Re-engineering stem cells to eradicate HIV in lifelong sufferer

April 19, 2016 | by Letisia Marquez

Aaron Kim Aaron Kim (r) with nurse

Aaron Kim has battled HIV since the moment he entered the world.

Born three months premature in 1983, the second of twins, Aaron needed a blood transfusion to boost his red blood cell count. The nation’s blood supply wasn’t screened for HIV (human immunodeficiency virus) then because little was known about the disease and how it was transmitted. Aaron wouldn’t find out he had the virus until he was 5 years old.

“I kept getting rashes and fevers, but my twin sister didn’t,” Aaron, now 32, said recently. “So they figured I had received it from the blood transfusion, because I got it and she didn’t, and no one else in my family had the virus.”

Because he’s had the virus since he was a baby, Aaron believes he will have HIV for the rest of his life. But a new stem cell gene therapy administered by City of Hope’s Alpha Clinic has given HIV patients such as Aaron a glimmer of hope that they may one day live without it.

Re-engineering stem cell resistance

In March 2016, Aaron became the first HIV patient treated as part of a new clinical trial that will determine if a patient’s own genetically engineered bone marrow cells can safely be used to treat HIV. As part of the trial, which was funded by the California Institute for Regenerative Medicine, City of Hope researchers placed ribonucleic acid (RNA) genes that fight HIV in his stem cells and used a lentivirus to change the CCR5 gene to block the virus’ typical infection pathway. Aaron’s cells were engineered in additional ways to bolster the ability of his immune system to resist and eradicate the virus.

“The stem cell therapy Aaron received is one of more than 20 cure strategies for HIV,” said John A. Zaia, M.D., director of the Center for Gene Therapy at City of Hope's Hematologic Malignancies and Stem Cell Transplantation Institute and the Aaron D. Miller and Edith Miller Chair in Gene Therapy. “It may not cure him, but our goal is to reduce or even halt Aaron’s reliance on HIV drugs, potentially eliminating the virus completely.”

Like Zaia, researchers worldwide are trying to replicate the case of Timothy Ray Brown, the so-called “Berlin patient” whose HIV infection vanished after he received a stem cell transplant for treatment of leukemia. It turned out that the donor's CCR5 gene had a mutation that blocked the virus.

“There aren’t enough donors with that mutation to replicate the treatment on a large scale,” Zaia said. “So we have to artificially create the mutation.”

This means that Zaia and his colleagues need healthy HIV patients, like Aaron, willing to go through the new stem cell therapy. “It’s a wonderful and generous humanitarian gesture on Aaron’s part to participate in this trial,” Zaia said.

Reaching unexpected milestones

Aaron, an emerging entrepreneur and Santa Clarita, California, resident, learned about the stem cell treatment from his doctors at the AIDS Healthcare Foundation in Los Angeles. He said he’s motivated to participate in the trial because he’s battled the side effects of powerful drugs over the years, as well as several diseases that developed as a result of his weakened immune system.

T cells fight off infections, but when white cell counts are low it’s difficult for the body to stave off infections and diseases. The normal cell count for a person who doesn’t have HIV or AIDS is between 500 and 1,500. HIV develops into AIDS when a person’s T cell count drops below 200. Aaron has battled AIDS three times, and he’s recovered each time by taking more, or new, anti-viral drugs.

In 1988, Aaron started to take azidothymidine three times a day. Known as AZT, it was the first drug licensed to fight HIV infection.

“My parents would wake me up at two in the morning just so I could take the medicine,” he said. “The medicine would make my feet feel like they were burning, and I would kick my dad when he tried to wake me up.”

In 2010, Aaron developed Burkitt lymphoma, a fast-growing non-Hodgkin lymphoma, and underwent chemotherapy, which led to remission. He’s also been treated for hepatitis C, which he got from the early blood transfusion.

“I never thought I would live this long,” said Aaron, reflecting on the many health problems he’s overcome. In middle school, he didn’t know if he would live to make it to high school, and when he was in high school he didn’t know if he would survive to have the college experience. There was always another milestone that seemed likely to remain out of reach. But now, he said with a chuckle, “I’ve lived through all this, so I think I can reach at least 60.”

A happy re-birthday

On the day of his stem cell infusion in early March, several nurses and researchers who had genetically engineered Aaron’s cells gathered around to wish him “Happy Re-birthday.” Two weeks after that momentous day, Nitya Nathwani, M.D., assistant clinical professor of hematology and hematopoietic cell transplantation, said Aaron had tolerated the treatment well, with few side effects.

“We are very hopeful that the treatment will work and will know more in the next several months,” Nathwani said. “Even though he’s had a lot of health problems prior to this, he’s had such a wonderful attitude throughout this process. We are grateful to Aaron for helping us advance the field.”

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If you are looking for a second opinion or consultation about your treatment, request an appointment online or contact us at 800-826-HOPE. Please visit Making Your First Appointment for more information.

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