Ezintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa.
Medical Practice Evaluation Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115, USA.
J Clin Endocrinol Metab. 2024 Jan 18;109(2):e478-e487. doi: 10.1210/clinem/dgad411.
Rapid advances in the potency, safety, and availability of modern HIV antiretroviral therapy (ART) have yielded a near-normal life expectancy for most people living with HIV (PLWH). Ironically, considering the history of HIV/AIDS (initially called "slim disease" because of associated weight loss), the latest dilemma faced by many people starting HIV therapy is weight gain and obesity, particularly Black people, women, and those who commenced treatment with advanced immunodeficiency. We review the pathophysiology and implications of weight gain among PLWH on ART and discuss why this phenomenon was recognized only recently, despite the availability of effective therapy for nearly 30 years. We comprehensively explore the theories of the causes, from initial speculation that weight gain was simply a return to health for people recovering from wasting to comparative effects of newer regimens vs prior toxic agents, to direct effects of agents on mitochondrial function. We then discuss the implications of weight gain on modern ART, particularly concomitant effects on lipids, glucose metabolism, and inflammatory markers. Finally, we discuss intervention options for PLWH and obesity, from the limitations of switching ART regimens or specific agents within regimens, weight-gain mitigation strategies, and potential hope in access to emerging antiobesity agents, which are yet to be evaluated in this population.
现代 HIV 抗逆转录病毒疗法（ART）在疗效、安全性和可及性方面的快速进步，使大多数 HIV 感染者（PLWH）的预期寿命接近正常。具有讽刺意味的是，考虑到 HIV/AIDS 的历史（最初因其相关的体重减轻而被称为“消瘦病”），许多开始接受 HIV 治疗的人目前面临的最新困境是体重增加和肥胖，尤其是黑人、女性以及那些免疫功能严重受损开始接受治疗的人。我们综述了 PLWH 在接受 ART 治疗时体重增加的病理生理学及其影响，并讨论了尽管近 30 年来已有有效的治疗方法，但为何直到最近才认识到这一现象。我们全面探讨了体重增加的原因理论，从最初的推测，即体重增加仅仅是因从消瘦中恢复而使人们的健康状况得以恢复，到新方案与先前有毒药物的比较效果，再到药物对线粒体功能的直接影响。然后，我们讨论了体重增加对现代 ART 的影响，特别是对血脂、葡萄糖代谢和炎症标志物的伴随影响。最后，我们讨论了 PLWH 和肥胖症的干预选择，包括改变 ART 方案或方案内特定药物的局限性、体重增加缓解策略，以及在这一人群中尚未得到评估的新兴抗肥胖药物的潜在希望。
