Restoring and improving gut health may be key to slowing HIV progression to AIDS, according to a study conducted in monkeys.
The research, published in the journal JCI Insight, shows that tackling only systemic immune activation — a strong predictor of progression of human immunodeficiency virus type 1 (HIV-1) disease — and inflammation when attempting to control disease progression and comorbidities is not effective.
The study performed with simian immunodeficiency virus (SIV), the monkey form of HIV, found that treatments should target the root cause of those problems and focus on healing the gut.
“Every study so far targeting systemic inflammation by addressing immune activation has had very short-lived results,” said study lead author Cristian Apetrei, professor at the University of Pittsburgh in the US.
“Upon reflection, we realised those results told us something very important: Inflammation generated by the virus damaging the intestinal lining is driven by a separate mechanism from immune activation. We just had to prove it,” Apetrei said.
The hallmark of HIV infection is the hijacking of immune cells called ”helper T cells” to make copies of the virus.
Scientists have focused on treatments that stop this replication process.
However, virus suppression only “calmed” immune activation and inflammation but did not restore them to pre-infection levels.
For decades, scientists have also known that the gut is an immediate target of HIV. Within weeks of infection, the virus depletes the vast majority of immune cells in the intestines that are the depository of immunologic memory and protect the gut against invading pathogens.
When these cells are destroyed, the intestinal lining gets damaged, and gut flora enters the bloodstream.
However, past thinking was that calming immune activation and stopping HIV replication was key to controlling disease progression and that gut health was a sideshow.
The researchers found that when African green monkeys get SIV, the virus does not cause the type of gut damage seen in humans and some other nonhuman primates, and they don’t naturally progress to chronic infection and AIDS.
The team artificially induced persistently high levels of immune activation in the monkeys, but after more than 100 days, they still had not progressed to chronic infection, something that would be expected in less than half that time in other species. ”In this study, we have directly demonstrated that intestinal dysfunction is the main determinant of systemic inflammation and disease progression,” said study senior author Ivona Pandrea, professor at Pitt Public Health.
“This points to an urgent need for therapies aimed at preserving gut integrity to avoid accelerated ageing, comorbidities and premature death in people living with HIV,” Pandrea said.
The team suggests that the findings should also prompt studies testing whether attempting to heal the guts of people living with HIV through diet, pre- and pro-biotic supplements, and gut microbial transplants slows the progression of the virus. Some of these strategies are being tested in their labs.
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