Cardiovascular Disease Risk in HIV-infected Women: Sex-Specific Mechanisms of Risk and Risk Reduction among REPRIEVE Trial Participants

 描述（由申请人提供）：HIV感染者面临心血管疾病（CVD）的风险显著增加，即使通过联合抗逆转录病毒治疗（cART）抑制病毒血症。HIV相关CVD风险的潜在机制尚未完全了解，也没有针对这一人群的心脏保护护理的具体指南。确定和减少感染艾滋病毒的妇女的心血管疾病风险是一项特别的挑战。感染艾滋病毒的妇女在选定的传统心血管疾病风险因素（例如，高血压、吸烟），在临床实践中获得预防性心脏病护理的可能性低于艾滋病毒感染男子。然而，一些研究表明，感染艾滋病毒的妇女与男性一样有可能发生MI。事实上，一项大规模的美国流行病学研究表明，在HIV感染的女性中，未经调整的MI发生率略高于HIV感染的男性。此外，同一研究显示，与HIV感染男性与未感染男性（1.4）相比，HIV感染女性与未感染女性（2.89）的MI校正相对风险显著更高。这项拟议的研究旨在确定CVD风险和降低HIV风险的性别特异性机制，解决NIH的研究重点。重要的是，拟议的研究利用了HIV相关CVD领域最大的一级预防试验的基础设施：预防HIV血管事件的随机试验（REPRIEVE，A5332）。REPRIEVE试验目前正在启动，将在6500名40-75岁的HIV感染者中测试他汀类药物治疗是否能减少临床心血管事件。他汀类药物治疗对HIV有吸引力，因为它既能降低LDL胆固醇水平，又能抑制致动脉粥样硬化的免疫激活，这在接受cART的HIV患者中持续存在。我们小组和其他人的工作表明，艾滋病毒感染的女性（与艾滋病毒感染的男性相比）的免疫激活最高，特别是那些经历更年期的女性。通过拟议的项目，我们将评估免疫激活是否对整个生殖衰老范围内的HIV感染妇女的CVD风险有独特的贡献，以及他汀类药物如何通过对这一途径的影响降低CVD风险。这些问题的答案将影响CVD预测和预防策略的发展，这些策略针对全球老龄女性HIV感染人群（约1700万）。为了最大限度地阐明HIV中性别特异性CVD机制，我们还将设计、实施和评估循证教育/宣传招募活动的有效性，以提高REPRIEVE试验中的女性入组率。

 DESCRIPTION (provided by applicant): HIV-infected individuals face a markedly increased risk of cardiovascular disease (CVD), even when viremia is suppressed by combined antiretroviral therapy (cART). Mechanisms underlying HIV-associated CVD risk are incompletely understood and specific guidelines on cardioprotective care for this population are not available. Characterizing and reducing CVD risk among HIV-infected women represents a particular challenge. HIV-infected women have a lower prevalence of select traditional CVD risk factors (e.g., hypertension, smoking) and are less likely than HIV-infected men to be offered preventive cardiac care in clinical practice. However, several studies suggest women with HIV are just as likely as their male counterparts to incur an MI. Indeed, a large-scale US epidemiologic study shows that among HIV-infected women, unadjusted rates of MI modestly exceed those among HIV-infected men. Moreover, the same study reveals a significantly higher adjusted relative risk of MI in HIV infected-women versus uninfected females (2.89) as compared with HIV-infected men versus uninfected males (1.4). The proposed study aims to identify sex-specific mechanisms of CVD risk and risk reduction in HIV, addressing an NIH research priority. Importantly, the proposed study leverages the infrastructure of the largest primary prevention trial in the field of HIV-associated CVD: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE, A5332). The REPRIEVE trial, now launching, will test among 6500 HIV-infected persons ages 40-75 with low traditional CVD risk scores whether statin therapy reduces clinical cardiovascular events. Statin therapy has appeal in HIV in that it both reduces LDL cholesterol levels and dampens atherogenic immune activation, which persists in persons with HIV on cART. Work from our group and others suggests immune activation is highest in HIV-infected women (vs. HIV-infected men), particularly among those women who have undergone menopause. Through the proposed project, we will assess whether immune activation contributes uniquely to CVD risk among HIV-infected women across the reproductive aging spectrum and how statins may reduce CVD risk through effects on this pathway. Answers to these questions will influence the development of CVD prediction and prevention strategies tailored to the aging female HIV-infected population worldwide (~17 million). Maximizing our power to elucidate sex-specific CVD mechanisms in HIV, we will also design, implement, and evaluate the effectiveness of an evidence-based education/awareness recruitment campaign to enhance female enrollment in the REPRIEVE trial.