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 infected cells 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 treatment. “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.”
The Latest on: HIV
- Fulton County receives multi-million dollar grant to fight HIVon September 7, 2019 at 9:44 am
ATLANTA — Fulton County is combating HIV with a new, multi-million-dollar federal grant. The $2.5 million federal grant from The Substance Abuse and Mental Health Services Administration will serve ...
- Infant model of HIV opens new avenues for researchon September 6, 2019 at 5:17 pm
Researchers have developed an animal model to test HIV infection and therapies in infants, allowing them to develop biomarkers to predict viral rebound after antiretroviral therapy (ART) interruption.
- Kick HIV Care Out of the Clinicon September 6, 2019 at 1:49 pm
WASHINGTON, DC — More than 50 protesters chanting "You can't end this without us" stormed the stage here at the United States Conference on AIDS 2019 after a presentation on the Ending the HIV ...
- Spate of clinical trials has scientists hopeful about a vaccine to prevent HIVon September 6, 2019 at 8:41 am
First there were the drugs that could knock back HIV to undetectable levels, and the virus was no longer synonymous with a death sentence. Then came a treatment that allowed people who were HIV ...
- Canadian children undergo HIV testing after being pricked with discarded needle at schoolon September 6, 2019 at 6:15 am
A Canadian mother is cautioning other parents after multiple children — including her daughter — were pricked by potentially infected needles at their school. Amy Slater took to Facebook Wednesday ...
- HIV prevention is making progress. And a breakthrough vaccine appears within reachon September 6, 2019 at 6:08 am
First there were the drugs that could knock back HIV to undetectable levels, and the virus was no longer synonymous with a death sentence. Then came a treatment that allowed people who were ...
- Three teams fail to replicate results of 2016 HIV study that claimed 'cure' in monkeyson September 6, 2019 at 6:02 am
Three separate and independent teams of researchers have attempted to replicate the results of a team which, back in 2016, claimed to have cured monkeys of an HIV-like infection. All three have ...
- Pope Francis visits HIV-sufferers on Maputo's outskirtson September 6, 2019 at 5:09 am
Pope Francis on Friday (September 6), his final day in Mozambique, visited a hospital on the outskirts of Maputo which treats HIV-AIDS-infected mothers and their children. Rough cut (no reporter ...
- Spatially clustered loci with multiple enhancers are frequent targets of HIV-1 integrationon September 6, 2019 at 2:16 am
HIV-1 recurrently targets active genes and integrates in the proximity of the nuclear pore compartment in CD4 + T cells. However, the genomic features of these genes and the relevance of their ...
- Pope highlights HIV-AIDS in visit to Mozambique hospitalon September 5, 2019 at 11:28 pm
MAPUTO, Mozambique — Pope Francis is wrapping up his visit to Mozambique by meeting with HIV-infected mothers and children at a Catholic Church-run hospital in one of the countries hardest hit by the ...
via Google News and Bing News