Diggs Marissa R, Umbleja Triin, McCallum Sara, Zanni Markella V, Chu Sarah M, Fitch Kathleen V, Bloomfield Gerald S, Currier Judith S, Martinez Esteban, Castle Philip E, Awwad Aya, Jain Mamta K, Bedimo Roger, Hendricks Bronwyn, Narrea Jose, Estrada Vincente, Pinto Jorge, Aberg Judith A, Malvestutto Carlos D, Fichtenbaum Carl J, Lu Michael T, Ribaudo Heather J, Douglas Pamela S, Grinspoon Steven K
Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Center for Biostatistics in AIDS Research, Harvard T H Chan School of Public Health, Boston, MA, USA.
Lancet HIV. 2025 Apr;12(4):e261-e272. doi: 10.1016/S2352-3018(24)00345-X.
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.
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.
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.
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.
National Institutes of Health, Kowa Pharmaceuticals America, Gilead Sciences, and ViiV Healthcare.
鉴于他汀类药物除降脂作用外还有多效性，其可能对其他非心血管疾病产生积极影响。在本研究中，我们前瞻性地评估了他汀类药物对全球艾滋病毒感染者非心血管疾病事件及其发病率的影响。
预防艾滋病毒血管事件随机试验（REPRIEVE；ClinicalTrials.gov，NCT02344290）是一项2015年至2023年在12个国家的145个研究地点进行的关于匹伐他汀预防心血管疾病的随机、安慰剂对照试验，现已完成。在对REPRIEVE预先设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4毫克匹伐他汀（与安慰剂相比）对主要非心血管疾病事件（包括艾滋病界定事件、非艾滋病界定癌症、肾脏疾病和肝脏疾病）以及抗逆转录病毒治疗时机（START）试验结局（艾滋病毒感染者包括心血管疾病在内的发病率综合指标）的影响。
在纳入的7769名艾滋病毒感染者中（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）。在中位随访5.6年（四分位间距4.7 - 6.3年）期间，匹伐他汀组主要非心血管疾病事件的发病率为每1000人年9.17例，安慰剂组为每1000人年9.90例（病因特异性风险比[HR]：0.92，95%置信区间0.76 - 1.13；p = 0.44）。匹伐他汀组START试验结局的发病率为每1000人年15.2例，安慰剂组为每1000人年18.3例（HR 0.83，95%置信区间0.71 - 0.97；p = 0.016），这是由对心血管疾病的影响所致。在安慰剂组中，START试验结局的非艾滋病界定癌症和心血管疾病成分的发病率最高（分别为每1000人年5.83例和5.48例），而艾滋病界定事件的发病率较低（每1000人年3.60例），且在全球各地区有所不同。使用匹伐他汀时，心血管疾病的发病率低于安慰剂组（每1000人年3.36例），然而非艾滋病界定癌症的发病率仍然很高（每1000人年5.40例）。非艾滋病界定癌症是两组死亡的主要原因。
在全球艾滋病毒感染者队列中，使用匹伐他汀治疗并未使包括非艾滋病界定癌症在内的非心血管疾病事件大幅减少。这些发现概述了他汀类药物治疗预防非心血管疾病的局限性，凸显了针对此类事件采取其他策略的必要性。
美国国立卫生研究院、科瓦美国制药公司、吉利德科学公司和维泰凯医疗保健公司。
