University of Bordeaux, National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Research Centre, Bordeaux, France.
Department of Infectious Diseases, Université Nazi Boni, Bobo-Dioulasso, Burkina Faso.
J Int AIDS Soc. 2024 Dec;27(12):e26371. doi: 10.1002/jia2.26371.
Adverse metabolic effects related to dolutegravir (DTG) are increasingly reported as countries are adopting DTG-based regimens as first-line antiretroviral therapy (ART), but there is limited data from sub-Saharan Africa. We explored changes in body weight pre- and post-switch to a DTG-based regimen and assessed the association between DTG switch and significant weight gain (SWG) defined as a ≥10% increase over a 12-month period in people living with HIV (PLHIV) on ART in West Africa.
We first included all PLHIV followed in the IeDEA West Africa cohorts between January 2017 and June 2021, with a documented switch to DTG during 2019-2021 and in care ≥36 months at the day of switch. Weight change was estimated using a two slope piecewise linear mixed model with change point at the switch date. Secondly, we emulated a sequence of target trials (ETT) based on the observational data, performing pooled logistic regression analysis to compare SWG occurrence between PLHIV who switched to DTG and those who did not.
We first included 6705 PLHIV from Burkina Faso, Côte d'Ivoire and Nigeria. Their median age at the time of switch was 48 years (IQR: 42-54) with a median follow-up of 9 years (IQR: 6-12), 63% were female. Most patients switched from efavirenz (EFV)-based ART (56.6%) and nevirapine (NVP)-based ART (30.9%). The overall post-switch annual average weight gain (AAWG) was significantly elevated at 3.07 kg/year [95% CI: 2.33-3.80] compared to the pre-switch AWG which stood at 0.62 kg/year [95% CI: 0.36-0.88]. The post-switch AWG was greater in patients previously on EFV and protease inhibitor (PI)-based ART compared to those on NVP-based ART. The pooled logistic regression analyses of a sequence of 24 ETT, including 9598 person-trials, switching to DTG was significantly associated with an SWG (aOR = 2.54; 95% CI = 2.18-2.97).
In West Africa, a 12-month DTG exposure was associated with substantial weight gain, especially in PLHIV previously on EFV and PI-based ARTs. Continuous weight monitoring and metabolic profiling is imperative in HIV cohorts to delineate the long-term cardiometabolic impact of DTG as patients with, or at elevated risk for cardiovascular diseases might benefit from alternative ART regimens.
随着各国开始将多替拉韦（DTG）为基础的方案作为一线抗逆转录病毒治疗（ART），与 DTG 相关的不良代谢影响的报道越来越多，但撒哈拉以南非洲地区的数据有限。我们探讨了在转换为 DTG 为基础的方案前后体重的变化，并评估了在西非人免疫缺陷病毒（HIV）感染者（PLHIV）中，DTG 转换与显著体重增加（SWG）之间的关联，SWG 定义为在接受 ART 治疗的 PLHIV 中，在 12 个月内体重增加≥10%。
我们首先纳入了 2017 年 1 月至 2021 年 6 月期间在 IeDEA 西非队列中接受治疗的所有 PLHIV，这些患者在 2019 年至 2021 年期间有记录的 DTG 转换，且在转换日至少有 36 个月的护理。体重变化使用具有转换日期的两点分段线性混合模型进行估计。其次，我们基于观察数据模拟了一系列目标试验（ETT），并进行了汇总逻辑回归分析，以比较转换为 DTG 的 PLHIV 与未转换的 PLHIV 中 SWG 的发生情况。
我们首先纳入了来自布基纳法索、科特迪瓦和尼日利亚的 6705 名 PLHIV。他们在转换时的中位年龄为 48 岁（IQR：42-54），中位随访时间为 9 年（IQR：6-12），63%为女性。大多数患者从依非韦伦（EFV）为基础的 ART（56.6%）和奈韦拉平（NVP）为基础的 ART（30.9%）转换。与转换前的平均体重增加（AWG）每年 0.62 公斤/年（95%CI：0.36-0.88）相比，转换后的 AWG 明显升高，为 3.07 公斤/年（95%CI：2.33-3.80）。与 NVP 为基础的 ART 相比，之前接受 EFV 和蛋白酶抑制剂（PI）为基础的 ART 的患者的转换后 AWG 更大。包括 9598 人/试验的 24 个 ETT 的序列汇总逻辑回归分析表明，转换为 DTG 与 SWG 显著相关（优势比[aOR]=2.54；95%CI=2.18-2.97）。
在西非，12 个月的 DTG 暴露与体重显著增加有关，特别是在之前接受 EFV 和 PI 为基础的 ART 的 PLHIV 中。在 HIV 队列中，需要持续进行体重监测和代谢特征分析，以明确 DTG 的长期心血管代谢影响，因为患有或存在心血管疾病风险的患者可能会从替代的 ART 方案中获益。
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