Trying to Eradicate the Reservoir

The HIV reservoir in latently HIV infected cells is considered one of the major remaining obstacles for eradication of HIV. Researchers hope to treat HIV infected patients who are receiving antiretroviral therapy (ART) with drugs that induce HIV expression in latently infected cells so that they can then try to remove or kill those cells. 

Recently, David Margolis from the University of North Carolina at Chapel Hill reported promising results from one of the first Phase I human trials with one such drug, a histone deacetylase (HDAC) inhibitor called SAHA or vorinostat. In a handful of patients, he reported that the drug leads to an increase of HIV RNA expression (see In Pursuit of a Cure, IAVI Report, Jan.-Feb. 2012). 

But here at the meeting, Jana Blazkova and Tae-Wook Chun from the National Institute of Allergy and Infectious Diseases reported that a 48-hour SAHA treatment of resting CD4+ T cells taken from HIV-infected individuals on ART did not increase HIV RNA expression compared with untreated CD4+ T cells. 

Margolis said one possible reason for the difference between these and his observations could be that 48 hours might be too long as a treatment. “Exposure to these drugs at this concentration can probably have nonspecific effects on the cell,” he said, adding that 48 hours is much longer than it takes for one dose of the drug to be cleared out of the body. 

Eric Verdin from the University of California in San Francisco and one of the discoverers of SAHA, was also not convinced that these results are the last word on the issue. He said there could be many possible reasons for why SAHA failed to have an effect. “In my mind, positive results have 100 times more value than negative results,” he said.