Determining Whether Transient HIV Infection Occurs

确定是否发生暂时性 HIV 感染

• 批准号: 7064570
• 负责人: Miles W. Cloyd
• 金额: $ 37.75万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-04 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7064570
• 关键词: HIV infections; clinical research; disease /therapy duration; epidemiology; high risk behavior /lifestyle; human subject; longitudinal human study; lymphocyte; polymerase chain reaction; tissue /cell culture

DESCRIPTION (provided by applicant): We have both old and more recent data which indicate that adults at high risk for HIV infection may sometimes become transiently infected with HIV. This includes: (1) transient appearance of serum antibodies (Ab) to conformational epitopes to gp41/gp160; (2) transient appearance of HIV in the PBMCs at the same time as Ab in some of the cases; (3) paternity typing of PBMC samples taken at the time of Ab and virus positivity, and later, when the subject is negative for both, thereby showing that they are from the same subject; (4) sequence analysis of the viruses present in transiently infected subjects, showing that they are not lab contaminants; and (5) demonstration in one case in which the virus in a transiently infected subject was genetically related to the virus in genital fluids from his HIV+ partner. Longitudinal statistics from studies of 37 high-risk subjects over 4 years showed that putative transient infections were more frequent than progressive infections and that the former was associated with unprotected oral sex, while the later was associated with unprotected genital sex. HIV was found by PCR in the tonsil of one such transiently HIV infected subject, but it was not detected in the PBMCs. We hypothesize that transient HIV infections do occur in high-risk adults, and we will focus this project only on proving or disproving this hypothesis. Our specific aims iare 1) to longitudinally screen at every 2-3 months 300 high-risk subjects for serological evidence of HIV infection; (2) attempt to detect HIV in the Ab-positive subjects and their source partners by nested PCR and PBMC culture; (3) sequence env and nef genes that are amplified and perform phylogenetic analyses to show relatedness between viruses in putative transiently infected subjects and their source partners; and (4) demonstrate that blood samples have not been mixed up. Although transient infection is presently controversial, our data indicate that it occurs and we will attempt to prove it.

描述（由申请人提供）：我们有旧的和最近的数据表明，艾滋病毒感染高风险的成年人有时可能会短暂感染艾滋病毒。这包括：(1)针对gp41/gp160构象表位的血清抗体（Ab）的短暂出现；(2)部分病例的PBMCs中HIV与Ab同时短暂出现；(3)在抗体和病毒呈阳性时以及在抗体和病毒均呈阴性时采集的PBMC样本的父系分型，从而表明它们来自同一受试者；(4)对暂时感染对象体内存在的病毒进行序列分析，表明它们不是实验室污染物；(5)在一宗个案中，证明暂时受感染的对象所携带的病毒与其艾滋病毒阳性伴侣所携带的生殖器分泌液中的病毒有基因上的关系。对37名高风险受试者4年的纵向统计表明，假定的短暂性感染比进行性感染更频繁，前者与无保护的口交有关，后者与无保护的生殖器性交有关。用PCR方法在一名短暂性HIV感染者的扁桃体中发现了HIV，但在PBMCs中未检测到。我们假设短暂的HIV感染确实发生在高风险的成年人中，我们将只关注这个项目来证明或反驳这个假设。我们的具体目标是：1)每2-3个月对300名高危受试者进行纵向筛查，寻找HIV感染的血清学证据；(2)尝试通过巢式PCR和PBMC培养检测ab阳性受试者及其源性伴侣的HIV；(3)对扩增的env和nef基因进行测序，并进行系统发育分析，以显示假定的暂时感染受试者的病毒与其源伴侣之间的相关性；(4)证明血液样本没有混淆。虽然暂时感染目前存在争议，但我们的数据表明它确实存在，我们将试图证明它。