Unlike other antiretroviral therapies, a natural compound reduces residual levels of HIV from infected dormant cells, greatly diminishing the virus' capacity for reactivation, scientists have found.
HIV-infected patients remain on antiretroviral therapy for life because the virus survives over the long-term in infected dormant cells.
Interruption of current types of antiretroviral therapy results in a rebound of the virus and clinical progression to AIDS.
Now, scientists from the Florida campus of The Scripps Research Institute (TSRI) have shown that a natural compound called Cortistatin A reduces residual levels of virus from these infected dormant cells, establishing a near-permanent state of latency and greatly diminishing the virus' capacity for reactivation.
"Our results highlight an alternative approach to current anti-HIV strategies," said Susana Valente, a TSRI associate professor who led the study.
"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," she said.
Cortistatin A, which was isolated from a marine sponge, Corticium simplex, in 2006, and in 2008, was first synthesised by TSRI chemist Phil Baran.
A configuration of the compound, didehydro-Cortistatin A, was shown in earlier studies to target the protein Tat, which exponentially increases viral production.
The new study shows that didehydro-Cortistatin A inhibits replication in HIV-infected cells by significantly reducing levels of viral messenger RNA - the blueprints for producing proteins and more infection.
"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 per cent," said Guillaume Mousseau, the first author of the study and a member of the Valente lab.
The study was published in the journal mBio.
