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.

随着预期寿命随着有效组合抗逆转录病毒疗法（ART）的增加，更多的艾滋病毒女性 （WWH）正在更年期。 WWH经历了更频繁和严重的血管舒缩症状（VMS； 与没有艾滋病毒的女性相比，潮热和夜汗的集体术语。更年期的过渡是 还与增加与衰老相关的合并症（例如骨质疏松/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VM的最有效治疗方法；但是，利用率很低，HT从来没有 在WWH中进行了研究。我们提出了一项随机，双盲，安慰剂对照的2x2交叉试验（n = 80） 评估HT（透皮雌激素加口服孕酮）与安慰剂的功效 带有VM的绝经后和早期的周期和早期（AIM 1）。我们还将比较HT与 通过一系列评估 在更年期期间在WWH中进行了专门研究（AIM 2）。 HT注意到抗炎特性。 因此，我们将评估HT对骨骼和心脏代谢性荒地生物标志物的影响，并检查 系统性炎症的作用（AIM 3）。最后，我们将使用该HT使用HT对HT对HIV库的影响 通过诱导基于转录的测序（编辑）测定法检测包络检测，提供前瞻性 实验数据以验证在WWH之后增加诱导HIV储存量增加的观察数据发现 更年期（探索目的）。我们的建议利用艾滋病临床的资源和基础设施 试验组（ACTG）。资格标准和终点也已设计为与MSFlash保持一致 （更年期策略：寻找症状和健康试验的持久答案）网络试验以允许 将来分析比较患有和没有艾滋病毒的女性的HT反应。我们的研究结果将提供 有关HT在预防衰老相关合并症中的作用的关键信息，并将阐明是否是否 系统性炎症是一种可修改的机械途径。此外，该审判将为未来树立基础 研究将HT与非激素疗法进行比较，以治疗VM和预防合并症 老化的WWH。