Determining Whether Transient HIV Infection Occurs

描述(由申请人提供)：我们有旧的和最近的数据表明，艾滋病毒感染的高危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)的瞬时出现；(2)在某些情况下，HIV在PBMC中与Ab同时出现；(3)在抗体和病毒阳性时，以及后来当受试者两者均为阴性时，采集的PBMC样本的亲子鉴定，从而表明它们来自同一受试者；(4)对瞬时感染受试者中存在的病毒进行序列分析，表明它们不是实验室污染物；以及(5)在一例病例中，瞬时感染对象体内的病毒与其HIV+性伴侣生殖液中的病毒存在遗传关系。对37名高危人群4年来的纵向研究统计表明，暂时性感染比进行性感染更常见，前者与无保护的口交有关，而后者与无保护的生殖器性行为有关。通过聚合酶链式反应在一名这样的暂时性HIV感染者的扁桃体中发现了HIV，但在PBMC中没有检测到它。我们假设短暂的HIV感染确实发生在高危成年人中，我们将只专注于证明或反驳这一假设。我们的具体目标是：1)每隔2-3个月对300名高危受试者进行艾滋病毒感染血清学证据的纵向筛查；(2)尝试通过套式聚合酶链式反应和PBMC培养在抗体阳性受试者及其来源伙伴中检测艾滋病毒；(3)扩增env和nef基因序列，并进行系统发育分析，以显示假定的瞬时感染受试者及其来源伙伴中的病毒之间的关系；以及(4)证明血液样本没有混淆。尽管暂时性感染目前存在争议，但我们的数据表明它确实发生了，我们将试图证明这一点。

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.