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，处于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gp 41/gp 160的构象表位的血清抗体（Ab）的瞬时出现;（2）在某些情况下，HIV与Ab同时在PBMC中瞬时出现;（3）在Ab和病毒阳性时以及之后当受试者对两者均为阴性时采集的PBMC样品的亲子鉴定分型，从而表明它们来自同一受试者;（4）对短暂感染受试者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）在一例病例中证明，短暂感染受试者体内的病毒与其HIV+伴侣生殖器液中的病毒在遗传上相关。对37名高危受试者进行的4年以上研究的纵向统计显示，推定的一过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交有关。通过PCR在一个这样的瞬时HIV感染受试者的扁桃体中发现HIV，但在PBMC中未检测到HIV。我们假设短暂的HIV感染确实发生在高危成人中，我们将把这个项目的重点放在证明或反驳这一假设上。我们的具体目标是：（1）每2-3个月对300例高危人群进行一次HIV感染的血清学筛查：（2）尝试用巢式PCR和PBMC培养法检测Ab阳性者及其源伴中的HIV;（三）对扩增的env和nef基因进行测序，并进行系统发育分析，以显示推定的短暂感染受试者中的病毒与其来源伙伴;以及（4）证明血液样本没有被混合。虽然暂时性感染目前是有争议的，我们的数据表明，它发生，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.