New Ways for Purging the HIV Reservoir

Normally, after antiretroviral therapy (ART) is stopped, the suppressed HIV dwelling inside HIV-positive people reemerge from their dormant state and come alive, quickly replicating new copies of itself and running amok within the body. HIV lies dormant in places in the body called HIV reservoirs, and the virus itself can last for a long time in there. The reservoirs have a half-life of 6 to 44 months according to different studies. These reservoirs are considered by many scientists to be the final hiding place for HIV in the body, and it's become the main goal to find ways to purge these reservoirs and fully eradicate HIV from each HIV-infected patient.

Even with highly active antiretroviral therapy (HAART), it would take more than 70 years to completely decay the HIV reservoirs, making full eradication practically impossible. Therefore, eliminating the reservoirs has to be done without spreading the infection to unharmed cells. The most ideal situation is to somehow purge the HIV reservoirs without activating T-cells, which could leave them susceptible to infection. Histone deacetylase (HDAC) inhibitors have interesting effects, and current studies have hypothesized that HDAC inhibitors may target the dormant HIV reservoirs, possibly getting rid of the virus without the entire body's supply of T-cells activating.

But which HDAC inhibitor can we use in order to achieve this effect? There are three general types of HDAC: Class I, Class II, and Class-111. Studies have suggested that Class I HDAC inhibitors might be the best choice, but other avenues are currently being explored. Trials with valproic acid (VPA), an HDAC inhibitor that is often prescribed to epileptic patients, showed a significant reduction in HIV reservoir size in 3 out of four patients when VPA was added to the HAART regimen. Vorinostat, Givinostat, Belinostat, three prominent HDAC inhibitors, even produced better results in vitro.

A number of different methods are being looked at to deal with the HIV reservoirs, and the majority of the most recent clinical trials are studying the effectiveness of HDAC inhibitors. The goal is to significantly reduce or eliminate the HIV reservoir. Time will tell if researchers ultimately come up with the right combination of drugs and treatment to build a cure, and whether that cure winds up being a functional one or a sterilizing one, it's worth mentioning that important progress has already been made.

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Alain Lafeuillade
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