People who acquire HIV can lose a critical function in their body: their immunity. Left untreated, HIV infects the immune system and disables a person’s ability to fight infections, which can turn the common cold into a death sentence. Antiviral treatment can prevent this from happening, but if medications are stopped the virus comes back almost immediately.
Currently, one out of every 200 American adults lives with HIV. As doctors, scientists and advocates gather in South Africa this week at the, researchers at Seattle Children’s have been thinking hard about how to kick HIV, and they have an ambitious goal: They want to develop an immunotherapy that harnesses the power of the immune system to kill and resist HIV.
“Immunotherapy has been successful in treating cancer and we’re optimistic that we can take that same technology and apply it to HIV,” said Dr. Thor Wagner, an infectious disease specialist and pediatrician at Seattle Children’s Research Institute. “The hope is that in the future we’ll be able to take an HIV-positive person’s T cells and re-engineer them to attack and resist the virus.”
Growing up and living with HIV
Tranisha Arzah, 26, has a cheerful laugh and bright brown eyes. She likes to dance, travel and hike. She is young, but she has already lived through a lot: She was born with HIV and lost her biological mother and brother to the disease. Today, she works at the BABES Network as an HIV advocate and educator.
While historically HIV has not been a condition associated with children, about 25% of new HIV infections in the U.S. are in youth ages 13-24, according to the U.S. Department of Health and Human Services. Children also have to bear the burden of the disease longer than those infected as adults.
While being a child with HIV could be hard, Tranisha found being a young adult with HIV was even more difficult. She was seen by Dr. Ann Melvin at Seattle Children’s throughout her childhood.
“When I was young my parents managed my healthcare,” Tranisha said. “I just knew I was sick and had to take medicine. It wasn’t until I was 18 that I realized I had to start managing everything myself and it was a lot to take on.”
While HIV drugs work to suppress the virus, staying healthy requires careful adherence to a drug regimen and checkups. Tranisha says it can be hard for teenagers and young adults to keep up with it all.
“When I moved to Bellingham after graduating from high school, it was incredibly stressful being in a new city by myself without my network and mom helping me manage my medications every day,” she said. “Things like insurance changes, medical forms and scheduling appointments could get overwhelming. It wasn’t until I moved to Seattle two years later when I found a network of women living with HIV that the struggle began to shift.”
Dr. David Rawlings, director of theat Seattle Children’s Research Institute and Wagner’s collaborator, echoes this sentiment.
“We were inspired by young patients in our hospital who carry the lifelong burden of chronic illnesses,” Rawlings said. “We want to find better treatment approaches, and we believe immunotherapy may be key to addressing these challenges.”
Re-engineering the immune system
HIV destroys the immune system by entering, killing and replicating inside a person’s T cells, which are white blood cells in the immune system that are crucial to fighting infections.
Rawlings and Wagner want to outmaneuver HIV by using gene editing in T cells to both attack and resist the virus. Their approach uses chimeric antigen receptor (CAR) T cells, which have been effective in treating leukemia in the Seattle Children’s Pediatric Leukemia Adoptive Therapy (PLAT-02) clinical trial.
“If you think about a T cell as a house, HIV uses a couple of keys to get in,” Wagner said. “With gene editing, we can change the locks and block HIV from getting into the T cells. Simultaneously, we give the T cells a key of their own to unlock and destroy other T cells that are infected with HIV.”
Wagner, an assistant professor of pediatric infectious diseases at the University of Washington, says the ultimate goal of the research is that some day they could develop a more effective treatment for HIV that would involve collecting T cells from a patient’s blood, editing the cells in a lab, and then reinfusing them back into the patient where they would seek out and kill HIV-infected cells. He and Rawlings are working on refining the gene editing process so that the engineered T cells will also to be resistant to HIV.
Rawlings, a professor of pediatrics at the University of Washington, Wagner and their colleagues have already made major advances in editing T cells by manipulating their genes to give them HIV-resistance and killing functions. For more scientific background on this technique, read “Seattle Children’s Researchers Pioneer Gene Editing That Kills, Resists HIV.”
Living in the present, looking ahead for better treatment
Tranisha is far from unique in living with HIV: According to the U.S. Department of Health and Human Services, more than 1.2 million people in the U.S. have HIV. Globally, the condition is more devastating with up to 40 million people living with HIV or AIDS, many in parts of the world where treatment is not readily available.
Tranisha mentors HIV-positive teens and is a camp counselor. She says even though modern drugs and treatment have come a long way, it is still a chronic disease and carries significant stigma.
“Being in advocacy and education has given me more confidence in not feeling shame or guilt about having HIV,” she said. “I know a lot of people struggle with this shame, especially women and people of color, but it’s important to not let HIV define you.”
Tranisha is hopeful about the potential that science holds to improve HIV treatment for people around the world.
“In the last 20 years, we have come a long way in the U.S. in improving treatments, access to care and communication between those affected by HIV and the medical world,” she said. “While we still have a ways to go, I’m eager and excited about the years ahead for HIV research.”
- Dr. David Rawlings, Seattle Children’s
- Dr. Thor Wagner, Seattle Children’s
- Infectious Disease and Virology, Seattle Children’s