![]() ![]() Using drugs to block the elements needed for the virus to reactivate could shift HIV from a transient latent state to a robustly silenced one. “With the ‘block and lock’ approach, we basically want to push HIV into becoming like a harmless, ancient virus.” “We have shown that blocking Tat with certain drug-like small molecules can lock HIV in its dormant stage, and this block stays in place for some time, even if antiretroviral therapy is interrupted,” says Susana Valente, PhD, one of the principal investigators of the HOPE Collaboratory and associate professor of immunology and microbiology at Scripps Research in Florida. The scientists are testing drugs that would permanently silence HIV without the need for daily antiretroviral therapy. Two particular elements-a sequence of DNA at the start of HIV’s genetic code and a protein called Tat-are needed for latent HIV to reactivate and begin replicating. Researchers have found that these ancient inactive viruses are missing several genetic elements that HIV contains. However, unlike HIV, the ancient viruses remain in a silenced state or are defective. HIV also integrates into the genome of a person living with HIV. The inspiration for the “block and lock” part of their strategy comes from ancient viruses that have integrated themselves into the human genome over millions of years of evolution. The researchers involved in the HOPE Collaboratory are calling their new, alternative tactic “block-lock-excise,” and it targets latent HIV in new ways, without reactivating it. And even a small remaining reservoir of latent virus means that someone living with HIV must remain on daily treatments. Most attempts at curing HIV have centered around purposefully reactivating the latent virus in order to flush it out in the presence of antiretroviral therapy-an approach called “shock and kill.” But researchers have struggled to reactivate every copy of the virus in the body, or at least, to do so without severe undesirable side effects. Moreover, a lapse in this daily therapy can lead to a rapid rebound of the infection. HIV is notorious for its ability to hide in a latent state in immune cells while latent viruses don’t cause overt symptoms or full-blown AIDS, they can lead to long-term health complications for those living with HIV and can’t be targeted with standard antiretroviral therapy. At Gladstone, the team includes (from left to right) Nadia Roan, Danielle Lyons, Warner Greene, and Melanie Ott. The HOPE Collaboratory is searching for a cure for HIV. The HOPE Collaboratory is one of 10 groups awarded a 5-year grant under the Martin Delaney Collaboratories program, the flagship program on HIV cure research at the NIH. “I think it’s extremely important for us to explore a broad range of scientific approaches to find the best cure for people living with HIV, as quickly as we can.” “This is a fundamentally different approach to targeting HIV than what everyone else has been trying,” says Melanie Ott, MD, PhD, director of the Gladstone Institute of Virology, and the program director and a principal investigator of the HOPE Collaboratory. Their approach, which aims to both silence and permanently remove HIV from the body, takes advantage of knowledge about how other viruses have become naturally inactivated over time. The group, known as the HIV Obstruction by Programmed Epigenetics (HOPE) Collaboratory, will be led by researchers at Gladstone Institutes, Scripps Research Florida, and Weill Cornell Medicine. ![]() Now, with a $26.5-million grant from the National Institutes of Health (NIH), a multi-disciplinary group of researchers from institutions around the world is trying a completely new strategy for curing HIV. But attempts to completely eliminate the virus from the bodies of people living with HIV, curing them for good, have failed. ![]() Over the last 40 years, HIV has shifted from a deadly and mysterious virus to one that can be controlled with daily drugs. ![]()
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