CAR-T Cell Therapy for HIV Cure: Current Challenges, Advances and Future Directions.

Area of Science:

• Immunology
• Virology
• Cell Therapy

Background:

• Antiretroviral therapy (ART) suppresses HIV but cannot eliminate latent reservoirs, causing viral rebound upon treatment cessation.
• Latent HIV reservoirs are a major barrier to achieving a functional cure for HIV infection.

Purpose of the Study:

• To systematically review and analyze the current evidence on CAR T-cell therapy for HIV eradication.
• To assess the potential of CAR T-cell therapy as a strategy for achieving durable HIV remission.

Main Methods:

• A systematic PubMed search was conducted from July 2020 to June 2025, identifying 253 studies.
• Seventy-four studies met the inclusion criteria and underwent qualitative analysis, including preclinical and early clinical data.

Main Results:

• Preclinical data indicate CAR T-cells can target and eliminate HIV-infected cells and reservoirs, with long-term persistence observed.
• Dual-target CAR T-cell designs and combination therapies (e.g., with checkpoint inhibitors or latency-reversing agents) enhanced efficacy.
• Early clinical trials demonstrated the safety of CAR T-cell therapy and showed modest reductions in HIV reservoirs.

Conclusions:

• CAR T-cell therapy is a promising approach for a functional HIV cure, offering a potential strategy to overcome ART limitations.
• Further optimization of CAR T-cell design, integration with gene-editing technologies, and robust clinical evaluation are crucial for confirming long-term efficacy and safety.