Advancing precision medicine in immune checkpoint blockade for HIV/AIDS: Current strategies and future directions.

Abstract

Acquired immunodeficiency syndrome (AIDS)/human immunodeficiency virus (HIV) patients experience significant increase in their survival and decline in the mortality with the advent of antiretroviral therapy (ART). Nonetheless, ART alone still cannot completely cure AIDS/HIV patients. Furthermore, the virus remains latent in resting CD4+T cells for extended periods, posing a continuous threat to AIDS/HIV patients. Immune checkpoint blockades (ICBs), as a promising immunotherapy, inaugurate new pathways for AIDS/HIV cure or remission given their capability to break down the latency limit of HIV, and promote the regeneration and activation of HIV-specific T cells. However, not all AIDS/HIV patients respond to immune checkpoint inhibitors (ICIs), similar to that encountered in cancer patients, accompanied by the risk of severe immune-related adverse events (irAEs) in some cases. Accordingly, the present study was conducted to explore the possibility of personalized medicine tailored to the host discrepancy, with purposes of achieving better treatment outcomes, higher objective response rates, and fewer irAEs. Strategies for ICIs based on individual differences are documented to be conducive to improving therapeutic outcomes for patients. Therefore, this study intended to improving the therapeutic efficacy of ICIs in AIDS/HIV patients within the context of precision immunotherapy, including monotherapy and combination strategies, as well as the application of predictive biomarkers.