Impact of Concurrent Initiation of DMPA Contraception and Tenofovir PrEP on Bone Loss in Young Women

同时开始 DMPA 避孕和替诺福韦 PrEP 对年轻女性骨质流失的影响

基本信息

批准号：
9901549
负责人：
Renee A. Heffron
金额：
$ 64.87万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-05-17 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9901549
关键词：
AIDS prevention Address Adolescence Adverse effects Affect Africa African Age Albumins Amenorrhea Anatomy Anti-Retroviral Agents Barrier Contraception Biochemical Bone Density Bone Growth C-telopeptide Clinical Contraceptive Agents Contraceptive methods Creatinine Dual-Energy X-Ray Absorptiometry Economics Elderly Enrollment Epidemiologic Methods Estradiol Estrogens Exposure to Face Fracture Fumarates Glucose Gonadal Steroid Hormones Growth HIV HIV risk Heterosexuals Hip region structure Injectable Injury to Kidney Intervention Investigation Kidney Knowledge Life Link Measures Mediation Medroxyprogesterone 17-Acetate Metabolism Methods Minerals Modeling N-terminal PTH gene Pathway interactions Pharmaceutical Preparations Prevention strategy Procollagen Prospective cohort Proteins Public Health Radiology Specialty Recommendation Renal function Research Safety Serum Tenofovir Testing Time Trabecular Bone Score Uganda Vertebral column Vitamin D-Binding Protein Vitamin D2 Wages Woman Women&apos s Health Wrist authority base bone bone health bone loss bone mass bone metabolism bone turnover condoms critical period emerging adult experience fracture risk global health hormone binding protein indexing inorganic phosphate nephrotoxicity osteoporosis with pathological fracture pre-exposure prophylaxis pregnancy prevention prevent safety outcomes sex side effect skeletal unintended pregnancy young woman

项目摘要

ABSTRACT The primary objective of this proposal is to conduct a comprehensive study of bone safety with concurrent use of tenofovir (TDF)-based pre-exposure prophylaxis (PrEP) for HIV prevention and depot medroxyprogesterone acetate (DMPA) use for pregnancy prevention. Bone safety with the concurrent use of these agents is extremely relevant for young women in settings with high HIV burden and frequent use of DMPA, such as Uganda. As single interventions, both of these agents are known to reduce bone mineral density, a key marker for fracture risk.Bone fractures often result in lost wages and economic stability, severe consequences for young women. Furthermore, reductions in bone mass before the age of 25 can yield reduced peak bone mass, a frequent correlate of osteoporotic fracture later in life. Recent approvals of TDF-based PrEP from Sub-Saharan African drug authorities will accelerate its roll-out, making studies of its effects when added on top of other agents extremely timely and important for public health messaging. We hypothesize that there are direct links from concurrent TDF and DMPA use to bone loss through subclinical kidney injury or hypoestrogenism and will comprehensively assess markers of both mechanistic pathways. We will enroll a prospective cohort of 400 HIV- uninfected women ages 16-25 years initiating DMPA and condoms in Kampala, Uganda, and offer PrEP to all of them. Using radiologic, biochemical, and epidemiologic methods, the following specific aims will be addressed: 1) In a direct investigation of bone acquisition, we will use dual energy x-ray absorptiometry (DXA) to assess whether young women using TDF-based PrEP and DMPA concurrently attain lower peak bone mass over a 24- month period and have evidence of disrupted microarchitecture, relative to women using either agent singly or neither agent; 2) We will investigate whether young women concurrently using TDF-based PrEP and DMPA experience: 1) higher rates of bone turnover, a direct precursor to bone loss and 2) markers distinguishing two mechanistic pathways between TDF and DMPA use and bone mass: subclinical kidney injury and hypoestrogenism; and 3) Using mediation analysis, we will identify the degree to which the pathways through subclinical kidney injury and hypoestrogenism account for changes in bone density among women concurrently using TDF-based PrEP and DMPA. This study will be the first to comprehensively evaluate and model reductions in bone mass, changes in bone metabolism, and the pathways between bone and kidney function and bone and estrogen that are altered by the simultaneous initiation of PrEP and DMPA during a critical time point of bone maturation for young women.

抽象的该提案的主要目标是对同时使用的骨安全性进行全面研究基于替诺福韦 (TDF) 的暴露前预防 (PrEP) 用于艾滋病毒预防和长效甲羟孕酮醋酸盐（DMPA）用于预防怀孕。同时使用这些药物对骨骼的安全性非常重要与乌干达等艾滋病毒负担高且经常使用 DMPA 的地区的年轻女性相关。作为单一干预措施，这两种药物都会降低骨矿物质密度，骨矿物质密度是骨折的关键标志骨折常常导致工资损失和经济稳定，对年轻女性造成严重后果。此外，25 岁之前骨量的减少会导致峰值骨量减少，这是一种常见的现象。与晚年骨质疏松性骨折相关。撒哈拉以南非洲地区最近批准了基于 TDF 的 PrEP 药品监管机构将加速其推广，研究其与其他药物一起添加时的效果对于公共卫生信息传递极其及时且重要。我们假设存在直接链接同时使用 TDF 和 DMPA 会导致亚临床肾损伤或雌激素低下导致的骨质流失，并且会全面评估两种机制途径的标记。我们将招募一个由 400 名 HIV 患者组成的前瞻性队列在乌干达坎帕拉，未感染的 16-25 岁女性开始使用 DMPA 和安全套，并向所有人提供 PrEP 他们。使用放射学、生化和流行病学方法，将实现以下具体目标： 1) 在骨获取的直接研究中，我们将使用双能 X 射线吸收测定法 (DXA) 来评估使用基于 TDF 的 PrEP 和 DMPA 的年轻女性是否在 24 小时内同时达到较低的峰值骨量月期间，并且有证据表明，相对于单独使用药剂或使用药剂的女性，微结构被破坏既不是代理人； 2) 我们将调查年轻女性是否同时使用基于TDF的PrEP和DMPA 经验：1) 较高的骨转换率，这是骨质流失的直接前兆；2) 区分两种情况的标志物 TDF 和 DMPA 使用与骨量之间的机制途径：亚临床肾损伤和雌激素低下症; 3）使用中介分析，我们将确定途径的程度亚临床肾损伤和雌激素不足同时导致女性骨密度变化使用基于 TDF 的 PrEP 和 DMPA。这项研究将是第一个全面评估和模拟减少量的研究骨量、骨代谢的变化以及骨肾功能和骨与骨之间的通路在骨形成的关键时间点同时启动 PrEP 和 DMPA 会改变雌激素适合年轻女性的成熟。