Advancing towards HIV-1 remission: Insights and innovations in stem cell therapies

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: <i>1) hematopoietic stem cell transplantation (HSCT)</i>, <i>2) gene therapy, and 3) cell-based immunotherapies</i>. 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.