Department of Medicine, Division of Infectious Diseases, Northwestern University, Chicago, IL.
Department of Internal Medicine, Section of Geriatric Medicine Rush University Medical Center, Chicago, IL.
J Acquir Immune Defic Syndr. 2022 Feb 1;89(Suppl 1):S34-S46. doi: 10.1097/QAI.0000000000002858.
The ability of virally suppressive antiretroviral therapy use to extend the life span of people with HIV (PWH) implies that the age of PWH will also increase. Among PWH, extended survival comes at a cost of earlier onset and increased rates of aging-associated comorbidities and geriatric syndromes, with persistent inflammation and immune dysregulation consequent to chronic HIV infection and to antiretroviral therapy use contributing to an overall decrease in health span. The geroscience hypothesis proposes that the root causes of most aging-related chronic diseases and conditions is the aging process itself. Hence, therapeutically targeting fundamental aging processes could have a greater impact on alleviating or delaying aging-associated comorbidities than addressing each disease individually. Extending the geroscience hypothesis to PWH, we speculate that targeting basic mechanisms of aging will improve overall health with age. Clinical features and pathophysiologic mechanisms of chronic diseases in PWH qualitatively resemble those seen in older adults without HIV. Therefore, drugs that target any of the pillars of aging, including metformin, rapamycin, and nicotinamide adenine dinucleotide precursors, may also slow the rate of onset of age-associated comorbidities and geriatric syndromes in PWH. Drugs that selectively induce apoptosis of senescent cells, termed senolytics, may also improve health span among PWH. Preliminary evidence suggests that senescent cell burden is increased in PWH, implying that senescent cells are an excellent therapeutic target for extending health span. Recently initiated clinical trials evaluating senolytics in age-related diseases offer insights into the design and potential implementation of similar trials for PWH.
抗逆转录病毒疗法抑制病毒的能力可以延长 HIV 感染者（PWH）的寿命，这意味着 PWH 的年龄也将增加。在 PWH 中，延长生存是以提前发病和增加与衰老相关的合并症和老年综合征的发生率为代价的，持续的炎症和免疫失调是由于慢性 HIV 感染和抗逆转录病毒治疗的使用，导致健康寿命总体缩短。衰老科学假说提出，大多数与衰老相关的慢性疾病和状况的根本原因是衰老过程本身。因此，针对基本衰老过程进行治疗可能比单独治疗每种疾病对缓解或延迟与衰老相关的合并症产生更大的影响。将衰老科学假说扩展到 PWH，我们推测针对衰老的基本机制将改善随年龄增长的整体健康状况。PWH 中慢性疾病的临床特征和病理生理机制在质上与没有 HIV 的老年人相似。因此，靶向衰老的任何支柱的药物，包括二甲双胍、雷帕霉素和烟酰胺腺嘌呤二核苷酸前体，也可能减缓 PWH 中与年龄相关的合并症和老年综合征的发病速度。选择性诱导衰老细胞凋亡的药物，称为衰老细胞清除剂，也可能改善 PWH 的健康寿命。初步证据表明，PWH 中衰老细胞负担增加，这意味着衰老细胞是延长健康寿命的一个极好的治疗靶点。最近启动的评估衰老细胞清除剂在与年龄相关的疾病中的临床试验为设计和潜在实施针对 PWH 的类似试验提供了思路。
