HIV virus stayed dormant for more than 2 weeks after Tat inhibitor dCA ‘blocked-and-locked’ HIV-infected cells.
A newly-developed HIV therapy has been shown to halt the virus’s replication, and could provide a ‘functional cure’ to HIV, according to scientists at Scripps Research Institute.
Researchers used a new approach called ‘block-and-lock,’ for the creation of the new drug compound: didehydro-Cortistatin A (dCA). When used in combination with antiretroviral therapy (ART), dCA may reduce an infected person’s viral load to levels where HIV can no longer spread to healthy cells.
This new discovery comes a month after the Centers for Disease Control and Prevention (CDC) announced that when viral load is undetectable, it’s effectively untransmittable.
Scientists studied the combination therapy in a mouse model of HIV latency and persistence. Mice were infected with human HIV cell, and then given ART and dCA every day for 1 month.
Once the combined treatment regimen was halted, viral rebound was delayed up to 19 days, compared to 7 days in mouse models receiving only ART. The virus stayed below the detectable level more than twice as long as it did with standard treatment, indicating that dCA may have lasting effects.
The animal models were exposed to just a single month treatment, but scientists question if longer treatments will result in longer, or even permanent rebound delays.
The dCA therapy targets the Tat protein, a powerful activator for the process of copying the virus. Once the viral load is reduced to undetectable levels by ART, dCA ‘blocks’ infected cells from reactivating and copying themselves, and then ‘locks’ the HIV virus into a dormant state, which could suppress it for as long as 19 days, according to the study’s results.
Tat is responsible for some of the neurological symptoms of HIV, so dCA could help restore, or at least prevent, the progression of problems with motor skills and memory for those with HIV.
Lead study author, Susana Valente, PhD, The Scripps Research Institute, said the therapy has the potential to suppress the virus for longer periods of time, so 1 missed pill may not cause too much disruption of treatment. Over time dCA may have an impact on the size of HIV-infected cells, to a point that the immune system could suppress the virus on its own. While dCA is in the early stages, it has promising, durable effects on viral load.
Alone, ART keeps the virus repressed, but there’s still a bit of HIV RNA, which allows HIV to continue to be copied. dCA eliminates the risk posed by the small amount of remaining virus.
While dCA doesn’t eliminate the need for ART, the 'block-and-lock' approach is a viable alternative for a functional cure. It's the first time pharmacological inhibition of viral rebound after a break in treatment has been shown in an in vivo model of HIV infection. Study results strongly support the rationale for the inclusion of specific HIV transcriptional inhibitors in eradication strategies.
The study, “In Vivo Suppression of HIV Rebound by Didehydro-Cortistatin A, a “Block-and-Lock” Strategy for HIV-1 Treatment,” was published in Cell Reports.