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

随着有效的联合抗逆转录病毒疗法(ART)的预期寿命延长，更多携带艾滋病毒的妇女 (WWH)正进入更年期。WWH经历更频繁和更严重的血管运动症状(VMS； 潮热和盗汗的统称)比没有感染艾滋病毒的妇女要多。更年期的转变是 还与骨质疏松/骨折等与衰老相关的合并症风险增加有关， 心血管疾病和神经认知障碍对WWH的影响不成比例。更年期 激素疗法(HT)是VMS最有效的治疗方法，但利用率低，且从未 在WWH上进行了研究。我们提出了一项随机、双盲、安慰剂对照、2x2交叉试验(n=80)。 评价经皮雌激素联合口服黄体酮与安慰剂治疗对症的疗效 围绝经期和绝经早期合并VMS的WWH(目标1)。我们还将比较高温与高温的效果。 安慰剂对神经认知功能、情绪、睡眠和生活质量的影响 已在更年期期间的WWH中进行了专门研究(目标2)。羟色胺具有显著的抗炎作用； 因此，我们将评估羟色胺对骨和心脏代谢健康生物标记物的影响，并检测 全身炎症的作用(目标3)。最后，我们将使用 通过基于诱导转录的测序(EDITS)分析检测包膜，提供前瞻性 用实验数据验证WWH后可诱导的HIV宿主增加的观测数据结果 更年期(探索性目标)。我们的建议利用了艾滋病诊所的资源和基础设施 试验组(ACTG)。资格标准和终端也设计为与MsFLASH保持一致 (更年期策略：寻找持久的症状答案和健康试验)网络试验允许 未来的分析比较了携带和不携带HIV的妇女的羟色胺反应。我们的研究结果将提供 关于羟色胺在预防衰老相关并发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，这次试验将为今后的工作奠定基础。 高血压与非激素治疗VMS及预防合并症的研究 老化的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.