Dr. Joshua Schiffer (third from left) and E. Fabian Cardozo-Ojeda (far right) led research published on Tuesday that provides mathematical models on strategies for optimizing treatment for HIV. (Fred Hutchinson Cancer Research Center Photo)

In the nearly four decades since HIV was discovered, only two people have been cured of the virus that has killed millions.

Researchers in Seattle are hoping to boost that number. On Tuesday, scientists from the Fred Hutchinson Cancer Research Center and the University of Washington published a study that provides clues to optimizing treatments that could wipe out HIV in infected patients.

Worldwide, some 26 million people are receiving antiviral therapy to keep the virus in check, but the drugs dont completely stamp out HIV, the virus that causes AIDS. The virus becomes latent, hiding out in cells until the drugs are gone. It gets activated again and starts reproducing.

One key component to HIVs reanimation is the presence of a molecule called CCR5 thats found on the outside of a certain class of immune system cells. The CCR5 helps the virus enter and infect new cells.

The two men seemingly cured of HIV, known as the Berlin Patient and the London Patient, also had cancer, one with acute myeloid leukemia and the other Hodgkin Lymphoma. As part of their cancer treatments, the patients received transplants of healthy stem cells, which produce immune system cells. They received the transplants from donors who lacked the gene that produces functional CCR5 molecules.

It appears that by suppressing the virus and then cutting off its pathway to resurgence, the virus can be defeated.

Since the 1960s, the Fred Hutch has been a pioneer in bone marrow transplants in cancer treatment, and researchers there are applying similar strategies for treating HIV.

Fred Hutch and UW scientists in recent years have performed experiments using pig-tailed macaques that are infected with a simian version of HIV. In one study of 22 monkeys, the infected macaques received transplants of their own stem cells, after they were treated to knock out the CCR5 gene. Researchers were interested in using the monkeys own altered cells because their immune systems would accept them and not perceive them as foreign invaders to be fought off.

One of the challenges of this approach to fighting HIV is figuring out how many of the altered stem cells are needed its difficult to produce a massive supply in order to overwhelm the cells that still produce CCR5. Add to that the rate of stem cell replication and figuring out the timing of administering and stopping antiviral drugs.

Thats where the new research comes in.

E. Fabian Cardozo-Ojeda, a senior staff scientist at the Fred Hutchs Vaccine and Infectious Disease Division, took all of the data available from the 22 monkeys to figure out how to perfect the treatment. He and his team developed a multi-stage mathematical model to calculate the effects of different amounts of residual and transplanted stem cells, the HIV viral load and the timing of when antiviral drugs are halted.

Were trying to do interdisciplinary work to get that optimal approach for a cure, Cardozo-Ojeda said.

In order to control HIV through this strategy, the researchers came to two conclusions with their formula. First, a patient needs a dose of at least five times as many transplanted stem cells compared to residual cells, and second, before a patient stops taking antiviral drugs, the cells lacking CCR5 need to total between 76-to-94% of the total transplanted stem cell population in their blood.

While the study was based on macaque data, were generating possible hypotheses of what could happen with people, Cardozo-Ojeda said. When it comes to applying their formula to higher primates, we believe that could be translated to humans for sure.

The peer-reviewed study was published by eLife, a non-profit platform. Cardozo-Ojeda is first author of the study and the other authors are Elizabeth Duke, Christopher Peterson, Daniel Reeves, Bryan Mayer, Hans-Peter Kiem and Joshua Schiffer.

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