NL4Cure: Join forces to accelerate HIV cure

The number of HIV related deaths has greatly decreased since the start of the epidemic in 1981. Nevertheless, 770.000 people died in 2018 as a consequence of HIV. Even though the implementation of combination antiretroviral therapy has been a great contribution to the decrease in the number of HIV related losses it can only suppress the virus to undetectable levels but does not result in eradication of the virus from the body. An effective, safe and at the same time widely accessible cure hasn’t been achieved yet. The viral reservoir is thought to be the main barrier to a cure. HIV hides in the viral reservoirs by integrating into the DNA of host immune cells which makes the virus unreachable for the immune system. A potential strategy towards an HIV cure is the ‘shock and kill’ approach. This approach first ‘shocks’ the cells by latency-reversing agents (LRAs) to induce HIV transcription after which the immune system can ‘kill’ the cells. This research focusses on the ‘shock’ part and more specifically on reversing latency by inducing transcription factors using maraviroc. Treatment with maraviroc results in phosphorylation of NF-ƙB and induction of HIV-RNA transcription in resting CD4+ T cells. This study is part of a bigger collaborative study in which different FDA approved LRAs, kill strategies and combinations thereof will be tested with regards to reversing HIV latency without cytotoxicity. After an estimated study period of two years, the most promising combinations will be translated into a phase I clinical trial. This trial will focus on chronically treated HIV-positive individuals to study the safety and efficacy of a reduction in viral reservoir size.

Contact
Ninée Buchholtz