Oct 202017
 

Authors of the new study included (left to right): Susana Valente, Cari F. Kessing and Chuan Li.

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.”

Learn more: New Research Opens the Door to ‘Functional Cure’ for HIV

 

The Latest on: HIV
  • Israel AIDS Task Force demands asylum seekers with HIV not be deported
    on February 21, 2018 at 5:01 pm

    The Israel AIDS Task Force is imploring the government to allow Eritrean and Sudanese migrants with HIV to remain in treatment in Israel amid the pending April 1 mass expulsion of 20,000 unmarried African men of working age. Out of a total population of ... […]

  • New HIV cases up 3,147% in the Philippines as crisis gets worse
    on February 21, 2018 at 4:38 pm

    HIV in the Philippines has been described as a national emergency, with the latest figures confirming the worst. New HIV cases in 2017 hit 11,103, which was an almost 20% jump on 2016’s figure of 9,264 cases. That means in the past 10 years, HIV ... […]

  • Advocates: Transmission laws hinder HIV/AIDS prevention efforts
    on February 21, 2018 at 12:17 pm

    Laws that penalize intimate partner contact wherein one person has failed to inform the other that they are HIV-positive are viewed by many advocates and service providers as retrograde, unnecessary and even harmful, according to members of a panel that ... […]

  • HIV Guideline Update
    on February 21, 2018 at 9:46 am

    Peter L. Salgo, MD; Michael Sension, MD; Jeffrey Dunn, PharmD; and Elly Fatehi, PharmD, MPH, review the updates to the HHS treatment guideline for most people with human immunodeficiency virus. Peter L. Salgo, MD: Let’s take a look at the DHHS guidelines ... […]

  • New Study Reveals How A Specific Colonial Legacy Determines Female HIV Rates in Africa
    on February 21, 2018 at 9:36 am

    80% of all HIV positive women in the world live in sub-saharan Africa. This is the only region in the world where more women than men are living with HIV — scholars have referred to this phenomenon as the “feminization of HIV.” The paper, by Siwan ... […]

  • Mylan's HIV combo pill gets FDA tentative nod
    on February 21, 2018 at 8:32 am

    Acorda Therapeutics' new-drug application for inhaled Inbrija, or levodopa, which is being developed to treat off periods in patients with Parkinson's disease who are currently on a carbidopa/levodopa regimen, was accepted by the FDA for review. The agency ... […]

  • Mann Award winner searches for HIV's Achilles' heel
    on February 21, 2018 at 7:05 am

    Yi Wen, center, with advisers Gerald Feigenson, left, and Volker Vogt in a lab in the Biotechnology Building. Viruses are the most abundant biological entities on Earth, capable of infecting every type of life form: animals, plants and bacteria. The ... […]

  • How HIV Evades the Immune System
    on February 21, 2018 at 2:55 am

    HIV is a lentivirus, a type of retrovirus, or RNA-based virus. When the virus enters cells, its single-stranded RNA genome is reverse-transcribed into double stranded DNA by reverse transcriptase. Viral DNA is then imported into the nucleus and integrated ... […]

  • The Philippines Is Seeing a Huge Increase in HIV Cases
    on February 20, 2018 at 1:21 pm

    The stigma and lack of information surrounding resources, testing, and sexual health in general makes people vulnerable to HIV. And while it’s confirmed that cases of HIV have been decreasing globally as of 2016, individual countries’ epidemics have ... […]

  • Philippines: HIV cases up 3,147 percent in 10 years
    on February 19, 2018 at 10:37 am

    New HIV cases continued to increase in the Philippines in 2017 with a 3,147 percent surge since 2007, according to an Al Jazeera analysis of the latest data published by the country's health agency, bucking a downward trend worldwide. In a February 2018 ... […]

via Google News and Bing News

Other Interesting Posts

Leave a Reply

%d bloggers like this: