Persistence of CNS T. pallidum in HIV infection

描述(申请人提供)：全世界每年有1200万人感染梅毒。大约三分之一的人居住在撒哈拉以南非洲，在那里，感染艾滋病毒的人感染梅毒的比例是没有感染的人的2-3倍。在美国，与所有一期和二期梅毒患者相比，感染艾滋病毒的患者的一期梅毒和二期梅毒的发病率高出80倍。早期神经梅毒在感染艾滋病毒的人中比在未感染艾滋病毒的人中更常见。早期神经梅毒会导致相当大的发病率，包括症状性脑膜炎、听力损失、眩晕和视力丧失。神经梅毒始于无症状脑膜炎。如果不治疗，无症状的神经梅毒可能会导致有症状的神经梅毒。对约25%的HIV感染者进行无症状神经梅毒的识别和治疗，将防止他们发展为有症状的疾病。然而，目前还没有敏感和具体的测试来识别这些人。解决这个问题的一种方法是对所有感染艾滋病毒的梅毒患者进行腰椎穿刺术。然而，这种方法在许多环境中是不切实际的，并且可能会浪费资源。在这项应用中，我们在556名HIV感染梅毒患者队列的基础上，开发和验证算法，以1)确定哪些HIV感染梅毒患者应该接受腰椎穿刺术，以及2)解释脑脊液异常。这些算法将使用一种名为分类和回归树(CART)分析的新统计方法来构建。此外，我们将确定伴随的抗逆转录病毒治疗，以及方案中特定抗逆转录病毒药物对神经梅毒治疗反应的影响。我们的研究是独一无二的。这是在艾滋病毒时代进行的唯一一项神经梅毒研究。神经梅毒在感染艾滋病毒的患者中具有显著的发病率。这项申请中提出的研究将为临床医生提供必要的工具，以最佳地评估、治疗和管理患有梅毒和神经梅毒的艾滋病毒感染患者。与公共卫生相关的梅毒，一种许多人认为或多或少已得到控制的疾病，正在发达国家卷土重来，并在发展中国家仍是地方病。许多感染者也感染了艾滋病毒，他们患一种名为神经梅毒的并发症的风险增加，这种并发症可能会在感染梅毒后的几周内导致失明、耳聋和中风。我们提议的研究建立在我们以前工作的基础上，并将导致更好地诊断和治疗神经梅毒的方法。

DESCRIPTION (provided by applicant): Throughout the world, 12 million people acquire syphilis every year. About one-third reside in sub-Saharan Africa, where the proportion of individuals with syphilis is 2-3 times higher in those who are HIV-infected compared to those who are not. In the US, compared to all patients with primary and secondary syphilis, rates of primary and secondary syphilis are 80 times higher in patients who are HIV-infected. Development of early neurosyphilis is more common in HIV-infected individuals than in those who are not HIV infected. Early neurosyphilis causes substantial morbidity, including symptomatic meningitis, hearing loss, vertigo, and visual loss. Neurosyphilis begins with asymptomatic meningitis. Untreated, asymptomatic neurosyphilis can lead to symptomatic neurosyphilis. Identification and treatment of the ~25% of HIV-infected patients with asymptomatic neurosyphilis would prevent them from progressing to symptomatic disease. However, there is currently no sensitive and specific test to identify these individuals. One approach to this problem would be to perform a lumbar puncture on all HIV-infected patients with syphilis. However this approach is impractical in many settings and potentially wastes resources. In this application, we build upon our previous work in a cohort of 556 HIV-infected subjects with syphilis to develop and validate algorithms to 1) determine which HIV- infected patients with syphilis should undergo lumbar puncture and 2) interpret CSF abnormalities. These algorithms will be constructed using a novel statistical method called classification and regression tree (CART) analysis. Further, we will determine the impact of concomitant antiretroviral therapy, and of particular antiretroviral agents within a regimen, on response to neurosyphilis therapy. Our study is unique. It is the only study of neurosyphilis conducted in the HIV era. Neurosyphilis carries significant morbidity in HIV-infected patients. The studies proposed in this application will yield the necessary tools for clinicians to optimally evaluate, treat and manage HIV-infected patients with syphilis and neurosyphilis. PUBLIC HEALTH RELEVANCE Syphilis, a disease that many thought was more or less controlled, is enjoying a major come back in the developed world and remains endemic in the developing world. Many of those infected also have HIV, and they are at increased risk of a complication called neurosyphilis, which can cause blindness, deafness and stroke within weeks after syphilis infection. Our proposed research builds on our previous work and will lead to ways to better diagnose and treat neurosyphilis.