EPIDEMIOLOGY/MOLECULAR VIROLOGY OF ORAL HIV TRANSMISSION

艾滋病毒口腔传播的流行病学/分子病毒学

• 批准号: 6498081
• 负责人: Timothy W Schacker
• 金额: $ 32.33万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2003-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6498081
• 关键词: HIV infections; T lymphocyte; biopsy; blood chemistry; clinical research; communicable disease transmission; disease /disorder proneness /risk; enzyme linked immunosorbent assay; epidemiology; human immunodeficiency virus; human subject; immunocytochemistry; in situ hybridization; longitudinal human study; oral mucosa; oral pharyngeal; pathologic process; semen; tissue /cell culture; virus RNA; western blottings

There is limited data to assess the true risk of unprotected oral- genital contact for acquisition Of HIV infection. Animal data suggests of tonsil tissue can be easily infected with SIV and some observational studies suggest the rate of oral transmission may be as high as 20-25% among men who have sex with other men. However there are no data to estimate risk for heterosexual oral-genital contact. This 4 year proposal is for 3 inter-related studies to l) examine the attributable risk of oral-genital contact for transmission of HlV (and factors associated that may increase the risk), 2) study initial replication events in vivo, at the level of the mucosal surface, among persons with recent sexual exposure to HIV, and 3) develop an ex vivo model of oral transmission using human oropharyngeal tissues and primary isolates of HIV. The 1st study will enroll serodiscordant couples into a prospective, longitudinal 24 month follow-up study. Couples will fill out weekly sex diaries and have regular standardized dental examinations and laboratory monitoring of blood and semen to determine factors that might affect risk of oral-genital contact for HIV transmission. Analysis will be centered on number of people seroconverting by oral contact, the per contact risk, viral load in blood and semen of the source partner, epidemiologic parameters (smoking, flossing, dental appliances, etc.), and dental condition of the recipient (peridontal indicies, salivary flow rate, and mucosal integrity). The 2nd study will focus on patients referred for post sexual exposure prophylaxis (PSEP). Subjects will undergo mucosal swab and biopsy to determine duration of infectious HIV on the mucosa and in situ hybridization and immunocytochemistry to determine which cell(s) are initially infected. The 3rd study will be to develop an ex vivo model of oral transmission to allow a more controlled exploration of potential mechanisms discovered in vivo. Studies will be done to determine which seminal cells are capable of harboring productive infection and which human oropharyngeal tissues can be infected from virus produced in the seminal cells.

用于评估无保护的口腔生殖器接触感染 HIV 的真实风险的数据有限。动物数据表明，扁桃体组织很容易感染 SIV，一些观察性研究表明，在与其他男性发生性行为的男性中，口腔传播率可能高达 20-25%。然而，没有数据可以估计异性口腔生殖器接触的风险。这项为期 4 年的提案涉及 3 项相互关联的研究，目的是 l) 检查口腔生殖器接触传播 HIV 的可归因风险（以及可能增加风险的相关因素），2) 研究体内的初始复制事件，水平3) 使用人类口咽组织和 HIV 初级分离株开发口腔传播的离体模型。第一项研究将招募血清不一致的夫妇参加一项前瞻性、纵向的 24 个月随访研究。夫妇将每周填写性日记，并定期进行标准化牙科检查以及血液和精液的实验室监测，以确定可能影响口腔生殖器接触艾滋病毒传播风险的因素。分析将集中于通过口腔接触而发生血清转化的人数、每次接触的风险、来源伴侣血液和精液中的病毒载量、流行病学参数（吸烟、使用牙线、牙科器具等）以及接受者的牙齿状况（牙周指标、唾液流量和粘膜完整性）。第二项研究将重点关注转诊接受性接触后预防 (PSEP) 的患者。受试者将接受粘膜拭子和活检以确定粘膜上感染性HIV的持续时间，并进行原位杂交和免疫细胞化学以确定哪些细胞最初被感染。第三项研究将开发一种口腔传播的离体模型，以便对体内发现的潜在机制进行更可控的探索。将进行研究以确定哪些精细胞能够携带生产性感染，以及哪些人类口咽组织可以被精细胞中产生的病毒感染。