Multi-component, Targeted HIV Prevention for sub-Saharan Africa: PreventionRx

描述(由申请人提供)： 摘要：撒哈拉以南非洲普遍存在的艾滋病毒流行的特点是人口流行率高，对艾滋病毒血清状态的了解较低，大多数艾滋病毒传播发生在稳定的异性伴侣关系中。任何单一的艾滋病毒预防战略都不能控制非洲的艾滋病毒疫情；因此，需要多层次、多组成部分的预防。我们建议开发一套协调的、多组成部分的艾滋病毒预防方案，包括基于证据的生物医学和行为干预措施，这些措施将是个性化的，并有针对性地最大限度地扩大覆盖范围，最大限度地影响非洲人口的艾滋病毒发病率。将通过一个以社区为基础的以家庭为基础的自愿自愿接种(HBCT)平台提供这一方案，以加强人口一级的覆盖面和对血清状态的了解，同时在社区一级提供关键的预防信息。在东非，HBCT已被证明是可行的、可接受的和具有成本效益的，并提供了一种独特的适当机制来识别不知道自己感染艾滋病毒的人、艾滋病毒不和谐的夫妇和未感染艾滋病毒的高危人群--这些人是以艾滋病毒预防为目标的高优先人群。我们假设，使用HBCT平台，将适当的生物医学和行为干预结合起来，在普遍的非洲异性恋流行中协同减少人群水平的艾滋病毒传播，向高覆盖率的关键亚群提供个性化的“艾滋病毒预防处方”是可行和可接受的。我们的具体目标是：1.进行流行病学分析、系统评价和数学建模，以确定撒哈拉以南非洲人口归因率最高的异性恋艾滋病毒传播的可改变决定因素，评估针对这些决定因素的有针对性的预防战略的影响，并根据这些分析选择预防一揽子计划的组成部分。2.通过将行为和生物医学预防干预措施纳入以人口为基础的HBCT方案并以此为目标，试点收集数据，以确定最高风险个人(艾滋病毒不和谐的夫妇、艾滋病毒感染者和具有高危行为的艾滋病毒阴性者)。3.在HBCT的背景下，为东非和南部非洲设计一项全面的、有针对性的、生物医学和行为方面的艾滋病毒预防一揽子计划的社区随机有效性试验。我们的多学科团队包括流行病学家、数学模型师、生物统计学家和在非洲进行多中心生物医学和行为干预试验方面拥有广泛专业知识的调查人员。我们建议HBCT作为一个平台，提供社区范围的艾滋病毒风险行为评估，并向高危个人提供个性化的、多成分的生物医学(例如，男性包皮环切术、ART)和行为艾滋病毒预防方案。这一有针对性的“预防处方”将成为这一应用程序产品的基础：一种未来针对撒哈拉以南非洲普遍的异性恋流行病的多组分艾滋病毒预防一揽子社区随机试验的设计和方案。基于对非洲普遍的异性恋流行中艾滋病毒传播决定因素的流行病学分析和数学建模以及潜在的干预措施，我们将设计一套循证艾滋病毒预防方案和这一预防方案的社区随机试验，并将在以家庭为基础的自愿艾滋病毒咨询和检测平台上实施，以针对高危人群，实现高水平的覆盖。

DESCRIPTION (provided by applicant): Abstract: The generalized HIV epidemics in sub-Saharan Africa are characterized by high population prevalence, low knowledge of HIV serostatus, and the majority of HIV transmissions occurring within stable heterosexual partnerships. No single HIV prevention strategy will control the African HIV epidemic; thus, multi-layered and multi-component prevention will be needed. We propose to develop a coordinated, multi-component HIV prevention package of evidence-based biomedical and behavioral interventions that will be individually-tailored and targeted to maximize coverage and impact on HIV incidence in an African population. The package will be delivered through a community-based platform of household-based VCT (HBCT) to enhance population-level coverage and knowledge of serostatus, coupled to community-level delivery of key prevention messages. HBCT has been demonstrated to be feasible, acceptable and cost-effective in East Africa and provides a uniquely suitable mechanism to identify persons unaware of their HIV infection, HIV discordant couples, and high-risk HIV uninfected persons - high priority populations for targeting HIV prevention. We hypothesize that, using a HBCT platform, it is feasible and acceptable to deliver an individualized "HIV prevention prescription" to critical subpopulations with high levels of coverage, combining appropriate biomedical and behavioral interventions that are likely to synergistically reduce population-level HIV transmission in the generalized African heterosexual epidemic. Our Specific Aims are to: 1. Conduct epidemiologic analyses, systematic reviews, and mathematical modeling to identify modifiable determinants of heterosexual HIV transmission with the highest population-attributable fraction in sub-Saharan Africa, estimate the impact of targeted prevention strategies directed at these determinants, and select components of a prevention package based on these analyses. 2. Pilot data collection for identification of highest-risk individuals (HIV discordant couples, HIV-infected persons, and HIV-negative persons with high-risk behaviors) with integration and targeting of behavioral and biomedical prevention interventions into population-based HBCT programs. 3. Design a community-randomized effectiveness trial of a comprehensive, targeted, biomedical and behavioral HIV prevention package for East and southern Africa in the context of HBCT. Our multi-disciplinary team includes epidemiologists, mathematical modelers, biostatisticians, and investigators with extensive expertise in conducting multi-center biomedical and behavioral intervention trials in Africa. We propose HBCT as a platform to deliver community-wide behavioral assessment of HIV risk and to provide individualized, multi-component biomedical (e.g., male circumcision, ART) and behavioral HIV prevention packages to at-risk individuals. This targeted "prevention prescription" will be the foundation for the product of this application: a design and protocol for a future community-randomized trial of a multi-component HIV prevention package for the generalized heterosexual epidemics in sub-Saharan Africa. Based on epidemiologic analyses and mathematical modeling of HIV transmission determinants in generalized heterosexual epidemics in Africa and potential interventions, we will design an evidence-based HIV prevention package and a community-randomized trial of this prevention package which will be implemented on a platform of home-based voluntary HIV counseling and testing to target high-risk persons and achieve high levels of coverage.