Characterizing Extragenital Gonorrhea and Chlamydia: Natural History & HIV Impact

描述（由申请方提供）：在男男性行为者（MSM）中，咽部和直肠的淋病（GC）和衣原体（CT）感染占大多数。然而，由于主要是无症状感染，他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水库。由于淋病奈瑟氏菌的DNA结合能力和口咽部是淋病奈瑟氏菌的重要环境，咽部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获得艾滋病毒的风险。然而，我们对生殖器外GC和CT的自然史知之甚少，也不知道直肠GC/CT通过生物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和相关社会行为决定因素中生殖器外淋病和衣原体感染的自然史，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，他们将自行收集咽部和直肠拭子，并每周记录性活动，持续一年。我们将记录感染的发生率、持续时间和与生殖器外GC/CT相关的社会行为因素;我们将评估基线和偶发直肠感染之间HIV RNA对数拷贝的差异，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3）使用在城市STD诊所收集的10年以上的临床数据来测试HIV获得的风险是否与直肠GC或CT感染控制血清适应性行为相关;以及4）估计 使用确定性数学模型，增强生殖器外检测和治疗对GC、CT和HIV发病率的影响。这些研究不仅将回答关于生殖器外GC、CT和HIV的关键临床和流行病学问题，而且将提供体验式学习，以补充PI的结构化职业发展计划，从而培养纵向数据分析、社会行为研究和数学建模方面的技能。该K23奖项的最终目标是提供必要的时间，经验，培训和指导，使PI成为一名独立的调查员，致力于在弱势群体中预防和控制性病和艾滋病毒。

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.