Will a so-called "functional" cure be enough to keep HIV in check

JOHN-MANUEL ANDRIOTE - www.theatlantic.com
As scientists and advocates push beyond merely managing HIV infection with expensive and toxic prescription medications, an overarching question is: Will a so-called "functional" cure be enough to keep HIV in check, such that people with the virus can go months between medical treatments? Or is a truly "sterilizing" cure -- a complete and provable eradication of all traces of HIV -- the only goal worth pursuing?



Dr. Robert C. Gallo, the renowned microbiologist who, in 1984, proved that HIV is the cause of AIDS, recently reflected on what is meant by a functional cure and why he believes only a sterilizing cure will ultimately put HIV out of business.

"It's very important to define our terms," said Gallo. "A functional cure generally means people are living a reasonably normal life, maybe a completely normal life. They still carry some evidence of virus, very low, not doing any damage, at least undetectable damage. But they still take their drugs. This can be regarded as a 'cure,' a cure in quotes." He said that to the extent that antiretroviral therapy can manage HIV infection, "I'd say we already have a functional cure."

But what kind of cure is it when people still have to take drugs?
"Can we reach a state where you don't need drugs, where there is no damage from residual virus?" Gallo asked.
Gallo is skeptical about the claim that the so-called "Berlin patient," Timothy Brown, was totally cured of HIV. "There is no proof that the so-called Berlin patient has no more virus," he said. "We know many animals, monkeys, that we thought were totally free until they died or the monkey was sacrificed. If you looked in the intestinal tract and the brain, you would find virus sequences. So they weren't totally virus-free."
Gallo said Brown can be said to have a functional cure in that he has tested HIV-negative on standard tests and has not had to take medication for five years. He was "extremely lucky" not to die from his lymphoma or the full-body radiation used to treat it, said the longtime cancer researcher. His doctor was fortunate to find a stem-cell donor who happened to be one of the extremely rare people with the genetically mutated white blood T-cells -- the targets of HIV -- that are able to resist HIV infection.

"It's not relevant to the vast majority of the world," said Gallo of the Berlin patient case. "The feasibility is not high even under the most ideal circumstances to repeat that study anywhere in the world."

The current rage in HIV cure-related research is called "purging." In short, it involves using anti-HIV drugs to "smoke out" the latent virus lying dormant in reservoirs within the body, particularly the brain and gut. Soon after someone stops the medications, the virus is able to be reactivated quickly. In theory, the reactivated virus and the cells it infected will be killed and additional drugs will block new infection of other T-cells.

Gallo's objections to this approach are twofold. "No one has ever proved that once you reactivate the virus, the cells die," he said. "Second, what's the evidence that you completely protect the other cells by using anti-HIV therapy?"
He said the purging concept is not based on proven, sound principles. "I'm not a prophet," he said, "but from what my thinking will tell me, it's not likely to work and could make it worse."

So what does Dr. Gallo -- whose Baltimore, Maryland-based Institute of Human Virology is one of the world's foremost sponsors of clinical and laboratory research on HIV and other infectious diseases -- believe it will take for a true sterilizing HIV cure? And how close are we to having it?
One possible gene therapy approach targets T-cells, knocking out the CCR5 receptor -- the T-cell's portal that allows HIV to enter it. Close the door ,and the virus simply can't get into the cell and is eventually eliminated by the body.

The ultimate solution, said Gallo, would be to get genes into a sufficient number of T-cells so that enzymes can be directed to cut out the HIV genes that have become part of the T-cell's own genetic makeup. "That would give rise to new cells without the virus," he explained. But while the concept is promising, these approaches to a sterilizing cure remain several hurdles from viability.

JOHN-MANUEL ANDRIOTE - The author of Victory Deferred, John-Manuel Andriote has specialized in HIV/AIDS reporting since 1986. His research materials, correspondence, and recorded interviews are part of a special collection curated by the Smithsonian.