HIV Persistence, Latency, and Cure Approaches: Where Are We Now? Tessa C. Chou, Nishad S. Maggirwar, and Matthew D. Marsden review the current state of HIV research, focusing on the challenges of eliminating the latent viral reservoir, which remains a major obstacle to curing HIV infection. Antiretroviral therapy (ART) effectively suppresses active HIV replication but cannot target latently infected cells, which can lead to viral rebound if ART is stopped. The latent reservoir, primarily found in CD4+ T cells, persists despite long-term ART, making it a critical target for cure strategies. Current research explores various approaches to eliminate this reservoir, including latency reversal agents (LRAs) that reactivate latent HIV, followed by immune-mediated elimination of infected cells. Other strategies involve gene therapy, stem cell transplantation, and the use of broadly neutralizing antibodies. Animal models, such as non-human primates and humanized mice, are essential for studying HIV latency and testing cure approaches. Despite significant progress, challenges remain in effectively targeting and eliminating the latent reservoir, highlighting the need for further research to develop safe and scalable HIV cure methods.HIV Persistence, Latency, and Cure Approaches: Where Are We Now? Tessa C. Chou, Nishad S. Maggirwar, and Matthew D. Marsden review the current state of HIV research, focusing on the challenges of eliminating the latent viral reservoir, which remains a major obstacle to curing HIV infection. Antiretroviral therapy (ART) effectively suppresses active HIV replication but cannot target latently infected cells, which can lead to viral rebound if ART is stopped. The latent reservoir, primarily found in CD4+ T cells, persists despite long-term ART, making it a critical target for cure strategies. Current research explores various approaches to eliminate this reservoir, including latency reversal agents (LRAs) that reactivate latent HIV, followed by immune-mediated elimination of infected cells. Other strategies involve gene therapy, stem cell transplantation, and the use of broadly neutralizing antibodies. Animal models, such as non-human primates and humanized mice, are essential for studying HIV latency and testing cure approaches. Despite significant progress, challenges remain in effectively targeting and eliminating the latent reservoir, highlighting the need for further research to develop safe and scalable HIV cure methods.