Advances in structure-activity relationships of HDAC inhibitors as HIV latency-reversing agents.

INTRODUCTION: HIV-infected cells may rebound due to the existence of the silent HIV-infected memory CD4+ T cells (HIV latency). This HIV latency makes the disease almost incurable. In latency, the integrated proviral DNA of HIV is transcriptionally silenced partly due to the activity of histone deacetylases (HDACs). Hence, inhibition of HDAC is considered a prime target for HIV latency reversal.

AREAS COVERED: A brief biology and function of HDACs have been discussed to identify key points to design HDAC inhibitors (HDACis). This article summarizes recent achievements in the development of HDACis to achieve HIV latency reversal. Structure-activity relationships (SARs) of some series of compounds were also explored.

EXPERT OPINION: Depletion of the HIV reservoir is the only way to end this deadly epidemic. HDACis are latency-reversing agents (LRA) that can be used to 'shock' the latently infected CD4+ T cells to induce them to produce viral proteins. It is interesting to note that HDAC3, which is extensively expressed in resting T cells, is specifically preferred by benzamide-containing HDACis for inhibition. Thus, the benzamide class of compounds should be explored. Nevertheless, more data on selective HDAC inhibition is needed for further development of HDACis in HIV latency reversal.