Identifying sources of HIV infection in adolescent girls in rural South Africa

 南非的少女仍然不成比例地受到艾滋病毒流行病的影响，尽管有几种行为干预措施可以减少艾滋病毒的性传播。更好地了解导致少女艾滋病毒传播的性网络，将大大有助于减少这一关键人群中艾滋病毒传播的战略。此外，如果青春期女孩的艾滋病毒感染率 这可能会打破关键的传播链，减少艾滋病毒在普通人群中的传播。我们假设，复杂的性网络，包括青少年和社区成员之间的混合，推动南非农村少女艾滋病毒的高发病率。为了验证我们的假设，我们将利用一种创新的方法来识别HIV传播网络，该方法将联合收割机广泛的流行病学采样与HIV-1序列数据的系统发育分析和传统的性网络方法相结合。系统发育分析最近成为利用病毒多样性来研究受影响人群中HIV-1传播的潜在动态的最有力和最翔实的方法之一。然而，这些方法往往未能发现在地方性环境中的联系，这可能是由于代表性不足，因为稀疏的抽样传播对在大量的艾滋病毒感染者的个人。该提案的主要创新之一是确定青少年中的HIV-1簇和病毒联系，并通过从确定的地理区域（夸祖鲁-纳塔尔的Vulindlela分区的一部分）广泛抽样艾滋病毒感染者，将其与社区序列联系起来，使用几种流行病学方法实现人口覆盖率的“饱和”。这一地区是唯一适合这项研究的研究领域是农村和地理上明确界定;这是在南非和CAPRISA艾滋病毒负担最高的地区之一，收集了详细的数据，在过去十年中，在这个社区的艾滋病毒感染的风险的结构，行为和生物决定因素。基于我们在这一领域的艾滋病毒监测专业知识，我们将：i）通过结合新的招募策略，包括基于诊所和学校的招募，以及针对难以接触的人群的响应者驱动的采样，提高系统发育分析的代表性; ii）使用高通量测序和生物信息学来确定通过HIV-1病毒链接的HIV-1传播网络;包括行为和生物信息以及其他风险因素。这种方法将使我们能够描述这个高度流行地区的艾滋病毒传播集群和病毒联系，分析艾滋病毒集群对少女中新感染的贡献，并利用这些数据来改善这一关键人群的艾滋病毒预防工作，以控制艾滋病毒。

 DESCRIPTION (provided by applicant Adolescent girls in South Africa remain disproportionately affected by the HIV epidemic, despite the availability of several behavioural interventions to reduce the sexual transmission of HIV. Strategies to reduce HIV transmission in this key population would benefit greatly from a better understanding of the sexual networks that drive HIV transmission in adolescent girls. Furthermore, if HIV infection rates in adolescent girls can be reduced, this could break critical chains of transmission and decrease the spread of HIV in the general population. We hypothesise that complex sexual networks, including mixing between adolescents and community members, drive high HIV incidence in adolescent girls in rural South Africa. To test our hypothesis we will utilize an innovative approach to identify networks of HIV transmission that combine extensive epidemiologic sampling with phylogenetic analyses of HIV-1 sequence data and traditional sexual networking methods. Phylogenetic analysis has recently emerged as one of the most powerful and informative ways to use viral diversity to examine the underlying dynamics of HIV-1 transmission in affected populations. However, these methods have often failed to find linkages in endemic settings; this is likely due to underrepresentation because of sparse sampling of transmission pairs in large populations of HIV infected individuals. One of the major innovations of this proposal is identifying HIV-1 clusters and viral linkages in adolescents and link these to community sequences by extensively sampling HIV infected individuals from a defined geographic area (part of the sub-district of Vulindlela in KwaZulu-Natal), using several epidemiologic approaches to achieve a 'saturating' rate of population coverage. This area is uniquely suited for this research as the study area is rural and geographically well defined; it is one of the highest HIV burden districts in South Afric and CAPRISA has collected detailed data on the structural, behavioural and biological determinants of risks of HIV infection in this community over the last decade. Building on our expertise in HIV surveillance in this area we will i) enhance the representativeness of the phylogenetic analyses by combining novel recruitment strategies including clinic- and school-based recruitment, and respondent-driven sampling for hard-to-reach populations; ii) use high- throughput sequencing, and bioinformatics to identify HIV-1 transmission networks through HIV-1 viral linkages; and iii) include behavioural and biological information and other risk factors. This approach will allow us to characterize HIV transmission clusters and viral linkages in this hyper endemic region, analyze the contribution of HIV clusters to the new infections occurring among adolescent girls, and use this data to improve HIV prevention efforts in this key population for HIV control.