Hormone Therapy for Peri- and Postmenopausal Women with HIV (HoT)

感染艾滋病毒的围绝经期和绝经后妇女的激素治疗 (HoT)

• 批准号: 10698682
• 负责人: Sara Hurtado Bares
• 金额: $ 79.79万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10698682
• 关键词: AIDS clinical trial group; Acceleration; Affect; Aging; Anti-Inflammatory Agents; Biological Assay; Biological Markers; Biometry; Cardiovascular Diseases; Caring; Cell Communication; Chronic; Cross-Over Trials; Data; Detection; Development; Double-Blind Method; Down-Regulation; Eligibility Determination; Endocrinology; Estrogen Therapy; Estrogens; Experimental Models; Fracture; Future; Genetic Transcription; Goals; Gynecology; HIV; HIV-1; Health; Heart Diseases; Hormonal Change; Hot flushes; Immunology; Impaired cognition; Inflammation; Infrastructure; Life Expectancy; Measures; Mediating; Medicine; Menopausal Symptom; Menopausal Syndrome; Menopause; Mental Health; Moods; Neurocognition; Neurocognitive; Neurocognitive Deficit; Night Sweating; Oral; Osteoporosis; Outcome; Pathway interactions; Perimenopause; Persons; Placebo Control; Placebos; Postmenopause; Prevention; Process; Progesterone; Property; Psychology; Quality of life; RNA; Randomized; Research; Research Personnel; Residual state; Resources; Risk; Role; Sleep; Symptoms; Virus; Visit; Woman; Women' s Health; antiretroviral therapy; bone; bone loss; bone turnover; cancer risk; cardiometabolism; cardiovascular risk factor; comorbidity; design; effective therapy; efficacy evaluation; endothelial dysfunction; experience; high risk; hormone therapy; immune activation; improved; innovation; interest; menopausal hormone therapy; monocyte; multidisciplinary; neurocognitive disorder; older women; prevent; prospective; reproductive senescence; symptom treatment; systemic inflammatory response; therapy adherence; transdermal estrogen; treatment response; vasomotor symptoms; virology

As life expectancy increases with effective combination antiretroviral therapy (ART), more women with HIV (WWH) are reaching menopause. WWH experience more frequent and severe vasomotor symptoms (VMS; the collective term for hot flashes and night sweats) than women without HIV. The menopausal transition is also associated with increasing risk of aging-related comorbidities such as osteoporosis/fracture, cardiovascular disease and neurocognitive impairment that disproportionately affect WWH. Menopausal hormone therapy (HT) is the most effective treatment for VMS; however, utilization is low and HT has never been studied in WWH. We propose a randomized, double-blind, placebo-controlled, 2x2 cross-over trial (n=80) to evaluate the efficacy of HT (transdermal estrogen plus oral progesterone) versus placebo for symptomatic peri- and early post-menopausal WWH with VMS (Aim 1). We will also compare the effects of HT versus placebo on neurocognitive function, mood, sleep and quality of life using a battery of assessments that have been studied specifically in WWH during menopause (Aim 2). HT has noted anti-inflammatory properties; therefore, we will evaluate the effect of HT on biomarkers of bone and cardiometabolic heath and examine the role of systemic inflammation (Aim 3). Lastly, we will measure effects of HT on the HIV reservoir using the Envelope Detection by Induced Transcription-based Sequencing (EDITS) assay, providing prospective experimental data to validate observational data findings of increased inducible HIV reservoir in WWH after menopause (Exploratory Aim). Our proposal leverages the resources and infrastructure of the AIDS Clinical Trials Group (ACTG). Eligibility criteria and endpoints have also been designed to align with MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health Trials) network trials to allow for future analyses comparing HT response in women with and without HIV. The results of our study will provide critical information about the role of HT in prevention of aging-related comorbidities and will elucidate whether systemic inflammation is a modifiable mechanistic pathway. Further, this trial will set the groundwork for future research comparing HT to non-hormonal therapies for treatment of VMS and prevention of comorbidities in aging WWH.

随着有效的抗逆转录病毒联合疗法（ART）延长预期寿命， (WWH)都快到更年期了WWH经历更频繁和严重的血管痉挛症状（VMS; 潮热和盗汗的统称）比没有艾滋病毒的妇女多。更年期是 也与年龄相关的合并症如骨质疏松症/骨折的风险增加有关， 心血管疾病和神经认知障碍，不成比例地影响WWH。更年期 激素治疗（HT）是VMS最有效的治疗方法;然而，利用率低，HT从未 在WWH学习过。我们提出了一项随机、双盲、安慰剂对照、2x2交叉试验（n=80） 评价HT（经皮雌激素加口服孕酮）与安慰剂相比对有症状的 绝经后和绝经后早期WWH伴VMS（目的1）。我们还将比较HT与 安慰剂对神经认知功能、情绪、睡眠和生活质量的影响，使用一系列评估， 在绝经期间专门研究了WWH（目标2）。HT具有显著的抗炎特性; 因此，我们将评估HT对骨和心脏代谢健康生物标志物的影响，并检查HT对骨和心脏代谢健康的影响。 全身炎症的作用（目的3）。最后，我们将使用 通过基于诱导转录的测序（EDITS）测定的包膜检测，提供了前瞻性的 实验数据，以验证观察数据发现，在WWH中， 绝经期（探索性目的）。我们的提案利用艾滋病临床研究所的资源和基础设施， 试验组（ACTG）。合格标准和终点的设计也与MsFLASH一致 （更年期策略：寻找症状和健康试验的持久答案）网络试验， 未来的分析比较HT反应的妇女与艾滋病毒。我们的研究结果将提供 关于HT在预防衰老相关合并症中的作用的关键信息，并将阐明 全身性炎症是一种可改变的机制途径。此外，这次审判将为未来的审判奠定基础。 比较HT与非激素疗法治疗VMS和预防合并症的研究 老化WWH。