Acute HIV infection and pregnancy

描述（由申请人提供）：由马里兰州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确定115名急性HIV感染的孕妇。我们的长期目标是提高对怀孕期间感染艾滋病毒的妇女的母婴传播风险的认识。采用快速HIV检测和多阶段合并核酸扩增检测相结合的方法，将在病毒抗原血症窗口期和确证性抗体阳性之前入组来自尼日利亚的妊娠女性。这项研究扩展了早期宿主-病毒相互作用的知识，以解决预防母婴传播（PMTCT）背景下的具体预防需求。我们假设，急性艾滋病毒感染孕妇被低估的PMTCT程序的设置内，其特点是与阴道感染，在怀孕期间诊断不足。与长期HIV感染相比，母亲急性HIV感染可增加母婴传播的风险并影响病毒选择。尼日利亚独特的艾滋病毒亚型主要以G亚型和CRF02_AG为特征，也可能改变传播风险。为了验证这些相互关联的假设，我们建议：（1）确定孕妇中急性HIV感染的发病率和相关因素，（2）评估急性HIV感染、HIV亚型和母婴传播之间的关联，（3）使用单基因组扩增来比较母婴传播中存在的与急性和长期母体HIV感染相关的遗传选择水平。虽然令人信服的证据表明，检测事件孕产妇艾滋病毒感染的潜在重要性，非常少的注意力一直致力于这一目标。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。这项建议将提供一个独特的观点，二次艾滋病毒感染（即从一个急性感染的索引病例易感个体）的背景下，母婴传播和发病机制，包括早期宿主病毒的相互作用。它还解决了针对急性感染孕妇的预防“错失机会”的问题，否则传统的基于抗体的检测战略就会错过这种机会。最后，早期识别可能有助于艾滋病毒治疗，从而改变疾病的自然史。总而言之，这项提案将为流行病学、临床和公共卫生研究提供令人兴奋的机会。公共卫生相关性：本研究旨在提高对妊娠期感染HIV妇女母婴传播风险的认识。

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.