Starting antiretroviral therapy early essential to battling not one, but
two killers

Date:
February 15, 2022
Source:
Texas Biomedical Research Institute
Summary:
Medication against the nonhuman primate version of HIV given two
weeks after infection helped keep tuberculosis in check.



FULL STORY ==========================================================================
Two weeks makes a big difference in treating the animal version of HIV
and latent tuberculosis, researchers from Texas Biomedical Research
Institute, Southwest National Primate Research Center and colleagues
report this month in the Journal of Clinical Investigation. The finding
is another piece in the puzzle of the complex interaction between HIV
and tuberculosis (TB), and can help advance development of therapies
and a combined vaccine for the two diseases in humans.


========================================================================== "Most humans are able to control a low dose of TB infection by
maintaining it in a dormant form called latent tuberculosis infection,"
says Riti Sharan, PhD, a staff scientist at Texas Biomed and first paper author. "But if they get co- infected with HIV, then there is a high possibility that TB is reactivated and the patient ultimately dies of
TB. Our objective is to improve existing interventions or identify new
ones to prevent latent TB from being reactivated." To help study what
happens in humans, researchers turn to nonhuman primates, which contract
simian immunodeficiency virus (SIV), the monkey version of HIV, as well
as tuberculosis. The researchers found that when animals with a latent
TB infection start combined antiretroviral therapy (cART) against SIV
two weeks after infection, the animals fare much better than if cART is
started at four weeks post SIV infection.

"Originally, we did not think that two weeks would make this much of a difference, but to our surprise, it did," Sharan says. "The findings were
very dramatic and clear." Specifically, in the group that started cART
at two weeks post infection, chronic immune activation was significantly reduced, as was SIV replication, and latent TB was not reactivated as much
as in the group that started cART four weeks post infection. In fact,
the lungs in the group that started treatment at four weeks looked more
like they were not receiving any treatment at all.

Chronic, or ongoing, activation of an immune response, might sound
like it should be a good thing to help fight illness. But it can also
play a central role in exacerbating illness. When the immune cells are chronically activated, it leads to exhaustion and cell death, and this
opens up a major gap in the body's defense system, Sharan explains. That
is when is appears latent tuberculosis can become reactivated.

"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. "But it is the first to really look at the timing difference for administering ART in animal models, which is will be critical for future studies and helping develop treatments and vaccines." The researchers
note that the difference of two weeks may not directly apply to humans,
in part, because most people are unlikely to be diagnosed and begin
treatment for HIV within two weeks of infection. The real value of the
finding is identifying chronic immune activation as the main driver of
latent TB reactivation following HIV infection, and now being able to
study potential mechanisms for protection.

"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.

The research was done in collaboration with the Emory University School
of Medicine, Tulane National Primate Research Center and Washington
University in St. Louis.

This investigation used resources supported by the Southwest National
Primate Research Center grant P51 OD011133 from the National Institutes
of Health Office of Research Infrastructure Programs.

========================================================================== Story Source: Materials provided by
Texas_Biomedical_Research_Institute. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Riti Sharan, Shashank R. Ganatra, Allison N. Bucsan, Journey
Cole, Dhiraj
K. Singh, Xavier Alvarez, Maya Gough, Cynthia Alvarez, Alyssa
Blakley, Justin Ferdin, Rajesh Thippeshappa, Bindu Singh, Ruby
Escobedo, Vinay Shivanna, Edward J. Dick, Shannan Hall-Ursone,
Shabaana A. Khader, Smriti Mehra, Jyothi Rengarajan, Deepak
Kaushal. Antiretroviral therapy timing impacts latent tuberculosis
infection reactivation in a Mycobacterium tuberculosis/SIV
coinfection model. Journal of Clinical Investigation, 2022; 132
(3) DOI: 10.1172/JCI153090 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220215152857.htm

--- up 10 weeks, 3 days, 7 hours, 13 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)