Evaluation of Innovative Combinatorial stratégies of Anti-latency and Anti-immune Activation Drugs Targeting HIV Reservoir

Several barriers prevent the remission of HIV infection: low level viremia, HIV latency in the genome of host infected immune cells and persistent immune activation. Targeting immune activation and viral latency, represent the two intimately intricate goals to be envisaged for purging the reservoir, in the perspective of HIV cure. There is an urgent to develop and to test drugs targeting HIV latency, HIV residual replication and immune activation, alone or in synergistic combinations. We propose in this study to test agents with a potential effect on HIV latency by combining classical agents and newly discovered agents. The Pitié-Salpêtrière virology group has identified some new diaminopiperidine based compounds that have some antilatency properties through an activation of transcription. Compounds of this new class will be tested in combination with classical agents (HDAC inhibitors, HMT inhibitors, inducers of P-TEFb release, PKC agonists, DNMT inhibitors) and less toxic compounds from classical categories for which Carine Van Lint (University of Brussels) has obtained preliminary HIV reactivation data. All the experimentations will be conducted in J-Lat cells and in ex- vivo CD4 cells sampled in patients from the Pitié-Salpêtrière HIV cohort.