UH Med Now
HIV and TB: Fighting a Deadly Disease Combination in Children, With New $6.2 M grant to University of Hawaii Manoa and International Partners
Pictured: Lishomwa Ndhlovu, MD, PhD, University of Hawaiʻi, will lead Myanmar clinical study.
Multi-Institutional News Release
About a third of us are walking around with the bacteria that causes tuberculosis (TB) in our bodies, but most don’t actually end up with TB. For children living with HIV – about 2 million at last estimate – it’s a different story. They’re much more likely to develop TB, and about 40,000 HIV-positive children die from it each year.
To explore exactly how HIV puts children at greater risk of contracting and dying from TB, an international team of scientists, led by researchers at the University of Hawaiʻi at Mānoa, University of Pittsburgh, and the University of Wisconsin-Madison and have secured a five-year, $6.2 million grant from the National Institute of Allergy and Infectious Diseases. The grant will fund nonhuman primate experiments to understand disease mechanisms and explore a potential therapeutic approach. Then, extending from the laboratory to the field, Lishomwa Ndhlovu, M.D., Ph.D., professor of tropical medicine in the John A. Burns School of Medicine at the University of Hawaiʻi will investigate whether the same findings are true for children living in Myanmar, where rates of HIV and TB are both high.
“Children with HIV are very vulnerable to TB, and anything we can do to try to better understand the pathology of the disease and potentially develop new interventions would make a great dent in the morbidity and mortality of the two diseases,” Ndhlovu said.
Scanga’s lab is located in Pitt’s Center for Vaccine Research, which is one of the few infectious disease labs in the world equipped with a PET-CT scanner. That imaging technology allows Scanga to observe disease progression in infected animals over time.
Scanga uses adolescent monkeys, age 1.5 to 2 years, which is equivalent to age 10 to 14 in humans. He will infect them with SIV – the monkey version of HIV – and, after several weeks, treat them with antiviral drugs like those used to treat people living with HIV. Next, he will expose them to the bacteria that causes TB.
In Scanga’s previous work with adult monkeys, the SIV-positive animals fared much worse than their SIV-negative counterparts, with faster TB progression.
The reason, Scanga hypothesizes, is that SIV attacks the natural killer T cells and mucosal-associated invariant T cells in the lungs that would normally act as a first defense against TB. In response, these cells produce more of the protein PD-1, which leads to immune exhaustion and failure to respond to invading bacteria.
The next step is to see whether it’s possible to reverse immune exhaustion to fend off TB more effectively. So, Scanga teamed up with Shelby O’Connor, Ph.D., associate professor of pathology and laboratory medicine at the University of Wisconsin-Madison.
They plan to treat SIV-positive monkeys with a cancer immunotherapy drug, a PD-1 blocker, that reverses immune exhaustion so that T cells might better prevent TB bacteria from infiltrating the lungs.
“It’s amazing to me how the interventions for people living with HIV are merging with those used to treat cancer,” O’Connor said. “While the diseases are quite different, there are also many similarities in how an affected person responds to each disease.”
“We are very fortunate to have an ongoing study of HIV in children in Yangoon and we have leveraged that opportunity to see how we can investigate how we can prevent TB in this vulnerable HIV population in children,” said Ndhlovu.
Other collaborators on the grant include Stephen Kent, Ph.D., at the University of Melbourne Peter Doherty Institute for Infection and Immunity in Australia, and Kyaw Linn, M.D., at Mingaladon Specialist Hospital in Yangoon, Myanmar.
Mahalo to Erin Hare of University of Pittsburgh for taking the lead in compiling this multi-institutional release.