A new strategy deployed against HIV by Western researchers has been able to pull the virus out of hiding in cells and expose it to potential attack from the immune system or open it to further treatment. This strategy may offer a pathway to a cure for those living with the disease.
The study, A targeted reactivation of latent HIV-1 using an activator vector in patient samples from acute infection, was published in the journal eBioMedicine.
Once HIV enters the body, some of the virus hides dormant inside of cells, making it essentially invisible to both the immune system and antiretroviral drugs. This hiding virus is known as the ‘latent reservoir’ and it is what prevents a cure for people living with HIV.
Currently, anti-HIV drugs reduce the virus count in the body to where it cannot be measured by conventional tests and a person lives relatively disease free. However, if they ever stop their lifelong therapy, some of the virus will rapidly re-emerge.
“The aim is to get it all out of dormancy with a targeted punch, so the remaining virus can be killed,” said Eric Arts, a Schulich Medicine & Dentistry professor and principal investigator on the study. “Now that we’ve shown this can be done with patient samples at early HIV disease, the hope is this will lead to targeted cure strategies.”
By studying cells from HIV-positive individuals receiving treatment early in disease, the research team has shown that their formulation – known as Activator Vector (ACT-VEC) – was successful in targeting the latent HIV reservoir. Reactivating this dormant HIV brings it out of hiding so it can be killed by antiretroviral treatment.
“Antiretroviral therapies work by disrupting various aspects of the replication cycle of HIV,” said Jamie Mann, who was involved in the study while at Schulich Medicine & Dentistry and is now a lecturer at Bristol University (U.K.). “If the virus is not replicating, the drugs cannot have an effect on it. By reactivating the virus, we can either inhibit it through antiretroviral therapy or it can be targeted by the body’s immune response.”
Using what is called a ‘shock-and-kill’ strategy, the research team has shown they can pull the virus out of latency – and will now determine if they can activate the body’s immune cells to kill it.
The team looked specifically at the virus hiding inside white blood cells, called T cells. These cells are initiated by the immune response and are some of the most important cells that protect against viral infections, including HIV.
The results from the study show that the virus may actually hide inside of the very cells designed to kill it and help control infection.
“ACT-VEC is designed specifically to activate these cells that had previously responded to HIV that now remain dormant,” Arts said. “This activation has a dual purpose – it stimulates the remaining virus out of dormancy and induces the immune system.”
This ongoing research is uniquely suited to the newly opened state-of-the-art Imaging Pathogens for Knowledge Translation (ImPaKT) facility at Schulich Medicine & Dentistry.
Conducted in collaboration with Case Western Reserve University and Imperial College London, the study was funded by the American Foundation of AIDS Research, The National Institutes of Health, and by the Canadian Institutes of Health Research. A patent has been issued for this potential therapeutic.
