Khurana Vansh, Radu Rodica, Feinstein Matthew J, Apetrei Cristian, Pandrea Ivona
Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States.
Internal Medicine Department, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania.
Front Cell Infect Microbiol. 2025 Apr 22;15:1556315. doi: 10.3389/fcimb.2025.1556315. eCollection 2025.
With the advent of antiretroviral therapy (ART) that effectively suppresses HIV replication, and reduced AIDS progression, the clinical spectrum of HIV infection has dramatically changed. Currently, the people living with HIV (PLWH) who receive ART have a nearly normal prognostic of survival, yet they still experience higher morbidity and mortality than age-matched uninfected subjects. The higher risk of death in PLWH is linked to persistence of residual systemic inflammation and T-cell activation. These factors contribute to accelerated aging and higher incidence of HIV-associated non-AIDS conditions, thereby presenting new diagnostic and therapeutic challenges. This new shifting paradigm of HIV infection associates a higher incidence of cardiovascular disease (CVD), such as stroke, acute myocardial infarction and sudden cardiac death, in stark contrast to the reduced incidence of opportunistic infections. The incidence of acute myocardial infarction and coronary disease is several folds higher in PLWH than in the general population. Study of United States (US) death certificates listing HIV infection shows that the deaths from CVD doubled between 1996 and 2006. CVD will become an even more prominent comorbidity considering that more than 50% of PLWH in the US are over 50 years old, an age that more frequently associates CVD, and cardiovascular complications are more frequent in urban African-Americans and Hispanics, which are disproportionately affected by HIV. Therefore, reducing the overall risk of these complications will become the primary challenge in the management of chronic HIV infection. Not surprisingly, the REPRIEVE trial showed a substantial benefit of statins to PLWH, and the current guidelines include statin administration to PLWH. Nonhuman primate (NHP) models for the cardiovascular comorbidities associated with HIV are currently available and their use for testing new therapeutic approaches aimed at countering the effects of hypercoagulability and CVD is discussed. Their use can be of tremendous help to understand the etiology, pathophysiology, and the determinants of CVD in PLWH, which are currently poorly understood. Use of the NHP models could help in dissecting the relative contribution of the virus, behavioral factors, and ART to cardiovascular risk, having the potential to help us establish new strategic approaches aimed at controlling HIV-related CVD.
随着有效抑制HIV复制的抗逆转录病毒疗法（ART）的出现以及艾滋病进展的减缓，HIV感染的临床谱发生了巨大变化。目前，接受ART治疗的HIV感染者（PLWH）的生存预后几乎正常，但他们的发病率和死亡率仍高于年龄匹配的未感染人群。PLWH较高的死亡风险与残余全身炎症和T细胞活化的持续存在有关。这些因素导致加速衰老和HIV相关非艾滋病疾病的更高发病率，从而带来了新的诊断和治疗挑战。与机会性感染发病率降低形成鲜明对比的是，HIV感染的这种新的转变模式与心血管疾病（CVD）的更高发病率相关，如中风、急性心肌梗死和心源性猝死。PLWH中急性心肌梗死和冠心病的发病率比普通人群高几倍。对列出HIV感染情况的美国死亡证明的研究表明，1996年至2006年间，CVD导致的死亡人数增加了一倍。考虑到美国超过50%的PLWH年龄在50岁以上，而这个年龄段CVD更为常见，并且城市非裔美国人和西班牙裔受HIV影响的比例过高，心血管并发症更为频繁，因此CVD将成为一种更为突出的合并症。因此，降低这些并发症的总体风险将成为慢性HIV感染管理的主要挑战。不出所料，REPRIEVE试验显示他汀类药物对PLWH有显著益处，当前指南也将他汀类药物用于PLWH。目前已有与HIV相关的心血管合并症的非人灵长类动物（NHP）模型，并讨论了将其用于测试旨在对抗高凝性和CVD影响的新治疗方法。它们的使用对于理解PLWH中CVD的病因、病理生理学和决定因素有极大帮助，而目前对这些方面了解甚少。使用NHP模型有助于剖析病毒、行为因素和ART对心血管风险的相对贡献，有可能帮助我们建立旨在控制HIV相关CVD的新战略方法。
