PhD defence M.D. (Michael) Röling

The earliest well-described case of an HIV infected individual dates back to 1959(1). The HIV/AIDS pandemic became public in 1981. Since the start of the pandemic 75 million people have been infected and about 32 million people have died(2). In 1987 the first anti-retroviral drug to treat HIV infection, azidothymidine (AZT), was introduced. In the early nineties combinatorial antiretroviral therapy (cART) was developed. Since then HIV infection has become a chronic disease for those who have access to treatment and can afford it. While cART does block viral replication, it does not lead to definitive cure. Once treatment is stopped, viral replication can resume, even after a long time of treatment. In addition to the danger of recurring infection, it is becoming apparent that long-term cART treatment has negative neurological and cardiovascular effects(3). The source of the persistent infection is a latent reservoir of infected cells. This reservoir consists of long-lived memory CD4+ T-cells that contain transcriptionally inactive, but replication competent HIV-1. The need for either a functional cure (in which patients control the infection) or a sterilizing cure (where the virus is eliminated entirely from the body) is clear. “Shock and kill” is a proposed strategy towards a
definitive cure. It proposes the latent virus is “shocked” into active transcription (and virus production) and then “killed” by the immune system or viral cytopathic effects. The first step, of reactivating latent virus requires a specific and complete reactivation of the latent reservoir. Currently no such treatment exists. The focus of this thesis is to gain insight into the molecular mechanisms of latent HIV, to identify druggable targets using unbiased approaches and identify compounds that reactivate HIV-1 gene expression.

The PhD defences do not take place publicly in the usual way in the Senate Hall at campus Woudestein or in the Professor Andries Querido Room at the Erasmus MC. The candidates will defend their dissertation either in a small group or online.