How can interval dosing with Vorinostat reverse HIV latency?

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A recent study published in the Journal of Clinical Investigation suggested that interval dosing of Vorinostat could allow latent HIV reservoirs to be more easily detected, but that additional measures are likely to be needed for the effective depletion of persistent infection.

In this study, researchers at the University of North Carolina at Chapel Hill (NC, USA) studied 16 HIV-infected, aviremic individuals whose viral loads were controlled with antiviral therapy.

In order to determine the optimal dosing interval, patients were administered Vorinostat at either 48- or 72-hour dose intervals.

When serial Vorinostat exposures were separated by 72 hours, HIV latent reservoirs were detected more easily, suggesting that this may be the optimal dosing regimen for latency reversal by Vorinostat.

Lead author of this study and assistant Professor at the University of North Carolina, Nancie Archin, commented on these finding: “We showed that a single dose of Vorinostat could expose the hidden virus several years ago, but it has taken two studies over the last 5 years to define the proper interval dosing strategy to use Vorinostat safely and effectively. Now we can attempt to chip away the viral reservoir.”

No serious toxicities and few side effects were observed in individuals after a month of treatment with Vorinostat, however no depletion of the latent infection was observed.

Scientists suggest that in order to completely deplete the viral reservoir, this treatment may need to be coupled with an antiviral immune therapy, such as a vaccine or a HIV-specific antibody.

Director of the University of North Carolina’s HIV Cure Center, David Margolis, explained the significance of these findings: “We have now been able to begin two small, intensive studies pairing Vorinostat with an anti-HIV vaccine produced by Argos Therapeutics, or with an infusion of antiviral immune cells prepared by Cath Bollard’s laboratory at Children’s National Medical Center, in an attempt to test combined approaches to clearing HIV infection. We do not expect immediate success, but hope to make progress towards the goal of developing treatments that someday might clear HIV infection.”

Sources: Archin NM, Kirchherr JL, Sung JA et al. Interval dosing with the HDAC inhibitor vorinostat effectively reverses HIV latency. J. Clin. Invest. doi: 10.1172/JCI92684 (2017) (Epub ahead of print); www.eurekalert.org/pub_releases/2017-07/uonc-usa071017.php

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