New research opens the door to 'functional cure' for HIV

October 17, 2017, The Scripps Research Institute
The authors of the new study included (left to right): Susana Valente, Cari F. Kessing and Chuan Li. Credit: The Scripps Research Institute

In findings that open the door to a completely different approach to curing HIV infections, scientists from the Florida campus of The Scripps Research Institute (TSRI) have for the first time shown that a novel compound effectively suppresses production of the virus in chronically infected cells, and prevents viral rebound, even when those infected cells are subjected to vigorous stimulation.

The study, led by TSRI Associate Professor Susana Valente, was published online Oct. 17 before print in the journal Cell Reports.

"No other anti-retroviral used in the clinic today is able to completely suppress viral production in in vivo," Valente said. "When combining this drug with the standard cocktail of anti-retrovirals used to suppress infection in humanized mouse models of HIV-1 infection, our study found a drastic reduction in virus RNA present—it is really the proof-of-concept for a 'functional cure.'"

Valente, a pioneer in this new approach, calls it "Block-and-Lock"—the approach blocks reactivation of the virus in cells, even during treatment interruptions, and locks HIV into durable state of latency.

Valente and her colleagues use a derivative of a natural compound called didehydro-Cortistatin A (dCA), which blocks replication in HIV-infected cells by inhibiting the viral transcriptional activator, called Tat, halting viral production, reactivation and replenishment of the latent viral reservoir.

"Combining dCA with anti-retroviral therapy accelerates HIV-1 suppression and prevents viral rebound after treatment interruption, even during strong cellular activation," Valente said. "It's important to note that our study uses the maximum tolerable dose of the drug—with virtually no side effects."

The scientists studied the combination therapy in a mouse model of HIV latency and persistence. Once the combined treatment regimen was halted, viral rebound was delayed up to 19 days, compared with just seven days in mouse models receiving only anti-retroviral treatment.

"This demonstrates the potential of 'block-and-lock' strategies," said TSRI Research Associate Cari F. Kessing, co-first author of the study. "This study shows that a 'functional cure' approach can succeed in reducing residual virus in the blood during anti-retroviral treatment and limiting viral rebound during treatment interruption."

"In half of the dCA treated mice, the virus was undetectable for 16 days after all treatment was halted," said the University of North Carolina's Christopher Nixon, another first author.

"We blocked Tat, and the cell's machinery did the rest," said TSRI Research Associate Chuan Li, a coauthor of the study. "The result was that the HIV promoter becomes repressed."

Valente pointed out that the animal models were exposed to just a single month of . "That's a relatively short period of time," she said. "We think longer treatments will result in longer, or even permanent, rebound delays. The question is how long? We're studying that now."

Because any viral rebound of HIV comes with a host of adverse effects, Valente noted, blocking that rebound would automatically reduce those effects.

"This is the only class of drugs that stops infected cells from making viruses outright," said Valente. "All current antivirals work later in the viral lifecycle, so only a HIV transcriptional inhibitor like dCA can stop the side effects of low-level virus production."

In addition to Valente, Kessing, Li and Nixon, other authors of the study, "In Vivo Suppression Of HIV Rebound By Didehydro-1 Cortistatin A, A 'Block-And-Lock'  Strategy For HIV-1 Treatment," are Guillaume Mousseau and Mohammad Fallahi of TSRI; Perry M. Tsai, Phong T. Ho, Jenna B. Honeycutt and J. Victor Garcia of the University of North Carolina; and Hiroshi Takata and Lydie Trautmann of Walter Reed Army Institute of Research and the Henry M. Jackson Foundation for the Advancement of Military Medicine.

Explore further: Designed drug candidate significantly reduces HIV reactivation rate

More information: Cari F. Kessing et al, In Vivo Suppression of HIV Rebound by Didehydro-Cortistatin A, a "Block-and-Lock" Strategy for HIV-1 Treatment, Cell Reports (2017). DOI: 10.1016/j.celrep.2017.09.080

Related Stories

Designed drug candidate significantly reduces HIV reactivation rate

July 8, 2015
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 ...

Scientists show potent new compound virtually eliminates HIV in cell culture

July 19, 2012
A new study by scientists on the Florida campus of The Scripps Research Institute shows, in cell culture, a natural compound can virtually eliminate human immunodeficiency virus (HIV) in infected cells. The compound defines ...

A new method for removing cells infected with the AIDS virus

October 2, 2017
With the successful suppression of the AIDS virus (HIV) through medication, the focus turns toward its eradication. Researchers from Kumamoto University in Japan have developed a new compound that is key to the destruction ...

Reengineered immune system cells show early promise against HIV

October 12, 2017
Improving on a previous attempt, scientists have developed a new strategy that could potentially be used to reengineer a patient's own immune system cells to fight HIV. The approach, described in PLOS Pathogens, shows benefit ...

VRC01 antibody prolonged time to HIV viral rebound after treatment interruption

July 25, 2017
A new study has shown that infusion of a broadly neutralizing antibody (bNAb) in virally suppressed, early treated volunteers was associated with a modestly delayed rebound of HIV after interruption of antiretroviral therapy ...

Researchers identify a new HIV reservoir

April 17, 2017
HIV cure research to date has focused on clearing the virus from T cells, a type of white blood cell that is an essential part of the immune system. Yet investigators in the Division of Infectious Diseases at the University ...

Recommended for you

Proof-of-concept HIV immunotherapy study passes Phase 1 safety trial

September 21, 2018
Preliminary results from a phase I clinical trial have demonstrated the safety and tolerability of a cell therapy involving the ex vivo expansion of T cells and their subsequent infusion into HIV-infected individuals previously ...

FRESH program combines basic science with social benefits for women at risk of HIV

September 14, 2018
A program established by investigators from the Ragon Institute of Massachusetts General Hospital (MGH), MIT and Harvard is addressing the persistently elevated risk of HIV infection among young women in South Africa from ...

New study finds HIV outbreak in Indiana could have been prevented

September 13, 2018
An HIV outbreak among people who inject drugs in Indiana from 2011 to 2015 could have been avoided if the state's top health and elected officials had acted sooner on warnings, a new study by the Yale School of Public Health ...

Largest study of 'post-treatment controllers' reveals clues about HIV remission

September 13, 2018
Most HIV patients need to take daily anti-retroviral therapy—if they suspend treatment, HIV will rebound within 3-4 weeks. But clinical trials have revealed that a small fraction of patients can stop taking medications ...

Very few sexually active gay and bisexual men use prophylactic drug to prevent HIV transmission, study finds

September 12, 2018
Only 4 percent of sexually active gay and bisexual men in the United States use Truvada, a highly effective medication used to prevent the transmission of HIV, according to the results of a first-of-its-kind study.

Special antibodies could lead to HIV vaccine

September 10, 2018
Around one percent of people infected with HIV produce antibodies that block most strains of the virus. These broadly acting antibodies provide the key to developing an effective vaccine against HIV. Researchers from the ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.