HIV IN SEMEN-EFFECTS OF STDS AND ANTIVIRAL THERAPY

精液中的艾滋病毒——性传播疾病和抗病毒治疗的影响

• 批准号: 7920650
• 负责人: MYRON Scott COHEN
• 金额: $ 7.84万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7920650
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Antiviral Therapy; Area; Behavioral; Biological; Biological Assay; Biology; Blood; CD4 Positive T Lymphocytes; Caring; Cells; Cellular Immunity; Client; Clinic; Cohort Studies; Collaborations; Data; Detection; Development; Enrollment; Event; Evolution; Exposure to; Female; Fluorescent in Situ Hybridization; Genital system; HIV; HIV Infections; Human immunodeficiency virus test; Immune response; Infection; Lead; Letters; Lymphocyte; Malawi; Methods; Monitor; Mutation; Myron; Patients; Persons; Prevention; Prevention strategy; RNA; Recruitment Activity; Research Institute; Research Personnel; Risk; Role; Seminal; Seminal Plasma; Seminal fluid; Sexual Partners; Sexual Transmission; Testing; Time; Vaccine Research; Variant; Viral; Viral Load result; Vision; Woman; Work; care seeking; cell mediated immune response; cohort; enzyme linked immunospot assay; falls; genital secretion; high risk men; improved; insight; male; men; novel; prevent; programs; response; transmission process

DESCRIPTION (provided by applicant): For the past 10 years we have focused on the biology of HIV in semen. Most recently we have used a novel HIV RNA detection strategy to identify people with acute HIV infection. We found that acute HIV infections are remarkably frequent in patients in our STD clinic in Malawi (>2% of all clients, AIDS, 2004). Such patients excrete so much HIV in semen that secondary sexual transmission becomes extremely likely. This renewal Application includes detailed studies of acute HIV infection in Malawi. In Aim I we will recruit a longitudinal cohort of more than 200 men and women with acute HIV infection, and some of their sexual partners. We will evaluate the ability of simplified testing strategies to identify people with acute HIV infection. In Aim II we will examine the dynamics of HIV replication in blood and semen to test the hypothesis that the concentration of HIV in semen decreases faster and to a lower level in semen than in blood. We will examine the degree of HIV viral diversity in seminal plasma at the time of transmission, and monitor viral change(s) over time. We will use the heteroduplex tracking assay (HTA) for this purpose. We will use fluorescence in-situ hybridization (FISH) to determine the number of seminal cells infected, and the number of HIV variants per cell. We will determine the infection status of sexual partners, and compare the HIV variants in concordant partners. In Aim III we will examine the temporal CTL response in patients with acute infection. This response should predict the magnitude of viral burden over time, and the sight(s) of viral mutation. We will examine the CTL response in both HIV postive and negative sexual partners. We will use ELISPOT assays to examine the CTL response in seminal CDS cells. We will undertake prevention efforts directed at HIV negative partners, who are at considerable risk for HIV acquisition. We believe the studies proposed in this Application will provide unique insight into the biology of acute HIV infection and HIV transmission, and information critical for both biological and behavioral prevention strategies.

描述（由申请人提供）：在过去的10年中，我们一直专注于精液中的艾滋病毒生物学。最近，我们使用了一种新型的HIV RNA检测策略来识别患有急性HIV感染的人。我们发现，在我们在马拉维的性病诊所中，急性HIV感染非常常见（> 2％的所有客户，AIDS，2004年）。这样的患者在精液中排泄了太多的艾滋病毒，以至于继发性传播极有可能。该更新应用包括马拉维急性HIV感染的详细研究。在目标上，我将招募200多名患有急性艾滋病毒感染的男人和女人的纵向人群，以及他们的一些性伴侣。我们将评估简化测试策略鉴定急性HIV感染的人的能力。在AIM II中，我们将检查血液和精液中HIV复制的动力学，以检验以下假设：精液中HIV的浓度比血液中的hiv浓度更快，而精液的水平更快，并且较低。我们将在传播时检查精囊血浆中的HIV病毒多样性程度，并随着时间的推移监测病毒变化。为此，我们将使用HeteroDuplex跟踪测定法（HTA）。我们将使用荧光原位杂交（FISH）来确定感染的精液细胞数量以及每个细胞的HIV变体数量。我们将确定性伴侣的感染状况，并比较一致伴侣中的艾滋病毒变体。在AIM III中，我们将检查急性感染患者的时间CTL反应。这种反应应预测随着时间的流逝和病毒突变的视力，病毒负担的幅度。我们将研究HIV Postive和负面性伴侣中的CTL反应。我们将使用ELISPOT分析检查精确CDS细胞中的CTL响应。我们将承担针对艾滋病毒负面伴侣的预防工作，这些伴侣面临着艾滋病毒收购风险的相当大的风险。我们认为，本应用中提出的研究将为急性HIV感染和HIV传播的生物学提供独特的见解，以及对生物和行为预防策略至关重要的信息。