Weight gain stopping/switch rules for antiretroviral clinical trials.
Weight gain stopping/switch rules for antiretroviral clinical trials.
复制标题
抗逆转录病毒临床试验的体重增加停止/转换规则。
DOI：
10.1097/qad.0000000000003221
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Manasa,Justen
中科院分区：
文献类型：
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作者：
Kouamou,Vinie;Inzaule,Seth;Manasa,Justen
基于多替拉韦的治疗方案正在非洲推广，预计到 2022 年底，中低收入国家 90% 以上的艾滋病毒感染者 (PHIV) 将采用该治疗方案 [1, 2]。尽管迄今为止报道多替拉韦具有高效能[1, 3]，但人们对随后的体重增加和相关代谢并发症的担忧已经出现。研究结果显示，在非洲进行的临床试验中，与依非韦伦治疗相比，接受多替拉韦治疗的患者体重增加更多：导致人们担心终身抗逆转录病毒治疗 (ART) 会导致肥胖的长期影响[4, 5]。此外，最近的研究 (2021) 报告了 PHIV 患者中体重增加与多替拉韦之间的关联，最常见于黑人群体和女性 [6, 7]。尽管多替拉韦导致体重增加的机制尚不清楚；据推测，体重增加本质上可能是多因素造成的：遗传倾向、艾滋病毒相关因素、“恢复健康”体重增加和人口因素都起作用。非洲多替拉韦的临床和规划经验正在逐步增加。Venter 等人[8]在他们最近的文章中讨论了与多替拉韦和体重增加相关的因素，并提出了临床试验设计中体重增加和代谢监测的初步指导，包括临床肥胖患者停止/转换治疗的规则。尽管这些指南在试验环境中监测体重增加和代谢紊乱方面凭经验发挥作用，但它们也可以在常规临床护理中发挥作用，特别是在临床肥胖患者中。尽管仍需要更多数据来了解 ART 引起的体重增加的影响及其背后的机制，但仍需要监测和解决常规护理环境中出现的严重临床体重增加。然而，由于资源有限的环境中监测系统薄弱，密切的药物警戒可能是一个挑战。例如，在这些环境中，监测一些建议的参数（如 HbA1c、双能 X 射线吸收测定法、饮食或生活方式数据）可能是一个挑战。 Lamorde 等人最近的一项研究[9]例如，在乌干达，记录并描述了 PHIV 患者在多替拉韦过渡后出现高血糖的情况；作者强调了在药物警戒系统薄弱的环境中及早发现与 ART 相关的严重毒性的重要性。
Dolutegravir-based regimens is being scaled-up in Africa and it is anticipated that> 90% of people with HIV (PHIV) in low-and-middle income countries will be on this regimen by end of 2022 [1, 2]. Despite the high efficacy of dolutegravir reported so far [1, 3], concerns about subsequent weight gain and related metabolic complications have emerged. Findings reported greater weight gain in patients treated with dolutegravir compared to efavirenz in clinical trials in Africa: leading to concerns about long-term effects of obesity with lifelong antiretroviral therapy (ART)[4, 5]. Furthermore, recent studies (2021) have reported an association between weight gain and dolutegravir in PHIV, most often in Black ethnic groups and women [6, 7]. Although the mechanisms whereby dolutegravir cause weight gain remain unclear; it is hypothesized that the weight gain may be multifactorial in nature: with genetic predisposition, HIV-related factors, the ‘return to health’weight gain and demographic factors all contributing. Clinical and programmatic experience with dolutegravir in Africa is progressively increasing.Venter et al.[8] in their recent article discussed the factors associated with dolutegravir and weight gain, and proposed the preliminary guidance for weight gain and metabolic monitoring in clinical trial design including rules for stopping/switching treatment for those with clinical obesity. Although these guidelines would empirically play a role in the monitoring of weight gain and metabolic disorders in trial settings, they also could play a role in routine clinical care especially among patients with clinical obesity. Although more data is still needed to understand the impact of ART induced weight gain and the mechanism behind it, there is still a need to monitor and address severe clinical weight gain as they emerge in routine care settings. However, close pharmacovigilance could be a challenge owing to weak monitoring systems in resource limited settings. For example, monitoring of some of the proposed parameters like HbA1c, dual-energy X-ray absorptiometry, dietary or lifestyle data could be a challenge in these settings. A recent study by Lamorde et al.[9] in Uganda, for example, documented and characterized hyperglycaemia in PHIV following dolutegravir transition; the authors emphasized the importance of early detection of serious toxicities associated with ART in settings where pharmacovigilance systems are weak.