Genomic frontiers in HIV research: from pathogenesis to curative strategies

Abstract Background Human immunodeficiency virus (HIV) has been one of the most significant global health challenges since its discovery in the early 1980s. Classified as a lentivirus, HIV integrates into the host genome, leading to chronic immune dysfunction and the establishment of latent viral reservoirs. Despite the efficacy of antiretroviral therapy (ART) in controlling viral replication, a complete cure remains elusive due to the virus’s ability to mutate, evade immune responses, and persist in latent reservoirs. Purpose This review aims to provide a comprehensive overview of how genomic technologies have transformed our understanding of HIV pathogenesis, replication, and latency. Additionally, it explores novel therapeutic strategies that target both viral and host genomic factors, offering potential avenues for a curative approach to HIV. Main body Genomic technologies such as next-generation sequencing (NGS), CRISPR gene editing, and RNA sequencing (RNA-seq) have provided critical insights into HIV biology. These tools have elucidated the HIV genome, identifying viral and host factors critical for replication and latency. Advances in proteomics have revealed the interactions between viral proteins and host machinery, contributing to the development of targeted therapies. Therapeutic strategies, including RNA-based therapies and CRISPR-Cas9-mediated gene editing, demonstrate promising preclinical results in silencing viral gene expression or excising proviral DNA, though translation to clinical applications faces substantial challenges. However, significant obstacles in delivery mechanisms and safety concerns regarding off-target effects remain formidable hurdles. The persistence of latent reservoirs, which evade current ART, continues to be the primary barrier to achieve a cure. Conclusion The integration of genomics into HIV research has opened new therapeutic avenues, offering hope for a functional or complete cure. However, further research is needed to overcome delivery challenges, target latent reservoirs effectively, and ensure the safety of gene-editing technologies. Graphical abstract