Author's note: This week, researchers announced a breakthrough: They’ve cured the second person in the world of HIV, the virus that causes AIDS, via the same method that cured Seattle native Timothy Ray Brown 12 years ago — bone marrow transplantation intended to treat cancer. The results were published in Nature and detailed at this year’s Conference on Retroviruses and Opportunistic Infections (CROI), taking place in Seattle March 4-7. This development adds to the greater body of research moving towards an HIV cure, with Fred Hutchinson Cancer Research Center as one of the leading hubs of that work. It’s important to note that a cure is only as good as access to it, and this is one of a few approaches researchers are exploring, which also includes CAR-T cell therapy and gene therapy, in hopes of finding a scalable cure for those living with HIV.
Growing up in Seattle, Tranisha Arzah knew her family was unusual. “I knew something was wrong from the get-go,” she says, “witnessing what was happening to my surrounding family.” Her mother died when Tranisha was 4 years old and her brother, Tradell, passed away not long after.
By age 7, Arzah had a name for what had killed her mother and brother; they had died of AIDS-related complications. Arzah herself was born with HIV.
She recalls being unsurprised by the news that she had HIV, but shocked and scared by the implications. While child therapists and case managers helped shape her understanding of the disease during her formative years (spent in Port Townsend, Wash., where she lived with the foster mom, who would eventually adopt her), Arzah felt very alone. There were few other African Americans at her school and she knew no one else with HIV. “It took a lot of time to find out what [having HIV] meant in my life,” she says.
Today, at age 27, her social life is that of a typical young adult, and HIV has shaped her career niche. As a peer advocate with BABES Network, a YWCA-based support group for women, Arzah counsels and connects women who have HIV. She also volunteers for the Community Advisory Board (CAB) of defeatHIV, a research group at Fred Hutchinson Cancer Research Center in Seattle funded by the National Institutes of Health and focused on finding a cure for HIV. CAB serves as a bridge between research scientists and the HIV-positive community; as part of it, Arzah and other HIV-positive people counsel scientists on the reality of living with the disease.
DefeatHIV is one of six Martin Delaney research labs in the U.S., all searching for a cure for HIV. Named after an AIDS activist, defeatHIV and two other labs were funded in 2011. A second round of funding came in 2016, adding three more laboratories to the group.
If you haven’t thought much about HIV lately, you’re not alone. While the research community is ramping up research on the disease, much of the non-HIV-positive population has largely put it out of sight and out of mind. That’s partly because of how well-managed the disease is in the U.S. Most people living with HIV take some variation of oral medications. Arzah takes two pills daily, while others take one pill that combines three medications. Others take more. The combination of drugs depends on the person, but the result is the same: suppression of the virus to near-nonexistence.
“There’s been so much advancement in treatment — treatment is now considered a form of prevention,” says Arzah. In other words, treatment prevents the virus from activating and multiplying, which makes the viral load of an HIV-positive person undetectable and intransmissible. That means just what it says: With treatment, HIV cannot be passed on via sexual contact or from mother to child. Bringing that understanding more widely to the public is also the focus of a worldwide effort from Prevention Access Campaign, a global group of advocates, activists and researchers begun in 2016 by a community of HIV-positive people. They refer to it as Undetectable = Untransmittable, or U=U.
Effective treatment has led to a big misconception: that the virus has been cured, or as good as cured. As part of her work, Arzah visits juvenile detention centers and still hears from young girls, “Was Magic Johnson cured?”
Suppression, of course, isn’t a cure. “If a person stops taking the drugs, the virus typically comes back in two weeks or so,” says Dr. Keith Jerome, a virologist who co-directs defeatHIV with Dr. Hans-Peter Kiem, a gene therapy expert. Globally, access to effective treatment is far less reliable. “Remember, there are 36 million people in the world living with HIV,” says Jerome. “In many parts of the world, being sure that you’ll have access to a drug today, tomorrow and next year — and for the rest of your life — is very uncertain and can be a real burden.”
Other misconceptions linger, such as the early-epidemic idea that HIV is primarily a disease among gay men. Worldwide, as of 2016, an estimated 17.8 million women are living with HIV who are age 15 and up, making up 52 percent of all adults living with HIV, according to UN Women. Arzah says that in the past year more women in Seattle — many of them immigrants — have found BABES Network, which is a women-run support network providing information, education, case management and more to HIV-positive women. Additionally, potential for crisis is closer than we think: in August 2018 eight heterosexual drug users were found to have contracted HIV in Seattle.
For those with HIV and those studying it, Washington is one of the best places to be. In 2014, Washington was the first state to create a state-funded assistance program to help HIV-negative people who are at very high risk for contracting HIV through sex or injection drug use, as well as getting access to the prevention pill PrEP (Pre-Exposure Prophylaxis). In addition, the only known person to be cured of HIV, Timothy Ray Brown, lives in Seattle. He sparked Arzah’s interest in finding a cure when he spoke at a Seattle event sponsored by the defeatHIV CAB. In addition, he’s served as inspiration for the scientists at defeatHIV.
Thanks to advancements in knowledge and technology, accelerating the search for a cure is more possible now than ever. “It’s the right time,” says Jerome.
“We came to the realization that we’ve learned so much about the virus,” says the virologist. “At the same time, over the last decade or so, the scientific community has developed this incredible ability to manipulate things within the human body with a degree of precision and control that we’ve never had before.”
DefeatHIV focuses on cell and gene therapy via the “ways that we can manipulate cells so that the body is especially good at fighting off HIV, or even going in to target HIV for destruction,” says Jerome.
Currently, there are three promising approaches the lab has explored. One is evaluating CAR T-cell therapy, used with some types of cancer, in which immune system T-cells are removed from the patient and genetically engineered to produce CARs (chimeric antigen receptors) that will attack virus cells. These are then infused back into the patient, where they can do their work.
Gene therapy is another approach. Here, molecules would be delivered into the body that, as Jerome puts it, “basically sort of soak up HIV and redirect the immune system to get rid of the affected cells. You only need to give them one time, and they’ll be there forever until the virus is gone or it will be suppressed forever.”
The third approach is modeled after what happened in Timothy Ray Brown’s case: removing the receptor for HIV from a patient’s immune cells and then putting them back in the body. In Brown’s case all of the cells were replaced, but the current procedure scales this back so that there is a small population of “gene-protected cells” effectively fighting against the virus, while other cells still have the HIV receptor. “It’s been very effective,” says Jerome. “We’re seeing reductions in virus in the tissues [that are] very dramatic, 10-fold or more, and with really good control. We’re combining that with therapeutic vaccination.”
The lab’s intermediate goal is to optimize each of these approaches over the next few years and then bring them together. “We think that a combined approach, where we’re hitting the virus from all different sides, is really most likely to result in an effective long-term cure,” says Jerome.
But research is just one piece of how defeatHIV works. The advisory board is another. “Our mission is to bridge community and scientists together in achieving the HIV cure,” Tranisha Arzah says. “Scientists might not have the greatest ways of reaching out to community or they might not be doing that. So we invite them to our space and we go to their spaces.”
In each other’s spaces, the two groups talk about research and what the idea of finding and then having a cure means to the HIV-positive community. For example, the group discusses the ethics of research when treatments go to human trial stage. According to Arzah, CAB members make sure scientists “are thinking about all the different things that might come up for someone who might offer [themselves] for research.”
“We talk to those scientists and researchers about that so that they can better understand what it is to be on the other side, to be the guinea pig,” says Arzah. “We just want to be sure we’re all on the same page.”
For scientists, Jerome says, those conversations are invaluable. “It’s a great motivator for us to continue to work as fast and as hard as we can," he says. "It’s wonderful to have people from the community who could be those [trial participants] talk about what their fears are, what their expectations are — things we should be thinking about as scientists.” Concerns range from patient transportation to and from the lab to breaking down the intimidating phrase, “gene therapy.”
Michael Louella, defeatHIV’s community engagement project manager, says that while a cure sounds great, it also comes with complicated feelings.
“People have been told many things over the years that haven’t come true,” Louella says. “After the discovery of HIV in 1984, HHS [Health and Human Services] Secretary Margaret Heckler told us we’d have an AIDS vaccine within two years. Three decades into the epidemic, there still isn’t one. This history of dashed hopes and rash overpromising makes talk of a cure difficult because it leads people living with HIV to ask, ‘Dare I open my heart to hope again?’”
However, the hope does spring eternal. “People are inspired by the idea,” says Louella. A cure, he notes, means freedom. “Freedom from the virus, from taking a pill every day; freedom from so much for people," he says. "Even though there might be skeptics, many people believe we will get to it, but it may not look the way they want it.”
“The biggest challenge is that this is a sneaky virus; nearly everything you throw at it, it has had some sort of response,” Jerome says.
But defeatHIV’s work over the past eight years has him daring to dream as well.
“My personal goal is to see this happen in the remainder of my working lifetime; I may work another 15 years or so. We’re working as fast as we can,” he says. “We don’t have something that we have proven is a definite cure for everybody yet. I’ve become more optimistic over the last two years. The pace of science is really accelerating, and this is before we’ve really started to put these things together into these combination therapies that we all agree are the most likely avenues towards success.”
This story first appeared online at Cascadia Magazine.