Not All HIV Reservoirs Are Alike, But Is That A Good Thing?

The scientific community continues to push the limits of what we know about HIV treatment. Each new discovery gives scientists a better understanding of how HIV should be targeted, and recently they found a big piece of the puzzle.

HIV reservoirs are one of the main barriers to a cure. The virus can remain dormant in these reservoirs for years, even while a person is on treatment and undetectable. Once someone stops treatment, these cells awaken and start multiplying all over again, allowing viral loads to rebound. Reservoirs have been found throughout the body — including in the brain, lymph nodes, blood, and digestive tract.

The most common HIV reservoirs have been found in infected immune system T cells. Scientists have often framed their studies around the idea that microphages, a type of white blood cell in our immune system abundant in the body, can also hold HIV reservoirs and act the same way. But a new study from Johns Hopkins Medicine suggests that’s simply not true.

Researchers examined microphages found in the liver and showed that, though HIV can remain in liver immune cells after someone is on treatment, it only does so for a period of time. The scientists found that HIV in liver microphages pretty much die off after a person is on antiretroviral treatment for about a year.

Dr. Ashwin Balagopal, the study’s lead author, says his team examined liver microphages because they comprise 80 to 90 percent of all microphages in the body. While microphages are abundant in our bodies, they are difficult to locate because they are buried deep in tissue or organs.

Johns Hopkins has been transplanting livers for more than 50 years, and the research team has been able to study livers that would have otherwise been discarded. (Until recently, all organs from HIV-positive people legally had to be discarded rather than transplanted into another person; now other people living with HIV can receive them.)

“There has been a number of transplants involving HIV-positive people who have been suppressed for a very long time,” Balagopal says, adding that his team examined liver microphages hoping to find reservoirs, to show that strategies targeting reservoirs in T cells “may be missing an important part of the story.”

Instead, the findings, which were published in the October 2018 issue of Journal of Clinical Investigation, showed that the HIV in liver microphages shouldn’t even be classified as an HIV reservoir, given that the virus inside is unable to replicate itself like the virus found inside T cells.

“I think it tells us, in terms of a cure, that we don’t need to worry about a large population of cells that scientists have been worrying about for some time,” Balagopal says, adding, “It’s fair to say that the treatments people currently take probably address the liver microphages just fine.”

The discovery will allow researchers to better target efforts for a potential cure (because any cure must find, “wake,” and kill HIV hiding in reservoirs). In fact, Balagopal believes researchers can now confidently focus on a much easier objective. “I think this means we should redouble our efforts to target the known reservoir, which is the T cell reservoir,” he says. “No doubt, without somehow neutralizing that reservoir, we won’t be able to get to a cure.”

Balagopal says the discovery should also positively impact current drug trials. “It’s thinking about current therapies that are in trials on the way to cure HIV,” he explains. “There’s been less good news when it comes to the cure, but this could be a silver lining… We went in trying to find reservoirs in microphages, but not having found it, I think it’s reassuring more than it is disheartening.”

“We know our immune system is going to be a key partner in getting to a cure,” Balagopal concludes, “and so it’s possible these cells that have inert pieces of virus may have enough pieces of HIV that they misdirect the immune system — so that still needs to be sorted out.”