Eliminating the HIV tissue reservoir: current strategies and challenges

Abstract

Background

Acquired immunodeficiency syndrome (AIDS) is still one of the most widespread and harmful infectious diseases in the world. The presence of reservoirs housing the human immunodeficiency virus (HIV) represents a significant impediment to the development of clinically applicable treatments on a large scale. The viral load in the blood can be effectively reduced to undetectable levels through antiretroviral therapy (ART), and a higher concentration of HIV is sequestered in various tissues throughout the body, forming the tissue reservoir - the source of viremia after interruption treatment.

Methods

We take the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) as a guideline for this review. In June 2023, we used the Pubmed, Embase, and Scopus databases to search the relevant literature published in the last decade.

Results

Here we review the current strategies and treatments for eliminating the HIV tissue reservoirs: early and intensive therapy, gene therapy (including ribozyme, RNA interference, RNA aptamer, zinc finger enzyme, transcriptional activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats/associated nuclease 9 (CRISPR/Cas9)), ‘Shock and Kill’, ‘Block and lock’, immunotherapy (including therapeutic vaccines, broadly neutralising antibodies (bNAbs), chimeric antigen receptor T-cell immunotherapy (CAR-T)), and haematopoietic stem cell transplantation (HSCT).

Conclusion

The existence of an HIV reservoir is the main obstacle to the complete cure of AIDS. Choosing the appropriate strategy to deplete the HIV reservoir and achieve a functional cure for AIDS is the focus and difficulty of current research. So far, there has been a lot of research and progress in reducing the HIV reservoir, but in general, the current research is still very preliminary. Much research is still needed to properly assess the reliability, effectiveness, and necessity of these strategies.

Keywords:

• HIV
• reservoir
• strategy
• treatment
• gene therapy
• immunotherapy

Disclosure statement

No potential conflict of interest was reported by the authors.