HIV cure: from early therapies to cutting-edge strategies

Abstract HIV has challenged humanity for decades, quietly establishing latent reservoirs that evade even the most potent antiretroviral therapies (ART). While ART transformed HIV from a fatal disease into a manageable condition, the virus’s hidden persistence continues to fuel the global epidemic. This review narrates the story of HIV treatment, tracing the evolution of therapeutic strategies from conventional ART to innovative gene-editing and immunotherapeutic approaches. Central to this journey is the CRISPR-Cas system, a molecular scalpel that has enabled precise excision of integrated proviral DNA, disruption of entry co-receptors like CCR5, and modulation of host restriction factors to bolster innate defenses. Preclinical studies reveal that CRISPR interventions can reduce viral reservoirs, prevent reactivation, and restore antiviral immunity, offering a glimpse of a future beyond lifelong ART. Challenges remain, notably efficient delivery to infected cells and minimizing off-target effects, but advances in vector design and computational prediction tools are steadily overcoming these barriers. By weaving experimental findings with translational perspectives, this review highlights CRISPR’s potential to provide durable, scalable, and cost-effective HIV control, particularly in low-resource settings. Ultimately, this narrative underscores a hopeful vision: that precise gene editing may transform HIV therapy from lifelong suppression into a pathway toward functional cure, changing the story of the virus and the lives it touches.