Some People Infected With HIV Are Resistant To The Virus. Now Scientists Think They Might Know Why

For most people HIV is a simple, yes/no setup: if you're HIV positive, the only question is when you'll develop full-blown AIDS and the only way to stop it is through the use of antiretroviral drugs that are both highly expensive and come with many unwanted side effects. But for about one percent of people infected with HIV, there's another question. How do they do it?

For those people, dubbed "elite controllers," HIV isn't the life-threatening infection that it is for others. They don't expel the virus from their bodies altogether but they do go into remission, without drug therapy and sometimes for decades.

Obviously, if HIV could be a background problem for everyone infected with it, that would be a massive step forward — especially in areas of the world where access to medical care is sparse and AIDS takes a terrible toll on families. So scientists have been studying "elite controllers" carefully since they first came to light, looking for a way to make their amazing ability transferable.

Elite controllers are usually found in adulthood, but there is a now-famous case of an unnamed French teenager who has apparently been an elite controller since birth. Her identiy has not been revealed, but her doctor, Dr Azier Saez-Cirion of the Pasteur Institute in Paris, says she has had only one major flare-up when HIV virus cells became detecable in her blood with standard tests. Otherwise doctors would assume she was uninfected if they didn't know she had been born infected and use special high-sensitivity tests to detect the low number of HIV cells in her body. 

HIV Immunity: The Story So Far

Previous efforts to transfer controllability from one subject to another have ended in failure, as have other attempts to confer immunity. After a brief period of excitement when a girl in a small experimental trial appeared to have been cured of HIV, an event which would have been the first of its kind, hopes were dashed when she turned out to still be infected with the virus. The girl, from Mississippi, was born infected and given large doses of powerful antitretrovials early in life, and appeared to be HIV free until the age of four, when it was discovered that she was still infected. 

Known as "the Berlin Patient," US native Timothy Ray Brown was given a bone marrow transplant in 2007 from a donor who was an elite controller. Following the transplant, Brown's HIV went into remission and he appears still to be cured entirely of HIV. However, this isn't a method of curing HIV that can be successful worldwide because of the dificulty of finding donors and the huge expense of the operation. The results also don't seem to be repeatable: six other patients who had similar transplants, advised though not carried out by the surgeon who performed Brown's procedure, all died of AIDS. 

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Late last year, doctors announced some success using a gene snipping technique called CRISPR. The technique removes a gene in human cells that codes for a protein on the outside of blood cells called CCR5. It's this protein that HIV uses to access the cell; without it, HIV can't attack the cell and enter it to replicate inside it. In lab experiments gene snipping resulted in about half the tested cells becoming "immune" to HIV attack. 

The Future: Acquired Immunity to Acquired Immune Deficiency?

What really has scientists excited, though, is the work of Dr Xu Yu and her team at the Ragon Institute. The Ragon Institute is a collaboration between Massachussetts General Hospital, MIT and Harvard, set up specifically to study elite controllers. They built on what we already know, which is that the bodies of elite controllers have CD8 T-cells, elements of the immune system, that show a far stronger reaction to the HIV virus then the norm. What wasn't known before was why, but Dr Yu thinks her team may have discovered the answer. 

They found it by infecting colonies of dendritic cells - the immune system's intelligence department, responsible for "teaching" other immune cells which virusses and bacteria to target and how — with HIV. Some of the colonies came from HIV patients, some from HIV patients on antiretrovirals and some from elite controllers.

The Elite Controller Paradox

What they saw was not a different amount of a certain response, but two different responses.

In the cells of elite controllers, the HIV virus was allowed to promulgate itself unchecked, running wild and producing large amounts of genetic material unmolested. But then, when the immune cells did act, they produced comparatively gigantic amounts of antiviral compounds called type 1 interferons. 

Two days later, the differences in the two results were even more startling. In ordinary people immune response was dying down. In elite controllers it was still just getting started. Waves of type 1 interferon were still being pumped out and CD8 T-cells were ramping up production to attack the HIV virus. 

The next stage is to figure out why this happens and what it means. Virologist Sarah Roland-Jones at the University of Oxford says, "t tells us what the difference is in elite controller cells, and it sounds pretty key, but it doesn’t tell us why it happens." She thinks the reason may be that the viral DNA buildup in the cells of elite controllers gives the immune system more information and a clearer target. Whatever the reasons, the outcome is clear: elite controllers' immune systems are able to keep HIV populations so low that they're not just asymptomatic, they're often almost undetectable. By contrast, the immune systems of ordinary people attack the HIV virus early, kill some — and leave a large enough remnant to become infected in the normal way.

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Dr Yu's team is now working on substances they might add to vaccines or drug therapies to trigger the dendritic cells of ordinary people to act like those of elite controllers. If it's possible, it would enable us to defeat the HIV virus right where it does the worst of its damage: in our own immune systems.