Understanding the HIV-specific T-cell response to immune checkpoint blockade: what can we learn from cancer...

This review examines the potential of immune checkpoint blockade (ICB) to enhance HIV-specific T-cell responses, leveraging insights from cancer immunotherapy to tackle persistent challenges in achieving long-term potent immune response to keep the virus in check. By highlighting lessons from oncology, we aim to discuss innovative strategies to improve HIV treatment outcomes and advance the search for a functional cure.

ICB extends beyond targeting PD-1 and CTLA-4, with novel therapies and engineered approaches in cancer also holding promise for HIV treatment. HIV-specific T-cell exhaustion, stemness, T-cell receptor clonal replacement, and antigen load critically influence ICB success, emphasizing the complexity and need for research on innovative strategies that can further enhance treatment efficacy in the context of HIV.

While ICB shows promising potential, its role in HIV cure strategies requires further exploration in clinical trials with people with HIV (PWH). Future research should focus on advancing ICB as a tool for durable HIV control by investigating novel immune checkpoint targets, bispecific antibodies, minimizing toxicity, and identifying biomarkers for effective ICB responses.