开始抗逆转录病毒治疗接近 HIV-1 血清转化后体重的变化：一项国际队列合作研究。

Changes in bodyweight after initiating antiretroviral therapy close to HIV-1 seroconversion: an international cohort collaboration.

机构信息

Department of Hygiene, Epidemiology, and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Institute for Global Health, University College London, London, UK.

出版信息

Lancet HIV. 2024 Oct;11(10):e660-e669. doi: 10.1016/S2352-3018(24)00183-8. Epub 2024 Aug 23.

DOI:10.1016/S2352-3018(24)00183-8

PMID:39186940

Abstract

BACKGROUND

Understanding the reasons for and consequences of bodyweight change in people living with HIV initiating antiretroviral therapy (ART) is crucial to optimising long-term health and wellbeing. We aimed to examine bodyweight trends and associated factors among individuals with well estimated dates of HIV-1 seroconversion.

METHODS

In this cohort study, we pooled retrospective data from clinical records of participants in CASCADE aged 16 years and older recruited from clinics in France, Greece, the Netherlands, Spain, Sweden, the UK, and Canada. All participants had well estimated dates of HIV-1 seroconversion, seroconverted between Jan 1, 2007, and Dec 31, 2022 (HIV-1 positive antibody test within 12 months of an HIV-1 negative antibody test, or other laboratory evidence of seroconversion), initiated ART within 1 year of seroconversion, and were previously ART-naive. Participants were followed up to the time of data pooling (May 31, 2023). We modelled bodyweight changes after ART initiation by ART class, BMI categories, and other demographic characteristics using linear mixed models.

FINDINGS

Of 15 755 potentially eligible participants, 5698 met inclusion criteria. Of those, 5148 (90·3%) were assigned male at birth, 517 (9·1%) were assigned female at birth, and 33 (0·6%) had sex not known. 2778 (48·8%) participants initiated integrase strand transfer inhibitor (INSTI)-based ART regimens, 1809 (31·7%) initiated protease inhibitor-based regimens, and 1111 (19·5%) initiated non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. The majority of participants were men who have sex with men (MSM; 4519 [79·3%]). Median age at seroconversion was 33·7 years (IQR 26·9-43·2). Bodyweight changes differed significantly by ART class within all baseline BMI categories (BMI <18·5 kg/m p=0·026, BMI 18·5-24·9 kg/m p<0·0001, BMI 25·0-29·9 kg/m p=0·0021, and BMI ≥30·0 kg/m p=0·0033; ART class and BMI interaction p=0·011). Participants with BMI less than 30 kg/m on regimens including both INSTI and tenofovir alafenamide gained 4·76 kg (95% CI 4·05-5·46) or more at 3 years. Of those with baseline BMI 18·5-24·9 kg/m, 31·3% (95% CI 29·5-33·1) on INSTI-based regimens, 25·3% (23·0-27·7) on protease inhibitor-based regimens, 20·4% (18·8-22·9) on NNRTI-based regimens, 37·4% (33·9-40·9) on tenofovir alafenamide-based regimens, and 38·4% (34·6-42·1) on tenofovir alafenamide and INSTI-based regimens had gained more than 10% of their baseline bodyweight at 3 years. The greatest 3-year bodyweight gains by individuals on INSTI-based regimens and with BMI 18·5-24·9 kg/m were in women (5·63 kg [95% CI 4·92-6·35]), and people originating from sub-Saharan African (5·76 kg [5·06-6·46]), compared with MSM (3·82 kg [3·50-4·13]).

INTERPRETATION

Our findings suggest a direct effect of INSTIs and tenofovir alafenamide on bodyweight gain, rather than a return to health effect. Given the known risk for cardiometabolic disease, bodyweight management needs to be part of the overall care of individuals prescribed these drugs.

FUNDING

ViiV Healthcare UK, Janssen Pharmaceutica, and Merck Sharp & Dohme.

摘要

背景

了解开始抗逆转录病毒治疗（ART）的 HIV 感染者体重变化的原因和后果对于优化长期健康和幸福感至关重要。我们旨在研究个体体重趋势和相关因素，这些个体的 HIV-1 血清转化日期估计良好。

方法

在这项队列研究中，我们汇集了来自法国、希腊、荷兰、西班牙、瑞典、英国和加拿大诊所的年龄在 16 岁及以上的参与 CASCADE 研究的参与者的临床记录中的回顾性数据。所有参与者的 HIV-1 血清转化日期估计良好，在 2007 年 1 月 1 日至 2022 年 12 月 31 日期间血清转化（在 HIV-1 阴性抗体检测后 12 个月内 HIV-1 阳性抗体检测，或其他实验室血清转化证据），在血清转化后 1 年内开始 ART，且之前未接受过 ART。参与者随访至数据汇总（2023 年 5 月 31 日）。我们使用线性混合模型根据 ART 类别、BMI 类别和其他人口统计学特征来模拟 ART 起始后的体重变化。

结果

在 15755 名潜在合格参与者中，有 5698 名符合纳入标准。其中，5148 名（90.3%）为男性出生，517 名（9.1%）为女性出生，33 名（0.6%）性别未知。2778 名（48.8%）参与者开始使用整合酶抑制剂（INSTI）为基础的 ART 方案，1809 名（31.7%）开始使用蛋白酶抑制剂为基础的方案，1111 名（19.5%）开始使用非核苷逆转录酶抑制剂（NNRTI）为基础的方案。大多数参与者为男男性行为者（MSM；4519[79.3%]）。血清转化时的中位年龄为 33.7 岁（IQR 26.9-43.2）。体重变化在所有基线 BMI 类别中均显著不同，差异具有统计学意义（BMI <18.5 kg/m，p=0.026；BMI 18.5-24.9 kg/m，p<0.0001；BMI 25.0-29.9 kg/m，p=0.0021；BMI ≥30.0 kg/m，p=0.0033；ART 类别和 BMI 交互作用，p=0.011）。BMI 小于 30 kg/m 的参与者，在包含 INSTI 和替诺福韦艾拉酚胺的方案中，3 年后体重增加了 4.76 kg（95%CI 4.05-5.46）或更多。在基线 BMI 为 18.5-24.9 kg/m 的患者中，INSTI 为基础方案中 31.3%（95%CI 29.5-33.1），蛋白酶抑制剂为基础方案中 25.3%（23.0-27.7），NNRTI 为基础方案中 20.4%（18.8-22.9），替诺福韦艾拉酚胺为基础方案中 37.4%（33.9-40.9），替诺福韦艾拉酚胺和 INSTI 为基础方案中 38.4%（34.6-42.1）的患者，在 3 年内体重增加了 10%以上。在 INSTI 为基础方案且 BMI 为 18.5-24.9 kg/m 的患者中，体重增加最多的是女性（5.63 kg[95%CI 4.92-6.35]）和来自撒哈拉以南非洲的人（5.76 kg[5.06-6.46]），与男男性行为者（MSM；3.82 kg[3.50-4.13]）相比。