Navigating the Roadblocks: Progress and Challenges in Cell-Based Therapies for Human Immunodeficiency Virus

Cell-based therapies represent a major advancement in the treatment and management of HIV/AIDS, with a goal to overcome the limitations of traditional antiretroviral therapy (ART). These innovative approaches not only promise a functional cure by reconstructing the immune landscape but also address the persistent viral reservoirs. For example, stem cell therapies have emerged from the foundational success of allogeneic hematopoietic stem cell transplantation in curing HIV infection in a limited number of cases. B cell therapies make use of genetically modified B cells constitutively expressing broadly neutralizing antibodies (bNAbs) against target viral particles and infected cells. Adoptive cell transfer (ACT), including TCR-T therapy, CAR-T cells, NK-CAR cells, and DC-based therapy, is adapted from cancer immunotherapy and repurposed for HIV eradication. In this review, we summarize the mechanisms through which these engineered cells recognize and destroy HIV-infected cells, the modification strategies, and their role in sustaining remission in the absence of ART. The review also addresses the challenges to cell-based therapies against HIV and discusses the recent advancements aimed at overcoming them.