PDF(Pubmed)
Abstract：
Dolutegravir (DTG), an integrase strand transfer inhibitor is currently the recommended first and second line anti-retroviral therapy (ART) anchor agent by the World Health Organization due to its favorable side effect profile, high efficacy and genetic barrier to resistance.Despite its very good side effect profile, there have been multiple case reports of ART experienced patients developing hyperglycemia within weeks to a few months after switching to DTG preceded by weight loss. At population level, however, DTG as well as other integrase inhibitors have been demonstrated to have a reduced risk of incident diabetes mellitus (T2DM) compared to other HIV drug classes.Following multiple similar reports of accelerated hyperglycemia in Uganda during the first pilot year of DTG use, the Uganda Ministry of Health recommended withholding dolutegravir in all patients who develop diabetes. Whether this recommendation should be applied to all patients with incident T2DM remains to be demonstrated.We present a clinical case of an HIV positive ART naïve man who was diagnosed with T2DM after 36 weeks on DTG. We describe changes in blood glucose, glycated hemoglobin, insulin resistance and pancreatic beta cell function before and after withholding DTG. We demonstrated that he was phenotypically different from the reported cases of accelerated hyperglycemia and he continued to have worsening insulin resistance despite withholding DTG. His blood glucose improved with dietary T2DM management. It is possible he had an inherent risk of developing T2DM independent of his exposure to DTG. This put in question whether DTG should universally be withheld in PLHIV with incident T2DM in Uganda.
摘要：
Dolutegravir(DTG),整合酶链转移抑制剂是目前世界卫生组织推荐的一线和二线抗逆转录病毒疗法（ART）锚定剂，由于其有利的副作用，高功效和遗传屏障的抗性。尽管它的副作用非常好，已有多例病例报告称,ART患者在转用DTG后几周至几个月内出现高血糖,随后体重减轻.在人口层面，然而,与其他HIV药物类别相比，DTG以及其他整合酶抑制剂已被证明具有降低的偶发糖尿病（T2DM）风险。在使用DTG的第一个试验年期间，乌干达有多个类似的高血糖加速报告，乌干达卫生部建议在所有糖尿病患者中停用dolutegravir.该建议是否适用于所有2型糖尿病患者仍有待证实。我们介绍了一名HIV阳性ART初治男子的临床病例，该男子在DTG治疗36周后被诊断为T2DM。我们描述了血糖的变化，糖化血红蛋白,停用DTG前后的胰岛素抵抗和胰岛β细胞功能。我们证明他在表型上与报告的加速高血糖病例不同，尽管保留了DTG，但他的胰岛素抵抗仍在恶化。通过饮食管理T2DM，他的血糖得到改善。他可能有发展为T2DM的固有风险，而与他暴露于DTG无关。这引起了疑问，是否应在乌干达发生T2DM的PLHIV中普遍保留DTG。
