Centre for Clinical Research, Epidemiology, Modelling and Evaluation, Institute for Global Health, University College London, London, UK.
Centre for Clinical Research, Epidemiology, Modelling and Evaluation, Institute for Global Health, University College London, London, UK.
Lancet HIV. 2021 Nov;8(11):e711-e722. doi: 10.1016/S2352-3018(21)00163-6. Epub 2021 Sep 20.
Weight gain effects of individual antiretroviral drugs are not fully understood. We investigated associations between a prespecified clinically significant increase (>7%) in body-mass index (BMI) and contemporary antiretroviral use.
The International Cohort Consortium of Infectious Diseases (RESPOND) is a prospective, multicohort collaboration, including data from 17 well established cohorts and over 29 000 people living with HIV. People with HIV under prospective follow-up from Jan 1, 2012, and older than 18 years were eligible for inclusion. Each cohort contributed a predefined minimum number of participants related to the size of the specific cohort (with a minimum of 1000 participants). Participants were required to have CD4 cell counts and HIV viral load measurement in the 12 months before or within 3 months after baseline. For all antiretroviral drugs received at or after RESPOND entry, changes from pre-antiretroviral BMI levels (baseline) were considered at each BMI measurement during antiretroviral treatment. We used logistic regression to identify individual antiretrovirals that were associated with first occurrence of a more than 7% increase in BMI from pre-antiretroviral BMI. We adjusted analyses for time on antiretrovirals, pre-antiretroviral BMI, demographics, geographical region, CD4 cell count, viral load, smoking status, and AIDS at baseline.
14 703 people were included in this study, of whom 7863 (53·5%) had a more than 7% increase in BMI. Compared with lamivudine, use of dolutegravir (odds ratio [OR] 1·27, 95% CI 1·17-1·38), raltegravir (1·37, 1·20-1·56), and tenofovir alafenamide (1·38, 1·22-1·35) was significantly associated with a more than 7% BMI increase, as was low pre-antiretroviral BMI (2·10, 1·91-2·31 for underweight vs healthy weight) and Black ethnicity (1·61, 1·47-1·76 vs White ethnicity). Higher CD4 count was associated with a reduced risk of BMI increase (0·97, 0·96-0·98 per 100 cells per μL increase). Relative to lamivudine, dolutegravir without tenofovir alafenamide (OR 1·21, 95% CI 1·19-1·32) and tenofovir alafenamide without dolutegravir (1·33, 1·15-1·53) remained independently associated with a more than 7% increase in BMI; the associations were higher when dolutegravir and tenofovir alafenamide were used concomitantly (1·79, 1·52-2·11, and 1·70, 1·44-2·01, respectively).
Clinicians and people with HIV should be aware of associations between weight gain and use of dolutegravir, tenofovir alafenamide, and raltegravir, particularly given the potential consequences of weight gain, such as insulin resistance, dyslipidaemia, and hypertension.
The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort and The University of Cologne HIV Cohorts, ViiV Healthcare, and Gilead Sciences.
个体抗逆转录病毒药物引起体重增加的作用尚未完全明确。我们研究了与当前抗逆转录病毒药物使用相关的体重指数（BMI）较预治疗水平增加>7%这一临床上有意义的指标。
传染病国际队列协作组织（RESPOND）是一个前瞻性、多队列合作组织，包括来自 17 个成熟队列的数据和超过 29000 名艾滋病毒感染者。自 2012 年 1 月 1 日起接受前瞻性随访，年龄大于 18 岁的人符合纳入标准。每个队列根据特定队列的规模提供了一个预定的最小参与者数量（最低参与者数量为 1000 人）。要求参与者在基线时或基线后 3 个月内有 CD4 细胞计数和 HIV 病毒载量测量。对于在 RESPOND 入组时或之后接受的所有抗逆转录病毒药物，在接受抗逆转录病毒治疗期间，在每次 BMI 测量时都要考虑从预治疗 BMI 水平（基线）的变化。我们使用逻辑回归来确定与预治疗 BMI 水平相比 BMI 增加超过 7%的首次发生与哪些个体抗逆转录病毒药物相关。我们对接受抗逆转录病毒药物的时间、预治疗 BMI、人口统计学、地理位置、CD4 细胞计数、病毒载量、吸烟状况和基线 AIDS 进行了分析调整。
共有 14703 人纳入本研究，其中 7863 人（53.5%）的 BMI 增加超过 7%。与拉米夫定相比，使用多替拉韦（比值比[OR]1.27，95%CI 1.17-1.38）、拉替拉韦（1.37，1.20-1.56）和替诺福韦艾拉酚胺（1.38，1.22-1.35）与 BMI 增加超过 7%显著相关，预治疗 BMI 较低（体重不足与健康体重相比，2.10，1.91-2.31）和黑人种族（1.61，1.47-1.76 与白人种族相比）也是如此。较高的 CD4 计数与 BMI 增加风险降低相关（每增加 100 个细胞/μL，风险降低 0.97，0.96-0.98）。与拉米夫定相比，多替拉韦（不联合替诺福韦艾拉酚胺）（OR 1.21，95%CI 1.19-1.32）和替诺福韦艾拉酚胺（不联合多替拉韦）（OR 1.33，1.15-1.53）仍然与 BMI 增加超过 7%独立相关；当多替拉韦和替诺福韦艾拉酚胺同时使用时，相关性更高（1.79，1.52-2.11，1.70，1.44-2.01）。
临床医生和艾滋病毒感染者应注意体重增加与多替拉韦、替诺福韦艾拉酚胺和拉替拉韦使用之间的关联，特别是鉴于体重增加的潜在后果，如胰岛素抵抗、血脂异常和高血压。
圣皮埃尔布鲁塞尔艾滋病毒队列、奥地利艾滋病毒队列研究、澳大利亚艾滋病毒观察数据库、荷兰艾滋病毒治疗评估国家观察队列、欧洲艾滋病队列、法兰克福艾滋病毒队列研究、格鲁吉亚国家艾滋病健康信息系统、尼斯艾滋病毒队列、ICONA 基金会、莫德纳艾滋病毒队列、PISCIS 队列研究、瑞士艾滋病毒队列研究、瑞典 InfCare 艾滋病毒队列、皇家自由艾滋病毒队列研究、圣拉斐尔科学研究所、波恩艾滋病毒队列研究和科隆艾滋病毒队列、ViiV 医疗保健公司和吉利德科学公司。
