EXPERIMENTAL HUMAN INFECTION WITH HAEMOPHILUS DUCREYI IN PERSONS WHO ARE HIV

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。杜克雷嗜血杆菌是一种引起软下疳的细菌，软下疳是一种在许多发展中国家很常见的生殖器溃疡病（GUD）。软下疳是一个公共卫生问题，因为患有软下疳的人获得人类免疫缺陷病毒（HIV）的速度高于没有软下疳的人。合并感染艾滋病毒和软下疳的人在其生殖器溃疡中可检测到艾滋病毒DNA或可恢复的艾滋病毒，并且可能比单独感染艾滋病毒的人更容易将艾滋病毒传播给其伴侣。然而，关于细菌感染如何影响合并感染患者的HIV复制，人们知之甚少。本方案的目的是评价用H. ducreyi和研究H. ducreyi与艾滋病毒相互作用。我们的假设是，局部感染H。ducreyi治疗疾病的脓疱期将是安全的，并且不会影响病毒复制或系统区室中的CD 4计数，但会将潜伏感染的记忆CD 4细胞和巨噬细胞募集到病变中，激活它们，并使它们局部产生病毒。这些研究将帮助我们了解使合并感染者比单独感染HIV的人更有效传播HIV的生物学机制，确定哪些潜伏感染细胞在免疫刺激下产生HIV，并提供令人信服的科学依据，将公共卫生工作重点放在HIV流行地区的软下疳根除上。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Haemophilus ducreyi is a bacterium that causes chancroid, a genital ulcer disease (GUD) that is common in many developing countries. Chancroid is a public health problem because persons with chancroid acquire the human immunodeficiency virus (HIV) at a rate that is higher than persons who do not have chancroid. Persons who are co-infected with HIV and chancroid have detectable HIV DNA or recoverable HIV in their genital ulcers and may transmit HIV more readily to their partners than persons infected with HIV alone. However, little is known about how the bacterial infection affects HIV replication in co-infected patients. The purpose of this protocol is to evaluate the safety of infecting selected, clinically stable, HIV seropositive individuals with H. ducreyi and to examine how H. ducreyi interacts with HIV. Our hypotheses are that local infection with H. ducreyi to the pustular stage of disease will be safe, and will not affect viral replication or CD4 counts in the systemic compartment, but will recruit latently infected memory CD4 cells and macrophages into the lesions, activate them, and cause them to produce virus locally. These studies will help us understand the biological mechanisms that allow co-infected persons to be more efficient transmitters of HIV than persons infected with HIV alone, establish which latently infected cells produce HIV upon immune stimulation, and provide a compelling scientific rationale to focus public health efforts on chancroid eradication in HIV endemic areas.