired HIV infection during pregnancy. Employing a combination of rapid HIV assays and multi-stage pooled nucleic acid amplification tests, pregnant women from Nigeria will be enrolled during the window of viral antigenemia and prior to development of confirmatory antibodies positivity. This research extends the knowledge of early host-virus interaction to address the specific prevention needs within the context of the prevention of MTCT (PMTCT). We hypothesize that acute HIV infection among pregnant women is underestimated within the setting of PMTCT program and is characterized by its association with vaginal infections that are under-diagnosed during pregnancy. Maternal acute HIV infection could increase the risk of MTCT and affect viral selection compared to long-standing HIV infection. The unique HIV subtypes in Nigeria characterized predominantly by subtype G and CRF02_AG could also alter the transmission risk. To test these interlocking hypotheses, we propose to: (1) determine the incidence rate and correlates of acute HIV infection among pregnant women, (2) evaluate the associations between acute HIV infection, HIV subtypes, and mother-to-child transmission, and (3) use single genome amplification to compare the level of genetic selection present in MTCT in relations to acute and long-standing maternal HIV infection. While compelling evidences suggest the potential importance of detecting incident maternal HIV infection, remarkably little attention has been devoted to this goal. Not surprisingly, MTCT during acute HIV and its relation to the effect of antiretroviral prophylaxis has not been evaluated. This proposal will provide a unique view of secondary HIV infection (i.e. from an acutely infected index case to a susceptible individual) within the context of mother-to-child transmission and of pathogenesis including early host-virus interactions. It also tackles the issue of "missed opportunity" for prevention directed at pregnant women with acute infection that would otherwise be missed by conventional antibody-based testing strategies. Lastly, very early recognition may allow for HIV treatment that could alter the natural history of the disease. All in all, this proposal will permit exciting epidemiological, clinical, and public health research opportunities. PUBLIC HEALTH RELEVANCE: This study is to advance the understanding of mother-to-child HIV transmission risk in women who acquired HIV infection during pregnancy.

描述（由申请人提供）：由马里兰大学人类病毒学研究所 (IHV) 领导的研究人员组成的合作小组将鉴定 115 名患有急性 HIV 感染的孕妇。我们的长期目标是增进对怀孕期间感染艾滋病毒的妇女的母婴传播 (MTCT) 风险的了解。采用快速艾滋病毒检测和多阶段汇总核酸扩增检测相结合的方法，来自尼日利亚的孕妇将在病毒抗原血症窗口期和确认性抗体呈阳性之前进行招募。这项研究扩展了早期宿主与病毒相互作用的知识，以满足预防母婴传播 (PMTCT) 背景下的特定预防需求。我们假设，在预防母婴传播计划的背景下，孕妇的急性艾滋病毒感染被低估，其特点是其与妊娠期间未得到充分诊断的阴道感染的相关性。与长期感染艾滋病毒相比，母亲急性艾滋病毒感染可能会增加母婴传播的风险，并影响病毒选择。尼日利亚独特的 HIV 亚型（主要为 G 亚型和 CRF02_AG）也可能改变传播风险。为了检验这些相互关联的假设，我们建议：（1）确定孕妇中急性艾滋病毒感染的发病率和相关性，（2）评估急性艾滋病毒感染、艾滋病毒亚型和母婴传播之间的关联，以及(3) 使用单基因组扩增来比较母婴传播中存在的遗传选择水平与急性和长期孕产妇艾滋病毒感染的关系。尽管有令人信服的证据表明检测孕产妇艾滋病毒感染事件的潜在重要性，但人们对这一目标的关注却少之又少。毫不奇怪，急性艾滋病毒期间的母婴传播及其与抗逆转录病毒预防效果的关系尚未得到评估。该提案将在母婴传播和发病机制（包括早期宿主病毒相互作用）的背景下提供继发性艾滋病毒感染（即从急性感染指示病例到易感个体）的独特观点。它还解决了针对患有急性感染的孕妇“错失预防机会”的问题，否则传统的基于抗体的检测策略可能会错过这些机会。最后，早期识别可能有助于艾滋病毒治疗，从而改变该疾病的自然史。总而言之，该提案将提供令人兴奋的流行病学、临床和公共卫生研究机会。公共卫生相关性：本研究旨在增进对怀孕期间感染艾滋病毒的妇女的母婴艾滋病毒传播风险的了解。