Enhanced STI management to reduce genital inflammation and HIV risk

 描述(由申请人提供)：性传播感染(STI)与艾滋病毒风险密切相关。然而，以人群为基础的研究将性传播感染作为降低艾滋病毒风险的一种方式进行管理，但收效甚微。最近的研究表明，生殖道炎性细胞因子的升高与艾滋病毒感染风险的增加密切相关，而性传播感染是生殖道细胞因子升高的最常见原因之一。对细胞因子在艾滋病毒感染中的作用的兴趣重新激起了对性传播感染的兴趣，以及更好的管理战略是否可以在减少艾滋病毒风险方面发挥作用。艾滋病毒和性传播疾病在南非夸祖鲁-纳塔尔省(KZN)极为常见，该省的性传播感染诊断和治疗面临许多挑战，包括依赖症状管理、基于对性传播感染综合征(阴道分泌物、尿路分泌物和生殖器溃疡)的认识采取的方法，然后针对该综合征的常见原因进行治疗。这种方法对检测性传播感染的敏感度和特异度较低，80%-85%没有得到诊断和治疗。当前STI管理面临的其他挑战包括有限合伙人通知和治疗。在人口层面上，结果是大多数性传播感染仍未得到治疗，社区内的性传播感染负担仍未得到控制。我们的目标是确定创新的、增强的STI管理计划是否会导致更高的治愈率和更低的复发率，从而减少生殖器炎性细胞因子，从而降低HIV风险。这项概念验证研究将通过使用一种创新的医疗保健点诊断测试(一种用于同时检测淋球菌和沙眼衣原体的自动化、盒式核酸扩增分析(GeneXpert))来确认性传播感染患者。这项技术最近在南非各地大规模推广，以检测结核病和结核病耐药性，从而加快诊断和治疗，并加强控制结核病的公共卫生倡议。然后，我们将使用Bio-Plex Pro人类细胞因子试剂盒和Bio-Plex MAGPIX阵列读取器测量48种生殖道细胞因子。然后，我们将在直接监督下立即对他们进行适当的治疗，为参与者提供相同的治疗，以便将他们的性伴侣带回家(快速伴侣治疗)，并要求他们在6周和3个月后返回进行治愈测试。然后，我们将测试参与者的生殖道炎性细胞因子，并确定这些细胞因子是否有所减少。总体而言，我们针对STI护理的创新增强管理方案，通过确保个体治愈并降低再次感染风险，提供了减少STI的最佳机会 伴侣疗法。这将使我们能够确定在有效的性传播感染治疗后是否可以减少生殖器炎症，并最终降低南非和美国感染艾滋病毒的风险。

 DESCRIPTION (provided by applicant): Sexually transmitted infections (STIs) are strongly associated with HIV risk. However, population based studies to manage STIs as a way of reducing HIV risk have had limited success. Recent studies show that elevated genital tract inflammatory cytokines are strongly associated with an increased risk of HIV acquisition, and STIs are one of the commonest causes of elevated genital tract cytokines. This interest in the role of cytokines in HIV acquisition has reinvigorated interest in STIs and whether better management strategies can have a role in HIV risk reduction. HIV and STIs extremely common in the South African province of KwaZulu-Natal (KZN) where there are many challenges with STI diagnosis and treatment, including the reliance on syndromic management, an approach based on the recognition of STI syndromes (vaginal discharge, urethral discharge and genital ulceration), followed by treatment targeting the common causes of the syndrome. This approach has a low sensitivity and specificity for detecting STIs, leaving 80-85% undiagnosed and untreated. Other challenges with current STI management include limited partner notification and treatment. At a population level, the result is that most STIs remain untreated and the burden of STIs within the community remains unchecked. Our goal is to determine if an innovative, enhanced program of STI management will result in a higher cure rate and a lower recurrence rate, with a subsequent reduction in genital inflammatory cytokines and hence HIV risk. This proof of concept study will be addressed by identifying individuals with STIs using an innovative, point-of-care diagnostic test (an automated, cartridge-based nucleic amplification assay (GeneXpert) for the simultaneous detection of N. gonorrhoeae and C. trachomatis. This technology has recently been introduced on a large scale across South Africa to detect tuberculosis (TB) and TB drug resistance, thereby accelerating diagnosis, treatment and enhancing public health initiatives to control TB. We will then measure 48 genital tract cytokines using Bio-Plex Pro Human Cytokine kits and a Bio-Plex MagPix Array Reader. We will then treat them immediately with appropriate therapy under direct supervision, giving the participants the same treatment to take home for their sexual partners (expedited partner therapy) and asking them to return after 6 weeks and 3 months for a test of cure. We will then test participants for genital tract inflammatory cytokines and determine if these have decreased. Overall, our innovative enhanced management package for STI care, offers the best opportunity to reduce STIs, by ensuring that the individual is cured and reducing the risk of reinfection using expedited partner therapy. This will allow us to determine whether genital inflammation can be reduced after effective STI treatment, and ultimately reduce the risk of HIV acquisition in SA and also in the USA.