Most people can keep a low dose of tuberculosis infection under control by keeping it in a dormant state known as latent tuberculosis infection, according to Texas Biomed researcher Riti Sharan, PhD. Patients who are HIV co-infected face a high risk of reactivation of TB, which would result in their death. Improve or discover new ways to prevent the reactivation of latent tuberculosis (TB).”
SIV, the monkey version of HIV, and tuberculosis are two diseases that nonhuman primates contract to aid in the study of human diseases. If cART is started two weeks after infection, the animals fare better than if it is started four weeks after infection.
In the beginning, we didn’t think that two weeks would make that much of a difference, but Sharan says that it did. “The results were strikingly obvious.”
As a result, chronic immune activation was significantly reduced, as was SIV replication, and latent TB was not reactivated as much in the group that started cART at two weeks post infection compared to the group that started cART four weeks post infection. Those who began treatment at four weeks had lungs that looked as if they had received no treatment at all.
Activating the body’s immune system on a regular basis may sound like a good way to fight illness. However, it can also play a major role in causing or exacerbating a condition. Sharan explains that chronic activation of the immune system leads to exhaustion and cell death, which creates a huge hole in the body’s defense system. Latent tuberculosis may reactivate at this point.
“This paper adds to the growing body of evidence from our lab that shows chronic immune activation is key to driving reactivation of latent TB,” says Deepak Kaushal, PhD, a professor at Texas Biomed and senior paper author. This is the first study to look at the timing difference for administering ART in animal models, which will be crucial for future studies and the development of treatments and vaccines.
This may not be applicable to humans, in part, because most people will not be diagnosed and begin treatment for HIV in the first two weeks after infection. The real significance of this discovery is that it identifies chronic immune activation as the primary driver of latent TB reactivation following HIV infection, allowing researchers to investigate potential protective mechanisms.
As a result, “Ultimately, we aim to use this information to design a therapy that would enable patients to prevent latent TB reactivation by limiting the HIV-driven chronic immune activation,” Sharan says.
Collaborations with Emory University School of Medicine and Tulane National Primate Research Center and Washington University in St. Louis were necessary for the research to be completed.
