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）是一项开放队列研究，约有15，800人，15-49人，分布在乌干达Rakai农村的50个社区（HIV患病率约为12.3%，发病率约为1.0/100 py）。使用基于伴侣的传播模型，我们估计40%的年度传播是由于家庭外伴侣，其中约62%来自个人居住社区以外的已知伴侣（即，社区外接触者将种子感染到普通人群中。这些感染的来源在很大程度上是未知的。2011- 2013年，监测范围扩大到主要社区，包括渔业社区（艾滋病毒流行率为35- 43%，发病率约为3.9/100 py）和交通枢纽。在总统艾滋病紧急救援计划的支持下，该方案将在Rakai县（人口约40万）利用抗逆转录病毒疗法、男性包皮环切术、预防艾滋病毒母婴传播和创造需求/改变行为来扩大艾滋病毒综合预防。我们将检验以下假设：i）主要社区将感染种子传播到一般RCCS人群中，以及ii）CHP将通过改变一般农村和主要人群内部和之间的传播动态来降低HIV发病率。目标1将在扩大卫生防护中心规模（2011- 2013年）之前，评估一般社区和主要社区内部及其之间的传播动态。性网络的空间规模将使用家庭全球定位系统、伴侣的位置和流动性进行评估。系统发生分析（gag和env的桑格测序）将评估HIV传播的模式、时间和方向。基于性伴侣和系统发育数据的传播模型将量化一般社区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扩大服务期间（2013-17年）的艾滋病毒发病率和传播动态。卫生防护中心的覆盖率将受到监测。与社区卫生防护中心覆盖率和个人风险特征相关的人口水平艾滋病毒发病率的风险比将量化卫生防护中心的影响。这项研究有能力检测到艾滋病毒发病率预期下降46%。传输动态的变化将通过目标1的方法进行评估。研究结果将为非洲农村的CHP项目提供信息。

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.