他汀类药物对全球 HIV 感染者队列中重大非心血管疾病事件发生率的影响：随机对照试验。

IF 12.8 1区医学 Q1 IMMUNOLOGY

Lancet Hiv Pub Date : 2025-04-01 DOI:10.1016/S2352-3018(24)00345-X

Marissa R Diggs, Triin Umbleja, Sara McCallum, Markella V Zanni, Sarah M Chu, Kathleen V Fitch, Gerald S Bloomfield, Judith S Currier, Esteban Martinez, Philip E Castle, Aya Awwad, Mamta K Jain, Roger Bedimo, Bronwyn Hendricks, Jose Narrea, Vincente Estrada, Jorge Pinto, Judith A Aberg, Carlos D Malvestutto, Carl J Fichtenbaum, Michael T Lu, Heather J Ribaudo, Pamela S Douglas, Steven K Grinspoon

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引用次数: 0

摘要

背景：考虑到他汀类药物除降脂外的多效作用，他汀类药物可能对其他非心血管疾病（non- cvd）产生积极影响。在这项研究中，我们前瞻性地评估了他汀类药物对全球HIV感染者非心血管疾病事件及其发病率的影响。方法：预防HIV患者血管事件的随机试验(REPRIEVE；ClinicalTrials.gov （NCT02344290）是一项匹伐他汀预防心血管疾病的随机、安慰剂对照试验，于2015年至2023年在12个国家的145个研究点进行，目前已完成。在这项对REPRIEVE预先指定的次要结局的分析中，我们使用Cox比例风险回归，按性别和CD4细胞计数分层，评估了每日4mg匹伐他汀（与安慰剂相比）对主要非心血管事件（包括艾滋病定义事件、非艾滋病定义癌症、肾脏疾病和肝脏疾病）和抗逆转录病毒治疗策略时机（START）试验结果（包括心血管疾病在内的艾滋病患者发病率的集体测量）的影响。研究结果：在7769名HIV感染者中（匹伐他汀组3888人，安慰剂组3881人），6402名参与者完成了研究（每组3201人）。在中位5.6年（IQR 4.7 - 6.3）的随访中，匹伐他汀组的主要非心血管事件发生率为9.17 / 1000人-年，安慰剂组为9.90 / 1000人-年(风险比[HR]，病因特异性：0.92,95% CI 0.76 - 1.13；p = 0·44)。匹伐他汀组START结局的发生率为15.2 / 1000人-年，安慰剂组为18.3 / 1000人-年(HR 0.83, 95% CI 0.71 - 0.97；p=0·016)，由CVD效应驱动。在安慰剂组中，START试验结果中非艾滋病定义性癌症和心血管疾病的发生率最高（5.83 / 1000人年和5.48 / 1000人年），而艾滋病定义性事件的发生率较低（3.60 / 1000人年），并且在全球各地区有所不同。与安慰剂相比，匹伐他汀的CVD发病率较低（每1000人年3.36例），但非艾滋病定义的癌症仍然很高（每1000人年5.40例）。非艾滋病定义的癌症是两组患者死亡的主要原因。解释：在全球HIV感染者队列中，匹伐他汀治疗未显示非心血管疾病事件（包括非艾滋病定义的癌症）的显著减少。这些发现概述了他汀类药物用于预防非心血管疾病的局限性，强调了对此类事件的其他策略的需求。资助：美国国立卫生研究院、美国科华制药公司、吉利德科学公司和ViiV医疗保健公司。

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Statin effects on the incidence of major non-cardiovascular disease events among a global cohort of people with HIV: a randomised controlled trial.

Background: Given the pleiotropic effects of statins beyond lipid-lowering, statins might positively impact other, non-cardiovascular diseases (non-CVDs). In this study, we prospectively assessed statin effects on non-CVD events and their incidence among people with HIV globally.

Methods: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE; ClinicalTrials.gov, NCT02344290) was a randomised, placebo-controlled trial of pitavastatin for CVD prevention took place from 2015 to 2023 at 145 research sites in 12 countries and is completed. In this analysis of prespecified secondary outcomes of REPRIEVE, we assessed effects of pitavastatin 4 mg daily (vs placebo) on major non-CVD events (including AIDS-defining events, non-AIDS-defining cancers, renal disease, and liver disease) and the Strategic Timing of Antiretroviral Treatment (START) trial outcome (a collective measure of morbidity including CVD among people with HIV) using Cox proportional hazards regression, stratified by sex and CD4 cell count.

Findings: Among the 7769 people with HIV enrolled (3888 in the pitavastatin group and 3881 in the placebo group), 6402 participants completed the study (3201 in each group). Over a median 5·6 years (IQR 4·7-6·3) of follow-up, the incidence of major non-CVD events was 9·17 per 1000 person-years in the pitavastatin group and 9·90 per 1000 person-years in the placebo group (hazard ratio [HR], cause-specific: 0·92, 95% CI 0·76-1·13; p=0·44). The incidence of the START outcome was 15·2 per 1000 person-years in the pitavastatin and 18·3 per 1000 person-years in the placebo group (HR 0·83, 95% CI 0·71-0·97; p=0·016), driven by the effect on CVD. In the placebo group, incidences of the non-AIDS-defining cancer and CVD components of the START Trial outcome were highest (5·83 per 1000 person-years and 5·48 per 1000 person-years) whereas AIDS-defining events were less frequent (3·60 per 1000 person-years), and varied across global regions. With pitavastatin, the incidence of CVD was lower compared with placebo (3·36 per 1000 person-years), however non-AIDS-defining cancers remained high (5·40 per 1000 person-years). Non-AIDS-defining cancers were the leading cause of mortality for both groups.

Interpretation: Among a global cohort of people with HIV, treatment with pitavastatin showed no major reduction in non-CVD events, including non-AIDS-defining cancers. These findings outline the limitations of statin therapy for the prevention of non-CVD, highlighting the need for other strategies for such events.

Funding: National Institutes of Health, Kowa Pharmaceuticals America, Gilead Sciences, and ViiV Healthcare.

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来源期刊

Lancet Hiv IMMUNOLOGYINFECTIOUS DISEASES&-INFECTIOUS DISEASES

CiteScore

19.90

自引率

4.30%

发文量

368

期刊介绍： The Lancet HIV is an internationally trusted source of clinical, public health, and global health knowledge with an Impact Factor of 16.1. It is dedicated to publishing original research, evidence-based reviews, and insightful features that advocate for change in or illuminates HIV clinical practice. The journal aims to provide a holistic view of the pandemic, covering clinical, epidemiological, and operational disciplines. It publishes content on innovative treatments and the biological research behind them, novel methods of service delivery, and new approaches to confronting HIV/AIDS worldwide. The Lancet HIV publishes various types of content including articles, reviews, comments, correspondences, and viewpoints. It also publishes series that aim to shape and drive positive change in clinical practice and health policy in areas of need in HIV. The journal is indexed by several abstracting and indexing services, including Crossref, Embase, Essential Science Indicators, MEDLINE, PubMed, SCIE and Scopus.