The role of monoclonal antibodies and latency-reversing agents in HIV-1 curative strategies

2021.02.24 | Graduate School of Health

On Friday 19 March at 14:00, Jesper Damsgaard Gunst defends his PhD dissertation entitled "The role of monoclonal antibodies and latency-reversing agents in HIV-1 curative strategies".

Antitretroviral therapy (ART) has transformed HIV-1 infection from a fatal disease into a chronic condition, but ART is not curative. HIV-1 mostly infects and replicates in activated CD4+ T cells, but a proportion of these infected CD4+ T cells will transit into resting memory state with replication-competent provirus integrated. These latently infected resting CD4+ T cells represent the HIV-1 reservoir. HIV-1 infection can be controlled by ART, but in most virally suppressed HIV-1-infected individuals, viral rebound occurs 4 weeks following ART interruption.

In the “shock and kill” approach a latency-reversing agent (LRA) is used to (re)active viral transcription in the latently infected cells, exposing these cells to killing by either viral cytopathic effects or immune-mediated clearance while on ART in order to prevent infection of new cells. Preclinical studies have shown that HIV-1-specific cellular immunity needs to be augmented prior to efficient killing of latently infected cells (re)activated with LRA. One approach to enhance immune-medicated clearance of the latency infected cells is by broadly neutralizing anti-HIV antibodies (bNAbs) followed by latency reversal with histone deacetylases inhibitors (HDACi). In two clincal trials this approach was tested using the bNAb 3BNC117 and HDACi romidepsin    

The summary is written by the PhD student.    

The defence is public and takes place online. Please read the attached press release for more information.

Contact:

PhD student Jesper Damsgaard Gunst

Mail: jesper@gunst.dk 

Phone: (+45) 2388 6636

Read full press release