Matt Sharp is no scientist. But when he joins researchers from around the country tomorrow for a conference on using gene therapy to cure HIV, he will bring a perspective that few others in the room can match.
Sharp, 58, has been living with HIV since 1988. He is one of the activists who, early on, worked to make sure that people like him have a seat at the research table, as they will at the two-day Conference on Cell and Gene Therapy for HIV Cure at Fred Hutchinson Cancer Research Center.
“People who are going to be benefitting from the therapies should be at the table when the decisions are made, which is what people with HIV have said from the very beginning,” Sharp said in a phone interview last week from his home in San Francisco. “We demanded it at first. We made it happen. Now it’s become where if the community is not there, there’s something really wrong.”
“It’s critical that people who are affected by this type of research are closely involved and can give us feedback,” he said.
Kiem and Dr. Keith Jerome, an expert in viral infections at the Hutch’s Vaccine and Infectious Diseases Division, lead a public-private consortium of researchers investigating using genetically modified stem cells to cure HIV. Called defeatHIV, it is one of three distinct approaches to cure research funded by the National Institutes of Health and named the Martin Delaney Collaboratories — after a prominent AIDS activist and educator. Sharp is national coordinator of the community advisory boards that work with each collaboratory.
What is the norm today was radical in 1989 when activists stormed the fifth International AIDS Conference in Montreal demanding a voice. People with AIDS urged scientists to allow those most affected by the epidemic to help determine acceptable risks in clinical trials. To hold their own in meetings, they learned everything they could about their disease, reviewing the latest research in medical journals and organizing classes.
“People were dying,” Sharp said. “It was a desperate time.”
Back in the day, activists held bake sales and sold T-shirts and buttons to pay for crashing conferences. Today, meeting organizers invite advocates and find sponsors to cover their travel and registration costs. Gilead Sciences and Sangamo BioSciences are underwriting the costs for Sharp and eight other community advisory board members to attend this week’s conference.
The collaboration between activists and scientists has been fruitful.
“I credit patients being at the table with having over 25 antiretroviral drugs approved for HIV right now,” Sharp said. “We’re seeing more and more disease groups trying to educate their own so they can help with clinical trial design, push the effort to get things done faster.”
For Sharp as for so many others with HIV, politics is personal. Diagnosed years before there were effective treatments, Sharp lost two partners to the disease. He credits his survival to participating in clinical trials of experimental drugs.
That is one more perspective that Sharp brings to this week’s conference: He participated in one of the first clinical trials of gene therapy for HIV.
In 2010, Sharp participated in a small clinical trial in San Francisco. His blood was drawn and his T cells were filtered out and genetically altered to mimic a rare gene mutation that confers resistance to HIV. The cells were then returned to his body.
The goal of the trial was simply to see if altering and returning the genes worked and could be done safely. For Sharp, the results were better than expected: His T-cell count, which had been low before, more than doubled and has remained high, relieving him of the regular bouts of pneumonia he used to suffer.
DefeatHIV is investigating a similar approach using genetically modified stem cells—the proginator cells that give rise to T cells and the rest of the immune system. This approach most closely resembles the case that revitalized hope in finding a cure for HIV, that of Timothy Ray Brown. The Seattle-born Brown received a stem-cell transplant in Germany in 2007 to treat acute myeloid leukemia. His German doctor decided to try to also cure Brown’s HIV infection by finding a stem cell donor who carried two copies of the rare gene mutation.
Before the treatment, Brown had been controlling his HIV with combination antiretroviral drugs. Combination therapy, while life-saving, is not a cure. Reservoirs of latent HIV-infected cells hide in the body. If a person stops taking the daily pill, the virus roars back. But Brown has not taken antiretroviral medicine since the stem cell transplant and his virus has not rebounded, giving him the distinction of being the first person pronounced—however cautiously—cured of HIV.
Using Brown’s case as a blueprint, defeatHIV plans to take an HIV-infected patient’s own stem cells and knock out or disable the gene that acts as the HIV doorway, then return the modified cells to the patient.
Sharp said that he is pleased to see an entire conference devoted to gene therapy approaches, a first for HIV research.
“This is the first kind of meeting I’ve been to that is actually highlighting this approach,” Sharp said. Right now we see that people who are doing the ‘shock and kill’ approaches, the immunological approaches, are getting more attention in the scientific field. I want to try to get the appropriate place on the map for cell and gene therapy approaches.”
At 38, a generation younger than Sharp, Paris Mullen will also attend the conference this week as a member of defeatHIV’s community advisory board. He came to HIV activism through his work as an educator and health advocate for communities of color. African Americans are particularly hard hit by the HIV epidemic, accounting for almost half of all new infections as well as almost half of all people living with HIV. Yet bringing black people with HIV to the table has been complicated by historic distrust of medical research dating back to the infamous Tuskegee experiment in which poor black men were used as guinea pigs as scientists studied the effects of untreated syphilis.
Being on the advisory board is “a unique opportunity to walk between the world of scientists and the world of communities not ordinarily connected to or trusting of science,” Mullen said.
One of his goals is to come up with the right language to talk to African Americans and others about a cure for HIV, starting with what the word itself means.
Scientists have said that the most realistic goal may be a so-called “functional cure” that doesn’t necessarily eradicate all traces of the virus but eliminates the need to take daily pills. They are also careful not to raise hopes that a cure of any kind will be widely available any time soon.
It’s crucial to make these points clearly, said Mullen. “If people think cure means eradication and then find [the virus] is not eradicated, they’ll feel they were lied to,” he said.
Mullen hopes to learn more about the science of cure research so that he can explain it to the communities he works with. “Every opportunity we have to make science make sense to lay people is important,” he said.
At the same time, he hopes that his presence reminds conference attendees that their work remains urgent, even if activists are no longer storming the gates.
“People assume that HIV is over,” Sharp said. “We know until there’s a cure, it’s not over. That’s something that everybody at the meeting will certainly comprehend, but I don’t think the larger, global community quite gets that yet.”
The public is invited to hear Nobel laureate Françoise Barré-Sinoussi — who in 1983 co-discovered the virus that causes AIDS — at 7 p.m. Aug. 27 at Fred Hutch’s Pelton Auditorium. Barré-Sinoussi will be the keynote speaker on Aug. 26 at the first Conference on Cell and Gene Therapy for HIV, hosted by defeatHIV, Fred Hutch, the University of Washington Center for AIDS Research and the UW Virology Division.
Mary Engel is a former staff writer at Fred Hutchinson Cancer Research Center. Previously, she covered medicine and health policy for the Los Angeles Times, where she was part of a team that won a Pulitzer Prize for Public Service. She was also a fellow at the Knight Science Journalism Program at MIT. Follow her on Twitter @Engel140.