Pharmacogenomic strategies and CRISPR-CAS9 Gene Editing: A targeted approach towards HIV cure

HIV/AIDS remains one of the most pressing global health challenges, affecting nearly 39.9 million people worldwide in 2023 alone. Despite the success of antiretroviral therapy (ART) in controlling viral replication and improving patient survival, a complete cure remains out of reach due to the persistence of latent HIV reservoirs. These reservoirs, consisting primarily of resting CD4+ T cells and macrophages, are sequestered in anatomical sanctuary sites such as the brain and lymphoid tissues, where current therapies cannot reach or eradicate the virus. Recent advancements in geneediting technologies, particularly CRISPR/Cas9, have opened new possibilities for targeting and excising integrated HIV-1 proviral DNA directly from infected cells. Experimental studies have shown that CRISPR/Cas9 can effectively disrupt viral gene sequences, including those hidden within latent reservoirs. However, therapeutic application still faces challenges—one of the most critical being the formation of episomal circular DNA with reformed long terminal repeats (LTRs) after excision. These episomes may remain transcriptionally active, contributing to potential viral rebound. To address this, ongoing research is focused on developing combinatorial strategies that employ multiple guide RNAs (gRNAs) targeting different regions of the HIV genome. This approach aims to reduce the risk of viral escape and enhance editing precision. Additionally, integrating pharmacogenomic insights into treatment planning allows for more personalized and effective intervention by considering individual genetic variability in drug metabolism and response. Combining gene-editing tools with pharmacogenomic strategies represents a promising shift toward a functional or even sterilizing cure for HIV. Continued investigation and refinement are essential to overcome current barriers and move closer to eradicating the virus.