Could children be evolving resistance to HIV?

Is the human species developing responses to HIV now that we've been exposed to the virus for more than a generation?

That's the tantalizing hypothesis some scientists are suggesting after a new study has show that 10 percent of children with HIV are nonprogressors. In other words, these children have HIV, but even without treatment they aren’t having the symptoms usually associated with the disease, and presumably won't ever develop AIDS or the opportunistic infections that accompanies it. Scientists are now wondering if this will open the door to new immune-based treatments for HIV — or even a cure.

The new study, released this week in Science Translation Medicine looked at “pediatric HIV patients who have normal CD4 T cell counts, despite high viremia and lack of antiviral treatment.” Despite high viral loads and not being on antiretroviral medication, these children still have the same number of T Cells as healthy children.

Scientists have long known that most monkeys with the simian version of HIV (SIV) don’t have the kinds of symptoms seen in humans. Research teams from Britain's University of Oxford and the University of KwaZulu-Natal in Durban, South Africa, wondered if the same line of defense was shared between the monkeys and these children.

Earlier researchers, including Dr. Warner Greene, a professor of Medicine Microbiology and Immunology at University of California San Francisco, investigated why monkey immune systems seem capable of fighting off SIV, while ours don't do the same with HIV. Greene learned that the monkeys don’t have the inflammatory response that is triggered by HIV in humans.

As Plus previously reported, Greene discovered that when it comes to HIV, human cells aren’t actually killed by the virus, but by our own immune responses. When a person aquires HIV, their CD4 T-cells launch an immune response against HIV that leads to massive inflammation, which in turn causes death for 95 percent of the cells with HIV.

In a study published in the journal Nature, Greene noted that the cells essentially commit suicide in a vain attempt to protect the larger host. Their deaths trigger the immune system to send even more CD4 T-cells, which repeat the cycle. Calling this “death by friendly fire,” Greene says HIV turns our own cellular defenses against us, causing the greatest number of CD4 T-cells that die in an HIV infection to be killed by this cell "suicide," not “viral murder.”

In the latest study, researchers observed that pediatric nonprogressors shared two immunological aspects seen in monkeys: low immune activation despite high viremia, and low CCR5 expression in long-lived central memory CD4 T cells. The CCR5 protein plays a central role in HIV's ability to attach to cells.

Many of the children in the study had viral counts of over 10,000 copies of HIV in every milliliter of blood. Normally, this would have trigged an immune response, which would have led to the cell death cycle that Greene described, and/or those children would become very ill. But neither of those things happened.

A researcher involved in the new study, Dr. Philip Goulder from the University of Oxford, told the BBC: "Essentially, their immune system is ignoring the virus as far as possible."

This is different from how elite controllers — a small group of individuals who are HIV-positive but asymptomatic — respond to HIV. While they also maintain high CD4 counts, elite controllers have low viral counts, unlike these children; and the way their bodies react to the virus is also different: elite controllers' immune systems control the HIV virus, these children's immune systems ignore it. 

Most vaccines in the works rely on helping the immune system develop antibodies to HIV, which is kind of like building up a better and better army to face the virus. But these kids' immune systems are laying down their arms and turning their backs on HIV.  It's an approach different from anything we're seeing in other people, but it is similar to what we see among monkeys in regards to SIV.

So is this evolution? Monkey resistance to SIV occurred through natural selection over thousands — or possibly millions — of years of coevolution (monkeys and the virus). The mechanism that developed in monkeys during those thousands of years “is very similar to the one in these kids that don't progress," Goulder said.

The researchers believe their subjects reflect 10 percent of children with HIV.  As a whole, children have less reactive immune systems than adults (which is why things like chickenpox are more severe in adults). This may also be why there have been a number of reportedly “cured” HIV-positive children, who later developed HIV-related symptoms as they got older. 

Commenting on the study, Dr Ann Chahroudi and Dr Guido Silvestri from Emory University speculated that researchers could have uncovered the "very earliest signs of coevolution of HIV in humans."

Because of the potential for the immune system to change during adolescence, the Emory professors still caution: "It is not known whether it would be clinically safe for these newly-identified HIV-infected pediatric non-progressors to remain off-therapy. This assessment is further complicated by the fact that prevention of HIV transmission to sexual partners becomes relevant in adolescence."  Scientists fear that those nonprogressors could still potentially transmit HIV to others.

Goulder, too, believes his team's latest study could open new doors for treatment — or even a cure. 

"We may be identifying an entirely new pathway by studying kids that, in the longer term, could be translated to new treatments for all HIV infected people,” he told the BBC.