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

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

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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的是对骨骼安全进行全面研究，并同时使用基于Tenofovir（TDF）的预防前预防（PREP），用于预防HIV和甲麦糖霉菌酮乙酸盐（DMPA）用于预防妊娠。这些试剂的同时使用骨安全性非常与年轻妇女相关的艾滋病毒负担高，经常使用DMPA的年轻妇女，例如乌干达。作为单一干预措施，已知这两种药物都可以降低骨矿物质密度，这是骨折的关键标记风险骨折通常会导致工资失去和经济稳定，对年轻妇女造成严重后果。此外，在25岁之前的骨骼质量减少可以产生峰值骨质质量，频繁骨质疏松性骨折的相关性在以后的生活中。最近对撒哈拉以南非洲的基于TDF的预备的批准药当局将加速其推出，并在其他代理商的顶部添加其效果研究对于公共卫生消息传递非常及时和重要。我们假设有直接链接通过亚临床肾脏损伤或低雌激素的同时使用TDF和DMPA用于骨骼损失，并将全面评估这两种机械途径的标记。我们将招募400名HIV-的预期队列未感染的16-25岁的未感染妇女在乌干达的坎帕拉启动DMPA和避孕套，并为所有人提供准备他们。使用放射学，生化和流行病学方法，将解决以下特定目标： 1）在直接研究骨骼获取时，我们将使用双能X射线吸收法（DXA）评估使用基于TDF的Prep和DMPA的年轻女性是否同时在24-- 一个月期间，有相对于使用代理人或两者都不是代理人； 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）更高的骨骼更新率，骨质流失的直接前体和2）区分两个标记 TDF和DMPA使用与骨骼质量之间的机械途径：亚临床肾脏损伤和低雌激素； 3）使用中介分析，我们将确定途径通过的程度亚临床肾脏损伤和低雌激素解释女性骨密度的变化使用基于TDF的PREP和DMPA。这项研究将是第一个全面评估和模型降低的研究在骨骼中，骨骼代谢的变化以及骨骼和肾功能与骨骼之间的途径以及在骨骼的关键时间点同时启动PREP和DMPA会改变的雌激素年轻女性的成熟。