Advancements in HIV-1 cure strategies Combining agents to reverse viral latency and shape antiviral immunity

Achieving an HIV-1 cure remains a major scientific challenge, as the virus persists in long-lived latent reservoirs despite effective antiretroviral therapy. This thesis explores strategies aimed at achieving durable remission by combining approaches that both reduce the viral reservoir and strengthen immune responses.
A central focus is the use of host-directed therapies to reverse viral latency and promote the selective elimination of infected cells. By targeting cellular pathways involved in viral persistence and cell survival, these strategies aim not only to “shock” the virus out of latency but also to make infected cells more susceptible to cell death. The findings show that combining different host-targeting compounds enhances viral reactivation and facilitates clearance of infected cells without harming uninfected bystander cells.
In addition, the thesis investigates ways to stimulate innate immune pathways to boost antiviral immunity. Immune agonists and vaccine adjuvants were shown to activate key immune cells and, in some cases, reduce the size of the inducible viral reservoir. These results highlight the potential synergy between latency reversal and immune stimulation.
Overall, this work supports the concept that an effective HIV-1 cure will likely require combination strategies that integrate reservoir reduction with enhanced immune control.