Abstract

Despite sustained viral suppression achieved through antiretroviral therapy (ART), HIV persists in latently infected 
cells, forming proviral reservoirs that remain the principal barrier to cure. Latency reversing agents (LRAs) and 
CRISPR-Cas9 gene editing are the two innovative approaches that have emerged as leading strategies for targeting 
and eliminating these reservoirs in ART-suppressed individuals. While LRAs aimed to reactivate latent proviruses 
for immune-mediated clearance, CRISPR-Cas9 seeks to excise or inactivate integrated viral DNA through sequence
specific genome editing. This review aimed to critically compare the efficacy, mechanisms, clinical readiness, and 
safety profiles of these two approaches in the context of HIV proviral elimination. A narrative review methodology 
was employed to synthesize peer-reviewed findings from preclinical and clinical studies published between 2010 and 
2025. Findings revealed that LRAs consistently induced HIV transcription but failed to significantly reduce 
reservoir size due to limited immune clearance, whereas CRISPR-Cas9 demonstrated more definitive proviral 
disruption in preclinical models but is constrained by delivery challenges and the risk of viral escape or off-target 
effects. Both strategies hold promise, neither is sufficient alone; combination therapies, improved delivery systems, 
and individualized viral targeting may be necessary to achieve durable remission or eradication. Future research 
should prioritize integrated cure strategies combining molecular precision with immune enhancement. 
Keywords: HIV cure strategies, CRISPR-Cas9 gene editing, Latency reversing agents, Proviral elimination, ART
suppressed individuals.