THURSDAY, SEPTEMBER 29, 2016

Scripps study shows drug therapy candidate decreases HIV reactivation rate

The Scripps Research Institute's drug candidate decreases the HIV reactivation rate. | Courtesy of sciencedaily.com
Scientists from The Scripps Research Institute’s (TSRI) Florida campus said Wednesday they designed a drug candidate therapy that significantly decreases the HIV reactivation site.

Patients with HIV infections must stay on antiretroviral therapy for their entire lives, as the virus continues living through dormant cells infected with the virus. Interrupting the antiretroviral therapy can cause the virus to rebound and develop into AIDS.

The TSRI researchers said they have demonstrated an alternative to antiretroviral therapies using Cortistatin A, a natural compound that decreases the virus’s residual levels in the dormant, infected cells. The compound creates an almost permanent latency state in the virus and radically reduces the virus’s reactivation capabilities.

“Our results highlight an alternative approach to current anti-HIV strategies,” TSRI Associate Professor Susana Valente said. Valente led the study which was published in the journal mBio. 

“Prior treatment with Cortistatin A significantly inhibits and delays viral rebound in the absence of any drug. Our results suggest current antiretroviral regimens could be supplemented with a Tat inhibitor such as Cortistatin A to achieve a functional HIV-1 cure, reducing levels of the virus and preventing reactivation from latent reservoirs,” Valente said.  

“In our proposed model, didehydro-Cortistatin A inhibits the viral transcriptional activator, Tat, far more completely, delaying or even halting viral replication, reactivation and replenishment of the latent viral reservoir,” Valente said.

The study indicated that didehydro-Cortistatin A inhibits replication in HIV-infected cells by significantly reducing levels of viral messenger RNA 

“In latently infected primary T cells isolated from nine HIV-infected subjects being treated with antiretroviral drugs, didehydro-Cortistatin A reduced viral reactivation by an average of 92.3 percent,” TSRI Postdoctoral Associate Guillaume Mousseau said. Mousseau was the first author of the study and a member of the Valente lab team.

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The Scripps Research Institute 130 Scripps Way Jupiter, FL 33458

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