HIV Incidence, Transmission Dynamics and Combination HIV Prevention: Rakai Uganda

描述（由申请人提供）：Rakai社区队列研究（RCCS）是一个开放队列研究，约15,800人，15-49人在乌干达Rakai农村的50个社区（艾滋病毒患病率约12.3%，发病率约1.0/100例）。使用基于伙伴关系的传播模型，我们估计每年40%的传播是由家庭外的伴侣引起的，其中约62%来自个人居住社区以外的已知伴侣（即，社区外接触将感染播撒到一般人群中）。这些感染的来源在很大程度上是未知的。2011- 2013年，监测范围扩大到关键社区，包括渔业社区（艾滋病毒患病率35-43%，发病率约3.9/100 py）和交通枢纽。在总统防治艾滋病紧急救援计划的支持下，该项目将在人口约40万的Rakai地区扩大艾滋病毒综合预防（CHP），包括抗逆转录病毒治疗、男性包皮环切、预防艾滋病毒母婴传播和创造需求/行为改变。我们将验证以下假设：1)重点社区将感染播撒到一般农村和重点社区人群中；2)卫生防护计划将通过改变农村和重点人群内部和之间的传播动态来降低艾滋病毒发病率。目标1将评估在扩大卫生防护计划规模之前（2011- 2013年）一般社区和重点社区内和社区之间的传播动态。性网络的空间规模将通过家庭GPS、伴侣位置和流动性进行评估。系统发育分析（gag和env的Sanger测序）将评估HIV传播的模式、时间和方向性。基于性伴侣和系统发育数据的传播建模将量化一般和关键社区内部和之间发生的传播比例。这解决了假设1，并为CHP影响评估提供了反事实。目标2将评估卫生防护中心服务扩大期间的艾滋病毒发病率和传播动态（2013- 2017年）。将监测卫生防护中心的覆盖情况。与社区卫生防护覆盖率和个人风险特征相关的人口水平艾滋病毒发病率风险比将量化卫生防护的影响。这项研究预计将使艾滋病毒发病率降低46%。传动动力学的变化将通过目标1的方法进行评估。结果将为非洲农村的卫生防护计划提供信息。

DESCRIPTION (provided by applicant): The Rakai Community Cohort Study (RCCS) is an open cohort of ~15,800 persons, 15-49 in 50 communities in rural Rakai, Uganda (HIV prevalence ~12.3%, incidence ~1.0/100 py.) Using partnership-based transmission models, we estimate that 40% of annual transmissions are due to extra-household partners of whom ~62% are from known partners outside an individual's community of residence (i.e., extra-community contacts seed infections into the general population.) The sources of these infections are largely unknown. In 2011-13, surveillance was extended to key communities including fishing communities (HIV prevalence 35-43%, incidence ~3.9/100 py) and transport hubs. With PEPFAR support, the Program will scale up combination HIV prevention (CHP) using antiretroviral therapy, male circumcision, prevention of mother-to-child HIV transmission and demand creation/behavioral modification in Rakai District (population ~400,000). We will test the hypotheses that: i) Key communities seed infection into the general RCCS population, and ii) that CHP will reduce HIV incidence through changing transmission dynamics within and between the general rural and key populations. Aim 1 will assess transmission dynamics in and between general and key communities prior to CHP scale-up (2011-13). The spatial scale of sexual networks will be assessed using household GPS, location of partners and mobility. Phylogenetic analyses (Sanger sequencing of gag and env) will assess patterns, timing and directionality of HIV transmission. Transmission modeling based on sexual partner and phylogenetic data will quantify the proportions of transmissions occurring within and between general and key communities. This addresses hypothesis 1, and provides the counterfactual for CHP Impact Evaluation. Aim 2 will assess HIV incidence and transmission dynamics during scale up of CHP services (2013-17.) CHP coverage will be monitored. The hazard ratio of population-level HIV incidence associated with community CHP coverage and individual risk characteristics will quantify the impact of CHP. The study is powered to detect an expected 46% reduction in HIV incidence. Changes in transmission dynamics will be assessed by the methods for Aim 1. Results will inform CHP programs in rural Africa.