Histone deacetylase inhibitors used in the reversal of latent HIV do not compromise immune function
April 23, 2019
New research shows that histone deacetylase inhibitors (HDACi), which may be used to reverse latent HIV in resting CD4 T cells, do not negatively impact the function of natural killer (NK) cells or impair immunity of HIV-positive patients undergoing antiretroviral therapy (ART).
David Margolis, MD, professor in the Department of Epidemiology at the UNC Gillings School of Global Public Health and director of UNC’s HIV Cure Center, is co-author of the paper “In-vivo administration of histone deacetylase inhibitors does not impair natural killer cell function in HIV+ individuals,” which was published online March 15 in AIDS.
Margolis also is a professor in the UNC School of Medicine’s Department of Microbiology and Immunology. Other authors from the HIV Cure Center include lead author Carolina Garrido, PhD, instructor, and co-authors Brigitte Allard, MS, research specialist, Natalia Soriano-Sarabia, PhD, instructor, and Nancie M. Archin, PhD, assistant professor, all with the School of Medicine.
ART cannot target HIV in cells where the virus has become latent or dormant, which has made it difficult to find a cure for HIV. In order to eradicate HIV, latent virus must be reactivated to induce HIV-RNA and antigen expression for clearance from the body. However, a compromised immune system cannot effectively clear those antigens, making the development of a latency reversal agent without a negative impact on NK cells and the immune system vital to a true cure for HIV.
For this clinical trial, blood cells from HIV-positive participants receiving treatment with either Vorinostat or Panobinostat — both drug compounds that inhibit histone deacetylases — were evaluated to test the treatments’ impacts on the cells. The team found no impairment of NK cell function during treatment with either drug, and the Vorinostat appeared to increase expression of certain NK cells.
Margolis says the goal is to develop latency reversing treatments that will make the virus vulnerable and pair those with immunologic/clearance therapies to clear the formerly hidden, latent infections from the body. These findings show promise that HDACis, when introduced to trigger latency reversal, do so without putting a patient’s immune system in danger.
“HDAC inhibitors allows the disinhibition of some genes, and the hope is that the disinhibition of latent HIV will lead to its expression and vulnerability to clearance, though this has yet to be proven,” Margolis said. “The hope is also that the effect on other cellular genes will be modest and tolerable. Our research shows that the use of HDAC inhibitors in HIV-positive people has been safe.”
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