Treatment of early hypertension in persons living with HIV for cardiovascular disease prevention in Haiti

摘要：在过去的二十年里，艾滋病毒相关的心血管疾病（CVD）在低风险人群中增加了两倍。 收入国家。高血压（HTN）是艾滋病毒感染者（PLWH）中心血管疾病的主要驱动因素。 此外，PLWH伴高血压前期（pre-HTN），由WHO定义为收缩压[SBP] 120-139 mmHg或舒张压[DBP] 80-89 mmHg的患者，其CVD事件发生率显著高于未感染者 血压水平相似的成年人尽管PLWH有可能通过以下方式降低他们的CVD风险： 在较低的血压水平开始抗高血压治疗，世卫组织建议PLWH应开始抗高血压治疗， 高血压治疗与未感染艾滋病毒的成年人相同的血压阈值。需要数据来确定 在患有前HTN的PLWH中开始降压治疗以预防CVD的可行性、获益和风险。 我们提出了一个试点试验，以评估抗高血压治疗PLWH与前HTN在海地。这 这项研究将提供关键数据，为未来针对CVD事件的确定性试验提供依据。我们将 入组250例PLWH（18-65岁），他们已接受ART治疗1-5年，病毒抑制，SBP 120-139 或DBP 80-89且未接受抗高血压治疗;将他们随机分配至“早期HTN治疗”或目前 护理标准（SOC）;并随访12个月。早期HTN治疗组的参与者将开始 立即服用抗高血压药物（海地的一线抗高血压药物）。SOC组的受试者将启动 只有当他们发展为HTN（SBP >140或DBP >90）时才能服用。我们假设早期HTN治疗 不影响病毒抑制，与 Soc. 主要目的：评估PLWH伴前HTN患者开始抗高血压治疗的可行性。 可行性结果包括入组和保留数据、启动重复性研究的比例以及增量 两组间12个月时SBP的变化。我们有>80%的把握度检测SBP > 4的变化差异 研究组间mmHg。 次要目标：还审查以下成果和措施： a. 12个月时研究组之间的病毒抑制比较（定义为HIV-1 RNA < 1000拷贝/ml） B. 6个月和12个月时研究组之间的HIV药物依从性比较 C. 12个月时研究组之间的不良事件比较 D.通过与一部分参与者和提供者的深入访谈评估可接受性 e.在入组时测量所有参与者的CVD风险特征，包括肥胖、血脂异常、糖尿病， 吸烟、缺乏身体活动、不良饮食和10年心血管疾病风险 F.在入组时测量所有受试者中既存的心肌和血管功能障碍， ECG、超声心动图和血管超声

ABSTRACT: HIV-associated cardiovascular disease (CVD) has tripled over the past two decades in low- income countries. Hypertension (HTN) is a major driver of CVD among persons living with HIV (PLWH). Moreover, PLWH with prehypertension (pre-HTN), defined by WHO as systolic blood pressure [SBP] 120-139 mm Hg or diastolic BP [DBP] 80-89 mm Hg, have significantly higher rates of CVD events than uninfected adults with similar BP levels. Despite the possibility that PLWH could potentially reduce their CVD risks by initiating antihypertensive treatment at lower BP levels, WHO recommends that PLWH should initiate anti- hypertension treatment at the same BP threshold as adults without HIV. Data are needed to determine the feasibility, benefits and risks of initiating antihypertensive treatment in PLWH with pre-HTN for CVD prevention. We propose a pilot trial to evaluate antihypertensive treatment among PLWH with pre-HTN in Haiti. This study will provide critical data that will inform a future definitive trial powered for incident CVD events. We will enroll 250 PLWH (18-65 years) who have been on ART for 1-5 years with viral suppression and SBP 120-139 or DBP 80-89 and no antihypertensive treatment; randomize them to “early HTN treatment” or the current standard of care (SOC); and follow them for 12 months. Participants in the early HTN treatment arm will initiate amlodipine (Haiti’s first-line antihypertensive medication) immediately. Participants in the SOC arm will initiate amlodipine only if they develop HTN (SBP >140 or DBP >90). We hypothesize that early HTN treatment will not impact viral suppression and will be feasible and safe with a reduction in BP at 12 months compared to SOC. Primary Aim: To assess the feasibility of initiating antihypertensive treatment among PLWH with pre-HTN. Feasibility outcomes include enrollment and retention data, proportion who initiate amlodipine, and incremental change in SBP at 12 months between arms. We have >80% power to detect differences in change in SBP > 4 mm Hg between study arms. Secondary Aims: To also examine the following outcomes and measures: a. Viral suppression compared between study arms at 12 months (defined as HIV-1 RNA < 1000 copies/ml) b. HIV medication adherence compared between study arms at 6 and 12 months c. Adverse events compared between study arms at 12 months d. Acceptability assessed through in-depth interviews with a subset of participants and providers e. CVD risk profile measured among all participants at enrollment including obesity, dyslipidemia, diabetes, smoking, physical inactivity, poor diet, and 10-year CVD risk f. Pre-existing myocardial and vascular dysfunction measured among all participants at enrollment using ECG, echocardiography, and vascular ultrasound