Immuno-Engineering of Hematopoietic Stem Cells for Durable Immune Resistance to HIV: From the CCR5Δ32 Mutation to Autologous Gene Therapies Mediated by Lentiviral Vectors

Rare cases of sustained HIV remission following hematopoietic stem cell transplantation have demonstrated that durable,systemic resistance to HIV is a biological possibility. These exceptional outcomes have fundamentally reframed the cure agenda, establishing a new paradigm: the host immune system can be engineered for intrinsic resistance. This review examines the immuno-engineering of hematopoietic stem cells (HSCs) as a foundational strategy to reconstitute a permanently HIV-resistant immune system. I trace the conceptual evolution from the protective CCR5Δ32 mutation to modern autologous therapies using lentiviral vectors and genome-editing technologies. I critically analyze the biological rationale, technological platforms, clinical progress, and translational challenges of HSC-based resistance, positioning engineered immunity as the cornerstone of a durable, one-time curative intervention.