Abstract Body

Antiretroviral therapy (ART) has transformed HIV-1 infection from a fatal disease into a manageable chronic condition. However, longitudinal studies reveal that the decay rate of the HIV-1 reservoir is so slow that ART alone cannot eliminate the reservoir within the lifetime of people living with HIV-1 (PLWH). This underscores the urgent need for safe and scalable strategies to achieve an HIV-1 cure. Most HIV-1 cure strategies fall into two main categories: (1) approaches aimed at eradicating or inactivating the reservoir and (2) approaches designed to induce immune-mediated control of the virus. Hematopoietic stem cell transplantation (HSCT) has demonstrated the potential to completely eradicate the HIV-1 reservoir, as seen in case reports of PLWH receiving HSCT for hematologic conditions. However, due to its inherent risks, HSCT is not a feasible cure strategy for otherwise healthy individuals. Consequently, most research has shifted toward strategies focused on immune-mediated control of HIV-1. Cytotoxic CD8+ T cells are strongly associated with spontaneous HIV-1 control, making the enhancement of CD8+ T cell immunity a promising avenue for clearing infected cells and achieving long-term viral suppression. Despite these prospects, therapeutic HIV-1 vaccines have so far failed to produce the desired results in clinical trials. Nevertheless, a range of other compounds – both those specifically designed for HIV-1 cure and repurposed drugs from fields such as oncology and hematology – have been investigated for their potential to impact HIV-1 persistence. While many of these interventions have not succeeded in significantly reducing the reservoir or inducing robust adaptive immune responses, recent trials have reported encouraging outcomes, with some individuals achieving partial or complete long-term control of HIV-1 after discontinuing ART. These findings raise the possibility that a functional cure for HIV-1 is achievable. In this talk, I will provide an overview of the most promising therapeutic strategies in the pursuit of an HIV-1 cure, including the use of broadly neutralizing antibodies. I will also discuss key populations that may have a higher likelihood of achieving a cure and address the critical barriers that remain in developing effective interventions. Additionally, I will review findings from in-depth studies of the biological mechanisms underlying sustained HIV-1 suppression in individuals who maintain control for years after stopping ART.