Two weeks makes a big difference in treating the animal version of HIV and latent tuberculosis, researchers from the Texas Biomedical Research Institute, the Southwest National Primate Research Center and their colleagues in the Journal d’investigation clinique. The discovery is another puzzle piece of the complex interplay between HIV and tuberculosis (TB), and may help advance the development of therapies and a combination vaccine for the two diseases in humans.
“Most humans are able to control a low dose of TB infection by keeping it in a dormant form called latent TB infection,” says Riti Sharan, PhD, scientist at Texas Biomed and author of the first paper. “But if they are co-infected with HIV, there is a strong possibility that the TB will be reactivated and the patient will eventually die of TB. Our goal is to improve existing interventions or identify new ones to prevent reactivation of latent tuberculosis. »
To help study what happens in humans, researchers are turning to non-human primates, which contract simian immunodeficiency virus (SIV), the simian version of HIV, as well as tuberculosis. Researchers have found that when animals with latent tuberculosis infection start combination antiretroviral therapy (cART) against SIV two weeks after infection, the animals fare significantly better than if cART is started four weeks later. SIV infection.
“We didn’t initially think two weeks would make such a big difference, but to our surprise, it does,” Sharan said. “The results were very dramatic and clear. »
Specifically, in the group that started cART two weeks after infection, chronic immune activation was significantly reduced, as was SIV replication, and latent tuberculosis was not reactivated as much as in the group who started cART four weeks after infection. In fact, the lungs of the group that started treatment at four weeks looked rather untreated.
Chronic or continuous activation of an immune response may seem like a good thing to help fight disease. But it can also play a central role in aggravating the disease. When immune cells are chronically activated, it leads to exhaustion and cell death, which opens up a major gap in the body’s defense system, Sharan explains. It is then that latent tuberculosis appears which can be reactivated.
“This article adds to the growing body of evidence from our lab that shows chronic immune activation is the key to reactivation of latent tuberculosis,” says Deepak Kaushal, PhD, professor at Texas Biomed and lead author of the item. “But it’s the first to really look at the difference in time to deliver ART in animal models, which will be critical for future studies and help develop treatments and vaccines.” »
The researchers note that the two-week difference may not apply directly to humans, in part because most people are unlikely to be diagnosed and start treatment for HIV within two weeks of infection. . The real value of the discovery is to identify chronic immune activation as the primary driver of latent TB reactivation after HIV infection, and now be able to investigate potential mechanisms of protection.
“Ultimately, we aim to use this information to design a therapy that would allow patients to prevent latent reactivation of tuberculosis by limiting chronic HIV-induced immune activation,” Sharan said.
The research was done in collaboration with Emory University School of Medicine, the Tulane National Primate Research Center and Washington University in St. Louis.
This investigation used resources supported by Southwest National Primate Research Center grant P51 OD011133 of the National Institutes of Health Office of Research Infrastructure Programs.
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