Impact of Concurrent Initiation of DMPA Contraception and Tenofovir PrEP on Bone Loss in Young Women
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 500
- 试验地点
- 1
- 主要终点
- The investigators will assess whether young women using TDF-based PrEP and DMPA concurrently attain lower peak bone mass over a 24-month relative to women using either agent singly or neither agent.
研究概览
简要总结
The primary objective of this study is to address critical safety questions with concurrent TDF-based PrEP and DMPA use. We hypothesize that young women using TDF-based PrEP and DMPA will have lower bone acquisition and altered bone metabolism. Bone mineral metabolism is in part regulated by the kidney, and we hypothesize that bone effects from concurrent PrEP and DMPA use will be driven by subclinical kidney injury, a known side effect of TDF, as well as DMPA-induced hypoestrogenism. To investigate our hypothesis, we will enroll a prospective cohort of approximately 500 HIV-uninfected women ages 16-25 years in Kampala, Uganda who have substantial HIV risk and are initiating DMPA or barrier method contraception. Over a 24-month period, we will offer TDF-based PrEP. We will use state-of-the-art radiologic, biochemical, and epidemiologic methods to test the hypothesis that concurrent TDF-based PrEP and DMPA use results in compounding adverse effects on bone health.
详细描述
The proposed research will investigate the hypothesis that TDF-based PrEP and DMPA initiated concurrently by HIV-uninfected women will enhance each other's effects on bone metabolism. The investigators will conduct an open-label prospective study of approximately 500 HIV-uninfected women at substantial risk for HIV-infection who are newly initiating DMPA or using condoms as their only contraceptive in Kampala, Uganda. The investigators will offer PrEP to all of these women and determine the joint effect of PrEP and DMPA on changes in bone mass (Aim 1), bone turnover, subclinical kidney injury, and hypoestrogenism (Aim 2), and conduct mediation analysis to assess the contribution of each pathway to overall losses in bone mass (Aim 3).
- The investigators will 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 The investigators will use dual energy x-ray absorptiometry (DXA) scans to measure BMD annually at 3 anatomical sites (lumbar spine, total hip, and wrist). Additionally, the investigators will derive the trabecular bone score (TBS), an index of lumbar spine trabecular microarchitecture.
- The investigators 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) subclinical kidney injury and hypoestrogenism, markers of two mechanistic pathways between TDF and DMPA use and bone mass
At baseline and 24 months, the investigators will measure:
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Markers of bone formation and resorption (e.g. NTX, P1NP, serum intact parathyroid hormone, total and bioavailable 25-OH-vitamin D)
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Markers of kidney function (phosphate, glucose, creatinine, total protein, albumin) and
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Markers of estrogen (serum estradiol, sex hormone binding protein, and the occurrence of amenorrhea) Hypothesis: Relative to women using DMPA only and PrEP only, women concurrently using TDF-based PrEP and DMPA will have increased bone turnover markers and PTH. In addition, women concurrently using TDF-based PrEP and DMPA will have more frequent subclinical kidney injury (relative to women without tenofovir exposure) and reduced serum estrogen (relative to women without DMPA exposure).
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Using mediation analysis, the investigators 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 The investigators will conduct mediation analysis to determine the degree to which changes in the pathways through subclinical kidney injury, hypoestrogenism and the combination of these pathways account for changes in bone density.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Factorial
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 25 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Inclusion criteria:
- •Age 16-25
- •If age 16-17:
- •qualification as an emancipated minor (due to past pregnancy, being married, having a child, or catering for their own livelihood) or a mature minor (due to having a sexually transmitted infection) or able to have a parent/guardian provide informed consent
- •HIV-uninfected
- •Initiated DMPA within the past 90 days or using condoms only for contraception
- •Willing and able to provide written informed consent
- •Not planning to get pregnant in the next 24 months
- •Sexually active
- •Planning to remain in the study area for the next 2 years
排除标准
- •Exclusion criteria:
- •Currently enrolled in a biomedical HIV-1 prevention study
- •Current or prior use of PrEP consecutively in the last 3 months
- •Abnormal renal function (creatinine clearance <60 min/ml)
- •Hepatitis B infection
- •Currently pregnant or breastfeeding
- •Current DMPA use for longer than 90 days
- •Use of implant, IUD, or oral contraceptives
- •Past hysterectomy, oophorectomy, or tubal ligation
- •Current or recent history of primary or secondary amenorrhea
- •Taking medications known to interfere with bone metabolism (steroids, anti-convulsants, bisphosphonates, cancer drugs).
- •Has any other condition that would preclude the ability to provide informed consent, make study participation unsafe, complicate the interpretation of study findings or otherwise interfere with achievement of the study objectives, in the investigator's discretion.
研究组 & 干预措施
DMPA and no PrEP
干预措施: DMPA (Drug)
DMPA and PrEP
干预措施: FTC/TDF and DMPA (Combination Product)
Condoms only and PrEP
干预措施: FTC/TDF (Drug)
Condoms only and no PrEP
干预措施: Neither DMPA nor FTC/TDF (Other)
结局指标
主要结局
The investigators will assess whether young women using TDF-based PrEP and DMPA concurrently attain lower peak bone mass over a 24-month relative to women using either agent singly or neither agent.
时间窗: 24 months
The investigators will use dual energy x-ray absorptiometry (DXA) scans to measure BMD annually at 3 anatomical sites (lumbar spine, total hip, and wrist). Hypothesis: Relative to women using DMPA only (without tenofovir exposure) and women using PrEP only (without DMPA exposure), women concurrently using TDF-based PrEP and DMPA will have lower bone mass.
The investigators will assess whether young women using TDF-based PrEP and DMPA concurrently have evidence of disrupted microarchitecture, relative to women using either agent singly or neither agent.
时间窗: 24 months
The investigators will use dual energy x-ray absorptiometry (DXA) scans to derive the trabecular bone score (TBS), an index of lumbar spine trabecular microarchitecture. Hypothesis: Relative to women using DMPA only (without tenofovir exposure) and women using PrEP only (without DMPA exposure), women concurrently using TDF-based PrEP and DMPA will have more disruptions in bone microarchitecture.
次要结局
- The investigators will investigate whether young women concurrently using TDF-based PrEP and DMPA experience higher rates of subclinical kidney injury.(Change from Baseline at 24 months)
- The investigators will investigate whether young women concurrently using TDF-based PrEP and DMPA experience higher rates of bone turnover.(Change from Baseline at 24 months)
- Using mediation analysis, the investigators 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(24 months)
- The investigators will investigate whether young women concurrently using TDF-based PrEP and DMPA experience higher rates of hypoestrogenism.(Change from Baseline at 24 months)
研究者
Renee Heffron
Assistant Professor, Global Health and Epidemiology
University of Washington