Chatterjee Aditi, Matsangos Aerielle, Latinovic Olga S, Heredia Alonso, Silvestri Giovannino
Department of Medicine, School of Medicine, University of Maryland, MD, 21201, USA.
Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, 21201, USA.
Arch Stem Cell Ther. 2024;5(1):5-13. doi: 10.46439/stemcell.5.020.
Human immunodeficiency virus type 1 (HIV-1) continues to pose a significant global health challenge despite advances in combined antiretroviral therapy (cART), which has transformed HIV-1 infection from a fatal disease to a manageable chronic condition. However, cART is not curative, and its long-term use is associated with challenges such as pill burden, drug toxicities, and the emergence of drug-resistant viral strains. The persistence of active viral reservoirs necessitates lifelong treatment, highlighting the need for alternative therapeutic strategies capable of achieving HIV-1 remission or cure. Stem cell therapy has emerged as a promising approach to address these challenges by targeting latent viral reservoirs, restoring host immune function, and potentially achieving sustained viral suppression in the absence of cART. This review critically evaluates current scientific literature on stem cell therapies for HIV-1, focusing on three major approaches: , . Each approach is examined in terms of its underlying mechanisms, clinical feasibility, recent advancements, and associated challenges. Furthermore, future research directions are discussed, emphasizing the optimization of the current treatment protocols, enhancement of safety and efficacy, and the importance of large-scale clinical trials with different cohorts (different HIV clades, different genders of participants, and pediatric HIV) to evaluate long-term outcomes that include effective and scalable HIV cure challenges. Collaborative efforts across multidisciplinary fields are needed to overcome existing barriers so to realize the full therapeutic potential of stem cell-based approaches for developing an effective and scalable remission or cure strategies.
尽管联合抗逆转录病毒疗法（cART）取得了进展，将1型人类免疫缺陷病毒（HIV-1）感染从一种致命疾病转变为一种可控制的慢性病，但HIV-1仍然是一项重大的全球健康挑战。然而，cART并非治愈性疗法，其长期使用伴随着诸多挑战，如服药负担、药物毒性以及耐药病毒株的出现。活跃病毒库的持续存在使得终身治疗成为必要，这凸显了需要能够实现HIV-1缓解或治愈的替代治疗策略。干细胞疗法已成为一种有前景的方法，通过靶向潜伏病毒库、恢复宿主免疫功能以及在不使用cART的情况下潜在地实现持续病毒抑制来应对这些挑战。本综述批判性地评估了当前关于HIV-1干细胞疗法的科学文献，重点关注三种主要方法： ， 。每种方法都从其潜在机制、临床可行性、近期进展以及相关挑战等方面进行了审视。此外，还讨论了未来的研究方向，强调了优化当前治疗方案、提高安全性和疗效的重要性，以及开展针对不同队列（不同HIV分支、不同性别参与者以及儿科HIV）的大规模临床试验以评估包括有效且可扩展的HIV治愈挑战在内的长期结果的重要性。需要跨多学科领域的协作努力来克服现有障碍，从而实现基于干细胞方法在开发有效且可扩展的缓解或治愈策略方面的全部治疗潜力。
