A Multisectoral Strategy to Address Persistent Drivers of the HIV Epidemic in East Africa

项目摘要 消除艾滋病毒的进展将停滞不前，除非我们通过以下措施克服新的艾滋病毒感染的持续驱动因素： 联合优化艾滋病毒治疗和有效提供艾滋病毒预防模式。我们的目标是确定 利用艾滋病毒预防和治疗的创新战略，将艾滋病毒发病率降至<0.1%，同时 通过分两个阶段优化和评估的可扩展干预措施，接触“持久驱动因素”人群。 ·在A期（1-2年），我们将进行个体随机对照试验（RCT），以优化 以下预防和治疗包：1）动态选择艾滋病毒预防与灵活的预 将接触/接触后预防纳入计划生育、产前护理和 艾滋病毒诊所和社区青年中心也提供生活技能， 小额信贷和职业培训。2)动态选择艾滋病毒治疗与个人和系统护理 为年轻人、男性、移动的人群和酗酒者量身定制的选择和服务。 ·在阶段B（3-5年），我们将测试多部门干预的假设，提供动态选择 针对持续驾驶人群的生物医学艾滋病毒预防和治疗将增加病毒抑制 艾滋病毒感染率的下降幅度大于标准护理。 目标1：优化动态预防和治疗干预措施：我们将进行PrEP/PEP的随机对照试验 在高危人群的多个场所进行动态预防， 病毒载量未受抑制的多个人群。主要疗效结局（艾滋病毒预防覆盖率和 病毒抑制）将与实施成果、成本计算、建模预测和利益相关者一起使用 为优化B阶段的动态预防和治疗干预措施提供投入。 目的2：a）比较动态选择预防和动态选择治疗的效果 干预措施与标准护理在预防覆盖率、病毒抑制、艾滋病毒发病率和 3年的社区健康状况。我们将使用社区随机2x2析因设计来确定 每一套干预措施及其组合对预防覆盖率、病毒抑制等的影响 健康成果。B）通过评价执行情况阐明干预措施的影响途径， 过程结果和社会行为途径的行动在社区，诊所和个人层面。 目标3：确定可持续性并为政策提供信息。我们将对每个方面进行多站点成本计算， 多组成部分干预措施和估计避免艾滋病毒感染的成本以及对多种疾病的影响 残疾调整生命年（Disability-adjusted life-years，DIFE）。将利用纳入研究数据的建模向利益攸关方提供信息 替代性预防和治疗战略的预期长期健康影响和成本。 意义：这项研究将解决有关如何克服助长艾滋病毒的关键因素的主要知识差距 这一流行病为利益攸关方提供了信息，并指导了加快消除艾滋病毒的政策。

Project Summary Progress towards HIV elimination will stall unless we overcome persistent drivers of new HIV infections by jointly optimizing HIV treatment and effectively delivering HIV prevention modalities. We aim to determine how to reduce HIV incidence to <0.1% using innovative strategies for HIV prevention and treatment to concurrently reach “persistent driver” populations with scalable interventions optimized and evaluated in two phases. • In Phase A (years 1-2), we will conduct individually randomized controlled trials (RCTs) to optimize the following prevention and treatment packages: 1) Dynamic Choice HIV Prevention with flexible Pre- exposure/post-exposure prophylaxis (PrEP/PEP) access integrated at family planning, antenatal care and HIV clinics and at community Youth Hubs that generate demand by also offering provision of life-skills, micro-finance and vocational training. 2) Dynamic Choice HIV Treatment with individual and system care options and services tailored for youth, men, mobile populations, and heavy drinkers. • In Phase B (years 3-5), we will test the hypothesis that a multi-sector intervention, offering dynamic choice of biomedical HIV prevention and treatment for persistent driver populations will increase viral suppression and prevention coverage and lead to a reduction in HIV incidence greater than standard of care. Aim 1: Optimize dynamic prevention and treatment interventions: We will conduct RCTs of PrEP/PEP dynamic prevention at multiple venues with high risk populations, and dynamic treatment interventions for multiple populations with unsuppressed viral load. Primary efficacy outcomes (HIV prevention coverage and viral suppression) will be used with implementation outcomes, costing, modelling projections, and stakeholder input to optimize dynamic prevention and treatment intervention packages for Phase B. Aim 2: a) Compare the effect of Dynamic Choice Prevention and Dynamic Choice Treatment interventions vs. standard-of-care on prevention coverage, viral suppression, HIV incidence and community health outcomes at 3 years. We will use a community randomized 2x2 factorial design to identify effect of each intervention package and their combination on prevention coverage, viral suppression, and other health outcomes. b) Elucidate pathways of intervention impact via evaluation of implementation and process outcomes and of socio-behavioral pathways of action at the community, clinic, and individual levels. Aim 3: Determine sustainability and inform policy. We will conduct multi-site costing of each aspect of the multi-component intervention and estimate costs per HIV infection averted and impacts on multi-disease disability-adjusted life-years (DALYs). Modelling incorporating study data will be used to inform stakeholders on anticipated long-term health impact and costs of alternative prevention and treatment strategies. Significance: This study will address major knowledge gaps on how to overcome key factors fueling the HIV epidemic that inform stakeholders and guide policies towards accelerating the path to HIV elimination.