Characterizing Extragenital Gonorrhea and Chlamydia: Natural History & HIV Impact

描述（由申请人提供）：淋病（GC）和衣原体（CT）在咽和直肠构成了大多数的GC和CT感染的男性与男性发生性关系（MSM）。然而，作为主要的无症状感染，它们往往得不到诊断和治疗。因此，这些生殖器外部位的GC/CT感染可能构成MSM人群中持续传播的重要储存库。由于淋病奈瑟菌独特的DNA清除能力和口咽部作为共生奈瑟菌物种的重要环境，咽部的淋球菌感染也可能在促进抗菌素耐药性的发展中发挥重要作用。直肠GC/CT感染已被证明会增加感染艾滋病毒的风险。然而，关于生殖器外GC和CT的自然历史知之甚少，也不知道直肠GC/CT通过生物学介导的过程或性行为增加HIV感染风险的程度。这项K23提案旨在1)确定MSM中生殖器外淋病和衣原体感染的自然史及相关的社会行为决定因素，2)通过对MSM进行前瞻性队列研究，量化直肠GC/CT感染期间直肠HIV脱落的变化，其中一半是HIV感染者，他们将每周收集咽和直肠拭子并记录一年的性活动。我们将通过外生殖器GC/CT记录感染的发生率、持续时间和相关的社会行为因素；我们将评估基线和直肠感染事件之间HIV RNA日志拷贝的差异，并描述直肠GC/CT感染过程中HIV RNA脱落的时间变化。我们还将使用在城市性病诊所收集的超过10年的临床数据来测试HIV感染风险是否与控制血清适应行为的直肠GC或CT感染有关；4)评估潜在的影响

DESCRIPTION (provided by applicant): Gonorrhea (GC) and chlamydia (CT) at the pharynx and the rectum comprise the majority of GC and CT infections in men who have sex with men (MSM). However, as primarily asymptomatic infections, they often go undiagnosed and untreated. As such, GC/CT infections at these extra-genital sites may constitute an important reservoir of sustained transmission in the MSM population. Gonococcal infections at the pharynx may also play an important role in fostering the development of antimicrobial resistance due to the unique constellation of Neisseria gonorrhoeae's ability to scavenge DNA and the oropharynx as important environment for commensal Neisseria species. Rectal GC/CT infections have been shown to increase the risk for HIV acquisition. However, little is known about the natural history of extra-genital GC and CT, nor the extent to which rectal GC/CT increase the risk of HIV acquisition through a biologically-mediated process or sexual behavior. This K23 proposal aims to 1) determine the natural history extra-genital gonorrhea and chlamydia infection among MSM & associated sociobehavioral determinants, and 2) quantify variations in HIV shedding at the rectum during rectal GC/CT infection by conducting a prospective cohort study of MSM, half of which are HIV-infected, who will self-collect pharyngeal and rectal swabs and document sexual activity on a weekly basis for one year. We will document incidence, duration of infection, and associated sociobehavioral factors with extra-genital GC/CT; and we will evaluate differences in HIV RNA log copies between baseline and incident rectal infections as well as describe temporal variations in HIV RNA shedding over the course of rectal GC/CT infections. We will also 3) test whether the risk of HIV acquisition is associated with rectal GC or CT infection controlling for seroadaptive behaviors using more than 10 years of clinical data collected at an urban STD Clinic; and 4) estimate the potential impact of enhanced extra-genital testing and treating on the incidence of GC, CT and HIV using deterministic mathematical modeling. Not only will these studies answer key clinical and epidemiologic question about extra-genital GC, CT and HIV, but these studies will provide experiential learning to complement a structured career development plan for the PI to develop skills in longitudinal data analysis, sociobehavioral research and mathematical modeling. The ultimate goal of this K23 award is to provide the time, experience, training and mentorship necessary to allow the PI to become an independent investigator dedicated to the prevention and control of STD and HIV in vulnerable populations.