Lewin's clinical research efforts have focussed on potential HIV cure strategies, particularly those using the epigenetic modifiers including histone deacetylase inhibitors (HDACis). In vitro experiments showed that HDACis such as entinostat, metacept-1 and -3 could activate latent HIV in primary T cells. Following a sabbatical working with Christine Katlama and Brigitte Autran at the Hopital Pitié-Salpêtrière and Université Pierre et Marie Curie (UPMC), Paris, Lewin began to focus more on moving potential cure strategies into clinical trials. Lewin's lab conducted the first multi-dose proof-of-concept HDACi trial in HIV positive participants, administering vorinostat daily over a 14-day period and assessing safety and impact on HIV transcription and reservoirs. The trial and follow-on study showed that while vorinostat was safe and able to increase HIV transcription in most participants, it did not reduce the HIV reservoir. A dose-escalation study conducted in Melbourne, Australia and San Francisco, California, USA of the anti-alcohol compound Disulfiram also showed the ability to increase levels of cell-associated unspliced HIV RNA. Both vorinostat and Disulfiram are now being investigated as part of a combination approach to latency activation ('kick' or 'tickle') followed by a second intervention to remove cells harbouring reactivated virus ('kill' or 'tease').
