Tracking and Elimination of hidden HIV-1

Towards a HIV-1 cure: detection and elimination of the HIV-1 reservoir

There is no cure for HIV-1 as the virus hides within immune cells and replication resumes from these so-called reservoirs when antiretroviral therapy is stopped. We have formed a very productive partnership with our industrial partners QvQ, DDL, UniQure and First Health Pharmaceuticals to develop novel methods to detect and eliminate the immune cells wherein HIV-1 hides. We have isolated these cells and by analyzing these cells we have been able to develop a very efficient two-pronged therapy that eliminates these HIV-1 reservoirs. This strategy was efficient in significantly decreasing the HIV-1 reservoir in the blood from people living with HIV-1.

Over 39 million people worldwide are infected with HIV-1 and more than 1 million people become infected yearly. Although antiretroviral therapy suppresses HIV-1 infection, it cannot cure HIV-1. The virus hides within immune cells, the so-called HIV-1 reservoirs. These HIV-1 reservoirs are difficult to detect and so far it has not been possible to specifically eliminate these reservoirs in order to cure HIV-1. There is therefore an urgent need for the development of novel methods to identify and eliminate these HIV-1 reservoirs.

Together with our industrial partners we have developed novel methods to detect and isolate the cells wherein HIV-1 hides. We have isolate and analyzed these HIV-1 reservoirs and were able to identify cellular processes that were specifically activated in these HIV-1 reservoirs. Using this information we have developed a two-pronged therapy that activated the hiding HIV-1 in cells and subsequent induced cell-death of the cells with the reactivated HIV-1. This method allowed us to strongly decrease the HIV-1 reservoir cells in the blood from people living with HIV-1. We will further develop this innovative two-pronged therapy into a cure for HIV-1. Moreover, the methods to identify and isolate the HIV-1 reservoir in people with HIV-1 will allow us to monitor success of different HIV-1 cures and also allow further development of innovative therapies to cure HIV-1.

Thus, together with our industry partners, clinicians and the HIV-1 infected community we have made major steps towards an HIV-1 cure and acquired further financial funding to continue the translation of our research to clinical therapies for an HIV-1 cure worldwide.

Summary

Here we have identified the phenotype of the so-called HIV-1 reservoir of latent infected T cells, and elucidated mechanisms that underlie formation of the HIV-1 reservoir. By targeting these cellular mechanisms we were able to not only reactivate HIV-1 in these HIV-1 reservoirs but also to eliminate the HIV-1 reactivated cells. We have done this in cell-lines but also in blood from people living with HIV-1. Furthermore we have developed various novel strategies to harness the innate immune system to eliminate HIV-1 infected cells and to also target integrated HIV-1 and edit it from the genome. The findings from this project and cooperation with our industrial partners has led not only to insight and novel therapies to cure HIV-1 but also led to new funding opportunities to continue our collaborative research.

Technology Readiness Level (TRL)

3 - 4

Time period

66 months

Partners