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

随着有效的联合抗逆转录病毒治疗 (ART) 的延长，预期寿命会增加，更多女性感染艾滋病毒 （WWH）即将进入更年期。 WWH 经历更频繁和更严重的血管舒缩症状（VMS； 与未感染艾滋病毒的女性相比，潮热和盗汗的统称）。更年期的过渡是 还与骨质疏松症/骨折等与衰老相关的合并症的风险增加有关， 心血管疾病和神经认知障碍对 WWH 的影响尤为严重。更年期 激素疗法（HT）是治疗 VMS 最有效的方法；然而，利用率很低，HT 从未 在WWH进行了研究。我们提出一项随机、双盲、安慰剂对照、2x2 交叉试验 (n=80) 评估 HT（透皮雌激素加口服黄体酮）与安慰剂对症状的疗效 围绝经期和绝经后早期 WWH 与 VMS（目标 1）。我们还将比较 HT 与 使用一系列评估来评估神经认知功能、情绪、睡眠和生活质量的安慰剂 在更年期期间的 WWH 中进行了专门研究（目标 2）。 HT 具有抗炎特性； 因此，我们将评估 HT 对骨骼和心脏代谢健康生物标志物的影响，并检查 全身炎症的作用（目标 3）。最后，我们将使用以下方法测量 HT 对 HIV 储存库的影响： 通过基于诱导转录的测序 (EDITS) 检测进行包膜检测，提供前瞻性 实验数据验证WWH后可诱导HIV储存库增加的观察数据发现 更年期（探索性目标）。我们的提案利用了艾滋病临床中心的资源和基础设施 试验组（ACTG）。资格标准和终点也被设计为与 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 未来的分析将比较感染和未感染 HIV 的女性的 HT 反应。我们的研究结果将提供 关于 HT 在预防衰老相关合并症方面的作用的关键信息，并将阐明是否 全身炎症是一种可改变的机制途径。此外，这次试验将为未来奠定基础 比较 HT 与非激素疗法治疗 VMS 和预防合并症的研究 老化WWH。

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.