Toward a Functional Cure for HIV Infection – HIVFUNCURE

Despite major advancements in HIV-1 treatment that have extended the lifespan of people living with HIV (PLWH), finding a cure remains a significant challenge. Current therapies reduce viremia and improve overall patient health but do not eliminate HIV-1 infection, as proviral DNA persists in cellular reservoirs, causing viral rebound after treatment interruption. Various strategies for HIV-1 cure are under investigation. While Zeger Debyser (KU Leuven) is a pioneer of the “block-and-lock” strategy aimed at the stable silencing of HIV expression (1), Anna Kula-Pacurar (Jagiellonian University, Kraków, Poland) has developed the “shock-and-kill” approach to eliminate HIV-1-infected cells (2). Heng-Chang Chen (Łukasiewicz Research Network – PORT Polish Center for Technology Development) has pioneered virus barcoding technology, which enables correlation of unique integration sites with the transcriptional status of the provirus (3). In this project, the three partners will combine their expertise to explore innovative strategies for a functional cure for HIV.

To achieve this ambitious goal, the project will undertake the following actions:

• Strengthening the LEDGIN-based “block-and-lock” strategy using BRD4 protein modulators
• Investigating “block-and-shock” combinations using LEDGINs and latency-reversing agents
• Examining the selection of latent proviruses in cell culture using both strategies

This collaborative effort will integrate complementary cutting-edge approaches, paving the way toward a functional cure for HIV.