Abstract

Human immunodeficiency virus (HIV) infection remains a global health challenge, with more than 38 million 
individuals living with the virus worldwide in 2023. Despite antiretroviral therapy (ART) effectively suppressing 
viral replication, latent reservoirs of integrated proviral DNA prevent eradication and necessitate lifelong treatment. 
This review examined CRISPR-Cas gene editing technologies as promising strategies for eliminating latent HIV 
reservoirs and achieving functional cure outcomes. This review synthesized peer-reviewed studies from PubMed, 
Web of Science, and Scopus (2015–2025), focusing on in vitro, in vivo, and preclinical reports that evaluate CRISPR
Cas applications against HIV latency and persistence. CRISPR-Cas9 and next-generation Cas systems have 
demonstrated efficient cleavage of proviral DNA, excision of integrated genomes, and disruption of essential viral 
genes. In preclinical studies, Cas9-guided strategies achieved up to 90% reduction of integrated HIV DNA in latently 
infected cells. Emerging innovations included base and prime editing for precise nucleotide modifications, multiplex 
targeting to prevent viral escape, and delivery systems using adeno-associated virus (AAV) and lipid nanoparticles. 
Combination strategies that pair CRISPR editing with latency-reversing agents (LRAs) or immune-enhancing 
modalities have shown synergistic effects in clearing reservoirs in animal models. CRISPR-Cas gene editing 
provided a rational and increasingly feasible approach to functional HIV cure strategies. Key challenges remained in 
delivery specificity, off-target effects, and immune safety. Translational progress will require carefully designed 
clinical trials integrating CRISPR with existing and novel therapeutic paradigms. 
Keywords: CRISPR-Cas, HIV reservoirs, Functional cure, Gene editing, Latency.