Histone deacetylase plays an important role in HIV latency. Novel histone deacetylase inhibitors, CG05 and CG06, were evaluated for their roles in HIV latency using ACH2 cells. Both inhibitors were highly efficient in reactivation of provirus and exerted lesser toxicity compared with other known histone deacetylase inhibitors. Histone acetylation increased when proviruses were reactivated by the compounds. These new inhibitors may contribute to the reduction of the HIV reservoir when used in conjunction with highly active antiretroviral therapy.