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
HIV Diagnostics Market Key Factor Analysis with Top Players: Abbott Healthcare, Alere Inc, Apogee Flow Systems Ltd
on May 20, 2019 at 5:48 am
May 20, 2019 (Heraldkeeper via COMTEX) -- Global HIV Diagnostics Market is estimated to cross USD 4.9 billion by 2023; as per a new research report by Global Market Insights, Inc. Increasing ... […]
Integrated stepped alcohol treatment reduces alcohol use in people with HIV
on May 20, 2019 at 2:51 am
People with HIV who drink too much were more likely to reduce drinking after undergoing an approach to care known as integrated stepped alcohol treatment, according to a Yale-led study. The finding ... […]
Human Immunodeficiency Virus (HIV) Rapid Test Kits 2019 Global Market Expected to Grow at CAGR 7.23% and Forecast to 2023
on May 20, 2019 at 2:16 am
The analysts forecast the global human immunodeficiency virus (HIV) rapid test kits market to grow at a CAGR of 7.23% during the period 2017-2021. HIV rapid test kits help in determining the presence ... […]
Dental patients told they need HIV tests due to unclean equipment
on May 20, 2019 at 1:50 am
Hundreds of patients at a dental surgery have been told to take HIV tests over fears unclean equipment was used on them. Public Health England (PHE) has been investigating "potential breaches of ... […]
'Stepped' treatment reduces drinking in patients with HIV
on May 19, 2019 at 7:38 am
People with HIV who drink too much were more likely to reduce drinking after undergoing an approach to care known as integrated stepped alcohol treatment, according to a new study. The finding ... […]
For women with HIV, daily life can impede fight against virus
on May 18, 2019 at 5:31 am
Day-to-day struggles prevent many American women with HIV from taking medicines to suppress the AIDS-causing virus, a new study shows. "Survival is a priority over putting a pill in your mouth for a ... […]
Researchers use gene editing to make cells immune to HIV and other infections in Fred Hutch study
on May 17, 2019 at 7:00 pm
HIV infects a human cell. (National Institute of Health Photo) Some viruses, no matter how hard we try, remain resistant to vaccines. Now, researchers are using a different method, gene editing, as a ... […]
Pakistan doctor accused of infecting more than 400 babies and children with HIV
on May 17, 2019 at 9:24 am
A destitute village in Pakistan’s south has been left devastated after more than 500 people – overwhelmingly children – tested positive for HIV in the past two months, in an epidemic attributed to a ... […]
For many HIV+ women, daily survival takes precedence over viral suppression
on May 17, 2019 at 8:01 am
According to scientists who study women infected with HIV, statistics often paint an impressionist view of the lives of these women that misses the granular detail that tells the real story. ... […]
Ocasio-Cortez slams Gilead over HIV drug prices: 'People are dying for no reason'
on May 17, 2019 at 7:33 am
Congress questioned Gilead's CEO about the high price of HIV prevention drug Truvada. Rep. Alexandria Ocasio-Cortez didn't hold back. By Tim Fitzsimons Rep. Alexandria Ocasio-Cortez, D-N.Y., didn't ... […]
via Google News and Bing News