Immune checkpoint blockade in HIV.

Area of Science:

• Immunology
• Virology
• Therapeutics

Background:

• Antiretroviral therapy (ART) significantly enhances life expectancy for people with HIV (PWH) but is not curative, requiring lifelong adherence.
• Chronic HIV infection leads to immune exhaustion, characterized by persistent elevated immune checkpoint expression, even during ART.
• Immune checkpoints negatively regulate T cell signaling, contributing to impaired immune responses in HIV.

Purpose of the Study:

• To review the role of immune checkpoints in persistent HIV infection.
• To discuss the potential of immune checkpoint blockade (ICB) as a therapeutic strategy for HIV cure or remission.
• To explore ICB's ability to reverse HIV latency and restore HIV-specific T cell function.

Main Methods:

• Literature review of recent evidence on immune checkpoints in HIV.
• Analysis of the impact of immune exhaustion on T cell function during chronic HIV infection.
• Exploration of therapeutic strategies targeting immune checkpoints for HIV persistence.

Main Results:

• Elevated immune checkpoints contribute to T cell exhaustion in PWH, persisting even with ART.
• Immune checkpoint blockade has shown success in cancer therapy by augmenting anti-tumor T cell responses.
• ICB presents a potential strategy to overcome T cell exhaustion in HIV.

Conclusions:

• Reversing T cell exhaustion via ICB could be crucial for achieving long-term HIV control or remission.
• Targeting immune checkpoints may offer a novel therapeutic avenue to address HIV persistence on ART.
• Further research into ICB is warranted to explore its efficacy in HIV cure strategies.