PDF(Pubmed)
Abstract：
Dolutegravir is an integrase inhibitor and is recommended by the World Health Organization as the preferred first-line and second-line human immunodeficiency virus treatment in all populations. Excessive weight gain associated with dolutegravir-based regimens is an emerging issue; however, the long-term metabolic consequences of this effect have not been fully understood. Growing evidence shows that this leads to a higher incidence of hyperglycemia, hypertension, and metabolic syndrome, along with elevated cardiovascular risk. Dolutegravir-based regimens, also associated with greater adipocyte differentiation and greater expression of markers associated with lipid storage, continue to be a problem among patients living with human immunodeficiency virus. The mechanisms by which certain antiretroviral therapy agents differentially contribute to weight gain remain unknown. Some clinical investigators speculate that dolutegravir could interfere with central nervous system appetite regulation (melanocortin-4 receptor) and insulin signaling, or may have better penetration of adipose tissue where they could exert a direct impact on adipose tissue adipogenesis, fibrosis, and insulin resistance. This review summarizes our current understanding of weight gain and fat changes associated with dolutegravir and its possible secondary metabolic comorbidities.
摘要：
Dolutegravir是一种整合酶抑制剂，被世界卫生组织推荐为所有人群中首选的一线和二线人类免疫缺陷病毒治疗方法。与基于dolutegravir的方案相关的体重增加过多是一个新出现的问题;然而，这种效应的长期代谢后果还没有被完全理解。越来越多的证据表明，这导致高血糖的发生率更高，高血压,代谢综合征,以及心血管风险升高。基于Dolutegravir的方案，也与更大的脂肪细胞分化和更高的表达与脂质储存相关的标志物有关，仍然是人类免疫缺陷病毒患者的一个问题。某些抗逆转录病毒疗法对体重增加有差异的机制仍然未知。一些临床研究人员推测，dolutegravir可能会干扰中枢神经系统食欲调节（黑皮质素-4受体）和胰岛素信号，或者可能对脂肪组织有更好的渗透，它们可以对脂肪组织的脂肪生成产生直接影响，纤维化，和胰岛素抵抗。这篇综述总结了我们目前对与dolutegravir及其可能的继发性代谢合并症相关的体重增加和脂肪变化的理解。
