CHAPEL HILL – A “major step” toward a possible cure for HIV with a technique that targets the virus as it lays dormant in people receiving treatment thus escaping being attacked by current therapy.
So report scientists at UNC-Chapel Hill working with Emory University and Qura Therapeutics which is a partnership between UNC and ViiV Healthcare. ViiV, which is owned by GlaxoSmithKline, focuses on AIDS treatments and maintains a substantial research-and-development operation in RTP.
What UNC calls an “important scientific step toward a cure” involves a “new approach” to deal with HIV latency – i.e. laying dormant in the human body. “[T]his latent reservoir is considered the greatest obstacle to a cure,” UNC noted.
The process can “expose latent HIV,” UNC says, and worked in two different animal model systems “with little or no toxicity.”
The researchers utilized a compound called AZD5582 that activated latently infected CD4+ T cells.
UNC-Chapel Hill HIV researchers David Margolis, MD, and J. Victor Garcia, PhD, along with Rick Dunham from ViiV Healthcare (from left to right). Margolis is director of the UNC HIV Cure Center, which is home to Qura Therapeutics, a company formed through a partnership between UNC-Chapel Hill and ViiV, formerly the HIV research wing of GSK. Photographed January 21, 2020 at the Genetic Medicine Building on the campus of the University of North Carolina at Chapel Hill.
(Jon Gardiner/UNC-Chapel Hill)
“Currently, people with HIV take antiretroviral therapy (ART), which can suppress HIV to undetectable levels in blood, but the virus persists throughout the body in latently infected resting CD4+ T cells,” UNC reports.
CD4+ cells, are a type of T cell that play an important role in the immune system, particularly in the adaptive immune system, according to Wikipedia.
“No cure exists for AIDS, but strict adherence to anti-retroviral therapy (ART) can dramatically slow the disease’s progress, prevent secondary infections and complications, and prolong life,” says the Mayo Clinic.
UNC describes its findings as a “seminal work” toward addressing the needs of 38 million people worldwide (more than 1 million in the US). Many receive antiretroviral therapy (or ART) It “can suppress HIV to undetectable levels in blood, but the virus persists throughout the body.” When the therapy is stopped, so-called “viral loads” of HIV spike, UNC explained. Viral loads is the number of viral particles found in each millilitre of blood, according to the World Health Organization.
From the study
“Long-lasting, latently infected resting CD4+ T cells are the greatest obstacle to obtaining a cure for HIV infection, as these cells can persist despite decades of treatment with antiretroviral therapy (ART),” the researchers wrote in the abstract of their study.
“Estimates indicate that more than 70 years of continuous, fully suppressive ART are needed to eliminate the HIV reservoir1. Alternatively, induction of HIV from its latent state could accelerate the decrease in the reservoir, thus reducing the time to eradication. Previous attempts to reactivate latent HIV in preclinical animal models and in clinical trials have measured HIV induction in the peripheral blood with minimal focus on tissue reservoirs and have had limited effect.”
The HIV findings were published in Nature.
‘Exciting scientific achievement’
“Previously, no one had successfully tested a latency reversal molecule in humans or in an animal model with human cells demonstrating systemic HIV induction in peripheral blood, in resting CD4+ T cells from multiple tissues, and then replicated this success in a completely different species infected with a different virus,” said co-senior author J. Victor Garcia, PhD, director of the International Center for the Advancement of Translational Science, professor of medicine and microbiology & immunology at the UNC School of Medicine.
Added Ann Chahroudi, MD, PhD, associate professor of pediatrics at Emory: “This is an exciting scientific achievement, and we hope this will be an important step toward one day eradicating the virus in people living with HIV.”
The compound was tested on ART-suppressed mouse models with fully functioning human immune cells, the kind typically infected with HIV in humans, UNC said. ART-suppressed rhesus macaques infected with Simian Immunodeficiency Virus (SIV) were tested at Emory.
Qura, UNC and ViiV scientists conducted the basic work that set the stage for the animal model testing. More research is needed, however, before testing can begin on humans, UNC noted.
Such a treatment might find a welcoming audience.
“People with HIV are more likely to consider hypothetical medications that offer a ‘cure’ for the virus than those offering clinical remission,” Aidsmap reported Tuesday, citing research published in AIDS and Behavior.
“These findings could have implications for recruitment to future HIV ‘cure’ studies, with potential participants more likely to join medication trials if a potential outcome is eradication of the virus rather than medicine-free remission.”
