Inducible cell death (ICD): an innovative approach towards latency reversal and HIV cure in chronic HIV infected patients. (ICD-CHRONO study)

Finding a cure for HIV is essential to make this devastating disease history. Erasmus MC University Medical Center together with Gilead Sciences combine forces in the CHRONO project to discover new ways to cure HIV that will help ending the HIV epidemic.

The United Nations estimates that the HIV pandemic approaches over 40 million people and set the ambitious goal to end HIV/AIDS by 2030. Stigma still exists and without a cure, all people with HIV need therapy which puts huge logistical and financial burdens on often already vulnerable societies, apart from that this strategy is also associated with an ongoing risk of side-effects and viral resistance. Despite all preventive measures and one of the best care infrastructures in the world, the number of people living with HIV is also still increasing in the Netherlands. New ways to end HIV, in the Netherlands and worldwide, are urgently required.

The major obstacle to cure HIV is a persistent reservoir of virus in latent (sleeping) infected immune cells called memory CD4+T-cells. Here, HIV hides silently in our own genome when someone is on antiretroviral drugs, but will cause disease progression to AIDS once therapy is stopped. In the CHRONO project, we will selectively target the HIV reservoir of patients with HIV, by exploiting existing cellular pathways to induce reservoir cell death through innovative drug combinations that we identified. This is called shock&kill.

This study will be done with the help of people living with HIV and under care at Erasmus MC who will undergo leucapheresis. With the identification of a successful strategy to eradicate the reservoir, we can potentially resolve the HIV pandemic.

We have established a unique longitudinal cohort of People living with HIV-1 who started antiviral treatment during the chronic phase of infection, and we have characterized the decay dynamics of the reservoir longitudinally at the level of different molecular compartments using different state of the art technologies. In WP2, we have developed a specific and sensitive inducible reservoir quantitation technique, SQuHIVLa which we have successfully implemented and validated in studies conducted with actual patients, demonstrating the effectiveness and reliability of the technology in practical scenarios. As a result, the research has transitioned from the laboratory to real-world application, indicating a significant advancement towards practical implementation and eventual commercialization of the technology.