Bone Mineral Density in a Cohort of Young Women using Depo-provera and Tenofovir

 描述(申请人提供)：在过去的二十年里，人类免疫缺陷病毒(HIV)已经成为一种慢性病，而不是一种致命的疾病)。这归因于抗逆转录病毒疗法(ART)的使用，它延长了艾滋病毒感染者的预期寿命。更新的治疗方案，如含有ART的替诺福韦(TDF)，加上更简单的每日一次给药方案，有望进一步提高存活率。然而，许多研究表明，与普通人群相比，艾滋病毒感染者骨密度(BMD)损失加快，骨量减少和骨质疏松症的发生率更高，并随后发生骨折。目前尚不清楚艾滋病毒感染者的骨密度损失中有多少是由于艾滋病毒感染本身造成的，也不知道有多少可以归因于抗逆转录病毒疗法的后果。在不同的抗逆转录病毒药物中，替诺福韦(TDF)的潜在作用尤其令人关注。在育龄妇女中，避孕措施的选择也可能影响骨骼健康。代孕酮醋酸酯(DMPA，Depo Provera)是一种广泛使用的以孕酮为基础的避孕方法，也与降低骨密度有关。由于DMPA和TDF似乎与降低的BMD独立相关，这引起了人们的担忧，即同时使用这两种药物可能会增强彼此的效果，并导致与早期骨质疏松症和脆性骨折相关的长期发病风险增加 在资源有限的情况下感染艾滋病毒的妇女。到目前为止，还没有研究检查TDF和DMPA的联合作用。为了解决这一差距，我们建议研究DMPA和TDF在乌干达坎帕拉及其周边地区艾滋病毒护理中心和普通医疗机构接受治疗的18至30岁年轻乌干达女性在两年时间内对骨密度的联合影响。此外，该项目将确定在2年的随访期内，接受TDF ART治疗的患者的骨密度丢失和骨转换是否与同时使用DMPA有关。主要结果将是腰椎骨密度较基线的百分比变化，这将在基线、6、12、18和24个月时使用双能量X射线吸收测量仪进行测量。项目成果有望为同时使用DMPA和基于TDF的抗逆转录病毒疗法的非洲年轻感染艾滋病毒的脆弱人群提供有关骨密度丢失的新的和重要的临床相关信息。这项研究有可能为艾滋病毒感染妇女的抗逆转录病毒治疗和避孕指南的政策提供信息，特别是在资源有限的情况下。研究结果还将成为未来对接受抗逆转录病毒治疗的感染女性进行更安全避孕的研究的基础，以及关于维生素D和补钙等前瞻性干预措施的研究，这些干预可能会将骨丢失的风险降至最低。

 DESCRIPTION (provided by applicant): Over the past two decades, Human Immunodeficiency Virus (HIV) has become a chronic condition rather than a fatal disease). This is attributable to use of antiretroviral therapy (ART) which has increased life expectancy of HIV infected individuals. Newer treatment options like tenofovir (TDF) containing ART with simpler once-a-day dosing regimens promise even further increases in survival. A number of studies have however demonstrated accelerated Bone Mineral Density (BMD) loss, higher rates of osteopenia and osteoporosis, and subsequent fractures among HIV-infected individuals compared to the general population. It is not yet known how much of the BMD loss among HIV infected patients is due to HIV infection per se and how much can be attributed to the consequences of ART. Of the different anti-retroviral drugs, the potential effect of tenofovir (TDF) is particularly concerning. Among women of reproductive age, the choice of contraception may also impact bone health. Depot medroxyprogesterone acetate (DMPA, Depo Provera), a widely used progesterone-based contraceptive method has also been associated with reduced BMD. Since DMPA and TDF appear to be independently associated with reduced BMD, this raises concerns that concurrent use of these two agents may potentiate each other's effect and lead to increased long term risk of morbidity related to early osteoporosis and fragility fractures among HIV infected women in resource limited settings. To date, no studies have examined the combined effect of TDF and DMPA. To address this gap, we propose to study the combined effect of DMPA and TDF on BMD over a two year period among young Ugandan women aged 18 to 30 years attending HIV care centers and general health facilities in and around Kampala, Uganda. In addition, the project will determine whether BMD loss and bone turnover with TDF ART initiation over a 2 year follow-up period, is greater with concomitant use of DMPA. The primary outcome will be percent change from baseline in lumbar spine BMD which will be measured at baseline, 6, 12, 18, and 24 months using dual energy x-ray absorptiometry. Project results are expected to contribute novel and important clinically relevant information about BMD loss in a vulnerable population of young HIV infected African women concurrently using DMPA and TDF based ART. The study has potential to inform policy on ART treatment and contraceptive guidelines for HIV infected women particularly in resource limited settings. Results will also form the basis for future studies on safer contraception for infected women on ART, as well as studies on proactive interventions like vitamin D and calcium supplementation that may minimize risk of bone loss.