HIV cure: From pipe dream to promising

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HIV cure: From pipe dream to promising

A longtime activist offers cautious optimism on the eve of HIV cure conference

Aug. 13, 2015
Hope for a cure

At the second annual Conference on Cell and Gene Therapy for HIV Cure at Fred Hutchinson Cancer Research Center, researchers and activists offer cautious optimism for a cure (of some kind) in the not-too-distant future.

Illustration by Kimberly Carney

Recently, Jeff Sheehy — a longtime gay civil rights and HIV/AIDS activist in San Francisco — had a conversation with a 23-year-old man who had just learned he was infected with HIV.

“I said to him, ‘Take your medications. Take care of yourself,’” Sheehy said. “‘You have so much opportunity as a gay man. You can get married. You can have a family. When I was your age, that wasn’t possible.’”

And then he told the younger man this: “We will be able to cure HIV for you. In your lifetime, you will be cured.”

Sheehy, now 58, felt far less hopeful when he received his own HIV diagnosis in March 1997.

“At the time, I was crossing my fingers that I would survive,” he said in a recent phone interview from his home in San Francisco before leaving for Seattle to attend the 2015 Conference on Cell and Gene Therapy for HIV Cure being held today and Friday at Fred Hutchinson Cancer Research Center.

His diagnosis came eight months after studies showed that combination antiretroviral therapy could control HIV. The drug cocktail turned out to be one of medicine’s great success stories, commuting infections like Sheehy’s from a death sentence to a chronic, manageable disease.

And curing HIV — which less than a decade ago was considered so unlikely it was not even a serious candidate for research — is now the focus of a conference drawing community advocates, students and many of the nation’s leading scientists working on HIV. Nobel laureate Dr. David Baltimore, who has made major contributions to both HIV and cancer research and is now working to develop gene therapy cures for both, will deliver the keynote talk this morning.

Jeff Sheehy

Gay civil rights and HIV/AIDS activist Jeff Sheehy

Photo courtesy of Jeff Sheehy

As a governing board member of a voter-created California agency that funds stem cell research, Sheehy is bullish on the conference’s focus on cell and gene therapy to cure HIV. At the same time, he is practiced at weighing hope against hype, regularly reviewing grant applications proposing cutting-edge therapies for a host of deadly diseases. In addition to his personal experience with HIV, he is the longtime communications director for the AIDS Research Institute at the University of California, San Francisco and serves on numerous advisory boards for HIV groups.

So while Sheehy believes a cure in the younger man’s lifetime is possible, he is more measured when it comes to his own.  

“The science is exciting. The work is tremendous. It’s a very achievable goal,” he said. “But realistically, it’s going to take time.”

Timothy Ray Brown: Proof that a cure is possible

Baltimore, president emeritus of the California Institute of Technology, kicked the conference off Wednesday night by taking part in a public forum for an audience that included many HIV/AIDS activists — among them Timothy Ray Brown, who inspired current research efforts when he became the only known person considered cured of HIV.

That first cure was not easy. The Seattle-born Brown received a blood stem cell transplant in Berlin in 2007 to treat acute myeloid leukemia. His German doctor, Dr. Gero Hütter, decided to try to also cure Brown’s HIV infection by finding a stem cell donor who carried two copies of a gene mutation known to confer natural resistance to the virus. He has not taken antiretroviral medication since his transplant.

Efforts to replicate his cure in other HIV-positive patients with leukemia have failed to show the same results, in part because many of the patients died from the cancer or the transplant before it could be determined whether their HIV was gone. Physicians agree that a risky stem cell transplant is only appropriate for people who face a life-threatening cancer in addition to having HIV.

Still, Brown’s case, published in the New England Journal of Medicine in 2009, showed for the first time that a cure was possible. Baltimore and other scientists, including researchers from the Fred Hutch–based consortium defeatHIV, are using Brown’s cure as a blueprint to develop a new kind of therapy that takes an HIV-infected person’s own cells and knocks out or disables the gene, known as CCR5, that acts as HIV’s doorway to cells, mimicking the genetics of someone who has natural resistance. The modified cells are then returned to the patient.

Research teams are looking at different approaches for altering CCR5. Some are modifying T cells, the specialized immune cells HIV targets. Baltimore and Hutch stem cell transplant researcher Dr. Hans-Peter Kiem are each working on modifying hematopoietic stem cells — the precursors that generate all the specialized cells of the blood and immune system, including T cells.

Kiem just opened a clinical trial for patients undergoing chemotherapy for AIDS lymphoma, a common cancer in people with HIV-suppressed immune systems. His team will collect patients’ blood stem cells, modify them to make them resistant to HIV and reinfuse them after the last cycle of chemotherapy. The goal is to get enough HIV-resistant cells thriving in the patients’ bodies to mount an immune response to control the virus without daily pills.

Even short of allowing people to go off medication, cell and gene therapies have already shown some intermediate benefits. A 2010 clinical trial in San Francisco that removed, altered and returned T cells to a group of people who were able to control the virus with drugs but were left with weakened immune systems got a still-lasting boost, relieving them of regular bouts of pneumonia and other opportunistic infections.

Noted Sheehy, “This may be a bunt single, but it counts.”

What they mean when they talk about cure

When combination antiretroviral therapy was first introduced in 1996, some had hoped that it would lead to cure in everyone. Scientists have since learned that reservoirs of latent HIV-infected cells hide in the body, out of reach of the drugs. Stop taking the once-a-day pills, and the virus comes roaring back.

Today, HIV researchers talk about two kinds of cure. One — the holy grail of cures — is called a “sterilizing cure,” in which the virus is completely eradicated from the body. That is what Brown is believed to have. They also talk about a “functional cure” in which latent HIV remains in the body but is kept in control without daily medication.

At Wednesday night’s public forum, Brown rose from the audience to ask how Baltimore came down on which type, if either, is possible. “I would like to know your position on if HIV is curable,” he said.

“I believe you are cured,” Baltimore replied. But as to whether a sterilizing cure could be applied more broadly, he added, “I’m agnostic.”  

To Dr. Paula Cannon, a University of Southern California stem cell expert who also spoke at the forum, a functional cure could do the job, but it needs to do more than suppress the virus without the need of a daily pill. An HIV infection is a massive assault on the immune system that can have lifelong consequences, even if a person takes antiretroviral drugs, she said.

“That’s what cell and gene therapy can bring to the table,” she said. “It can help arm the immune system against the stowaway in the body and rewind the clock back to the state the immune system was in before a person was infected. We can get there whether we get all of the virus out of the body or not.”

‘If you can shut down the virus, why wouldn’t you do it?’

Why talk about a cure of any kind when antiretroviral therapy has been so successful? Because not everyone can tolerate the drugs and not everyone has access to them or takes them regularly. Even in the United States, less than 40 percent of the 1.2 million people infected with HIV are on antiretroviral drugs, and just 30 percent have achieved viral suppression, leading to better health, longer lives and less likelihood of transmitting the virus, according to the Centers for Disease Control and Prevention.

Then there is the expense and effort of treating people for a chronic illness for the rest of their lives. And finally, even for those with well-suppressed HIV, who, like Sheehy, have been on antiretroviral drugs for years, the virus continues to do damage by causing low-level inflammation that increases risk of heart disease and cancer.

“Even well-controlled virus doesn’t give you the same level of health that you would have otherwise,” said Sheehy. “When you’re talking about the 23-year-old guy I was talking to, that’s going to have an impact on his life. If we can get a cure for him, that will make a difference. If you can shut down the virus, why wouldn’t you do it?”

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Mary Engel, a staff writer at Fred Hutchinson Cancer Research Center, formerly covered medicine and health policy for newspapers including the Los Angeles Times, where she was part of a team that won a Pulitzer for health care reporting. She also was a fellow at the year-long MIT Knight Science Journalism program. Reach her at mengel@fredhutch.org.

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