Curing HIV-1 by eliminating its hiding place
Combination antiretroviral therapy (cART) is very potent in suppressing HIV-1 replication and preventing AIDS, but it is not curative. HIV-1 persistence in reservoirs is the major obstacle to an HIV-1 cure, as viral replication rapidly resumes after cART interruption. Within this Target2Cure project, scientists join efforts with key industrial partners to achieve a cure for HIV-1 by developing innovative approaches to identify and eliminate these HIV-1 reservoirs.
Understanding the nature of the HIV-1 reservoir, to identify the phenotype of latent infected cells and develop innovative methods to eradicate the HIV-1 reservoir will not only have a large scientific impact but will also have a tremendous societal impact. Novel non-invasive imaging techniques will be developed as well as monitoring assays for HIV-1 infected individuals undergoing curative strategies. Furthermore, the novel methods for eradication of the HIV-1 infected cells will be paramount to the cure for HIV-1. The participation of the industry partners, and involvement of clinicians and the HIV-1 infected community ensures translation to clinical methods/treatments.
Innovative techniques will be used to identify specific markers expressed by the latent HIV-1 reservoir. The combination studies in patient cohort materials and innovative detection methods has never been explored before. The innovative antibody technology will be used of one of the industry partners to visualize and eliminate the viral reservoir. Recently broadly neutralizing antibodies have been shown to control viral rebound upon treatment interruption. Therefore nanobodies will be developed also in combination with Fc modification to specifically kill the viral reservoir. In addition, compounds activating host factors might provide a novel way to kill latently infected cells. Moreover, gene therapy methods will be explored to excise or inactivate the integrated provirus.
Novel biomarkers will be identified that will be of great value to the clinic for monitoring people living with HIV-1 in clinical studies aiming at cure. The innovative strategies specifically targeting active elimination of the viral reservoir are of great additional value to current cure strategies focusing on latency reversal.