Stress and HIV infection in South African adolescent girls.

项目摘要/摘要 在撒哈拉以南非洲，少女和年轻妇女感染艾滋病毒的风险仍然很高 而这种增加的风险与社会和人际因素有关。对中低收入人群的研究很少 各国已经收集了压力反应生物标记物来了解生物过程，例如 生理应激反应，这可能是在AGYW中观察到的艾滋病毒感染风险增加的原因。 越来越多的证据表明，健康的社会决定因素与生理效应之间存在关联 美国和欧洲的压力很大，但撒哈拉以南的非洲缺乏这种压力。压力已经被认为是 与健康的社会决定因素和艾滋病毒携带者的不良后果；然而，这些研究 调查对象为成年人，样本量小，有关艾滋病毒感染事件的证据有限。这个 拟议项目的首要目标是产生初步证据，审查 心理社会应激源、生物应激与艾滋病预防、护理和治疗之间的关系 在南非的AGYW。项目目标将通过三个具体目标来实现：使用现有的和 独特的数据来源(艾滋病毒预防试验网络068研究)，提供有关心理社会应激源的信息， 应激反应生物标记物和2,533个AGYW队列中的HIV发病率 在南非的9年时间里，在目标1中，我们将评估急性(身体和性)亲密之间的联系 伴侣暴力、创伤性事件)和慢性(食品不安全、抑郁和父母支持不足) 应激反应免疫生物标记物(C-反应蛋白[CRP]效价，疱疹)的心理社会应激源 AGYW中单纯疱疹病毒1型(HSV-1)滴度较高，巨细胞病毒(CMV)滴度较高。我们将使用1,517个数据 AGYW在2018/19年的访问中提供了生物标记物信息，并将探索艾滋病毒对效果的修改 状态以及与感知到的压力的相关性。在目标2中，我们将对849名妇女进行一项病例队列研究，以 评估青春期应激反应生物标志物与性行为的关系 并在以后的时间点发生艾滋病毒感染事件。我们将对现有的、储存的生物样本进行回溯性测试 病例和对照，以评估这些关系。在目标3中，我们将评估压力与 感染艾滋病毒的AGYW患者的反应性生物标记物和抗逆转录病毒治疗(ART)依从性和病毒载量。 我们将使用164名艾滋病病毒感染者的数据以及有关压力反应的信息。 2018/19年访问的生物标记物、病毒载量和ART。这项研究将为R34提供初步数据 开发和试点减轻AGYW中生理应激影响的干预措施的应用 预防艾滋病毒，改善获得护理和治疗的机会。这项研究与美国国立卫生研究院的艾滋病毒/艾滋病研究一致 优先推进交叉研究领域和妇幼传染病处 (MPIDB)预防青少年艾滋病毒的优先事项。

PROJECT SUMMARY/ABSTRACT Adolescent girls and young women (AGYW) remain at very high risk of HIV acquisition in sub-Saharan Africa and this increased risk is tied to social and interpersonal factors. Few studies in low- and middle-income countries have collected stress-responsive biomarkers to understand biological processes, such as the physiological stress response, that may underlie the increased risk of HIV infection observed among AGYW. Evidence is mounting for the association between social determinants of health and the physiological effects of stress in the United States and Europe, but it is lacking in sub-Saharan Africa. Stress has been associated with social determinants of health and with adverse outcomes in individuals with HIV; however, these studies are among adults and with small sample sizes and evidence is limited regarding incident HIV infection. The overarching objective of the proposed project is to generate preliminary evidence examining the relationships between psychosocial stressors; biological stress; and HIV prevention, care, and treatment in AGYW in South Africa. The project objective will be met through three Specific Aims: Using an existing and unique data source (HIV Prevention Trials Network 068 study) with information on psychosocial stressors, stress responsive biomarkers, and HIV incidence among a cohort of 2,533 AGYW that have been followed for 9 years in South Africa, in Aim 1 we will assess associations between acute (physical and sexual intimate partner violence, traumatic events) and chronic (food insecurity, depression, and low parental support) psychosocial stressors with stress-responsive immune biomarkers (C-reactive protein [CRP] titers, herpes simplex virus type 1 (HSV-1) titers, and cytomegalovirus (CMV)) among AGYW. We will use data from 1,517 AGYW with biomarker information available at the 2018/19 visit and will explore effect modification by HIV status and correlations with perceived stress. In Aim 2 we will conduct a case-cohort study of 849 AGYW to estimate the association between stress-responsive biomarkers during adolescence with sexual behavior and incident HIV infection at later time points. We will retrospectively test existing, stored biospecimens for cases and controls to assess these relationships. In Aim 3 we will estimate associations between stress- responsive biomarkers and antiretroviral therapy (ART) adherence and viral load among AGYW with HIV. We will use data from 164 AGYW with HIV along with information available about stress-responsive biomarkers, viral load, and ART from the 2018/19 visit. This study will provide preliminary data for an R34 application to develop and pilot an intervention mitigating the effects of physiological stress among AGYW to prevent HIV and improve access to care and treatment. The research aligns with the NIH HIV/AIDS research priority to advance cross-cutting areas of research and the Maternal and Pediatric Infectious Disease Branch (MPIDB) priority of preventing HIV in adolescents.