Scientists strategize to stop HIV infections, work toward cure

A hot topic for a big scientific conference convening in Seattle
Dr. Carl Dieffenbach
Dr. Carl Dieffenbach, director of the Division of AIDS within the National Institute of Allergy and Infectious Diseases, heads HIV/AIDS research for the federal agency, part of the National Institutes of Health. He spoke in advance of the Conference on Retroviruses and Opportunistic Infections in Seattle. Photo by Josh Belzman / Fred Hutch News Service

As thousands of researchers from around the globe converge on Seattle for a conference on HIV/AIDS, top health officials in the United States are preparing to launch an ambitious new program aimed at eliminating new infections in the U.S. by 2030.

In advance of the Conference on Retroviruses and Opportunistic Infections, or CROI, which opened today at the Washington State Convention Center, Dr. Carl Dieffenbach, who heads AIDS research for the National Institutes of Health, said that the NIH has the money it needs “to jumpstart the program in this fiscal year” and continue it through the next one.

“We are all in,” he said in an interview Sunday prior to speaking at a workshop hosted by the community advisory board for defeat HIV, a research group based at Fred Hutchinson Cancer Research Center in Seattle. That group, a public-private partnership funded by the NIH, is exploring the use of genetically modified, HIV-resistant blood stem cells as a potential cure for the virus that causes AIDS.

HIV prevention in the US: Scaling up success

Details of the program are expected to be discussed this evening in an opening address at CROI by Dieffenbach’s boss, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which is based within NIH. Fauci, Dieffenbach, and Centers for Disease Control and Prevention Director Dr. Robert Redfield are among the top health leaders who have been quietly developing the program, which was revealed by President Donald Trump in his State of the Union Address last month.

Dieffenbach said the HIV prevention initiative will initially target seven Southern states where HIV infection rates remain alarmingly high, and 48 counties — including Seattle’s King County — hard hit by the epidemic. It will build on the success of programs developed in San Francisco, Washington, D.C., and New York. These local efforts have combined quick HIV testing, immediate treatment with antiviral drugs, and distribution of preventive PrEP pills to uninfected people who are at high risk of exposure to the virus — such as sexual partners of people who are HIV positive. PrEP pills are combinations of the same antiviral drugs used to treat HIV. Taken properly, they can lower the risk of contracting HIV by more than 90 percent.

“The model is: taking what works and taking it to a different scale,” Dieffenbach said.

He is particularly impressed by how Washington, D.C., which has a serious epidemic in its lower income population, was able to lower the number of new infections each year to 350 from 1,400. Antiviral drugs work most effectively over time for patients when HIV infection is caught early, and those who take their drugs every day typically have undetectable levels of virus and cannot pass the virus on to others.

Despite such efforts, declines in HIV rates — even in Washington, D.C. — have stalled recently, according to a CDC report last week. Part of the new initiative will focus on ways to step up efforts to reach those in both rural and urban areas who still are missing out on prevention and treatment programs.

Key players in the new initiative will be the regional Centers for AIDS Research, a national network of research laboratories that includes the University of Washington and Fred Hutch. Each center will have an opportunity to develop and test new ways to deliver HIV treatment and prevention. “That’s what we really need,” Dieffenbach said. “In addition to more, we need better.”

Timothy Ray Brown and his physician, Dr. Gero Hϋtter
Timothy Ray Brown, right, and Dr. Gero Hϋtter, the Berlin cancer doctor who gave Brown a lifesaving transplant that also cured him of HIV. Photo by Robert Hood / Fred Hutch News Service

Curing HIV: The audacious goal

Meanwhile, scientists at Fred Hutch and other institutions continue to explore ways to set a distant, yet even more audacious goal: to not just to stop HIV infection but cure it.

Sitting in the audience of the daylong Seattle workshop was Timothy Ray Brown, who remained — at that moment — the only person on Earth deemed to have been successfully cured of HIV.

[On Monday, word leaked that a second patient, treated with a blood stem cell transplant for Hodgkin lymphoma in London, is now likely to be the second person ever to be cured of HIV. The unnamed patient received stem cells from a donor carrying HIV resistance genes and has shown no signs of infection since he stopped taking antiviral drugs in September 2017.] 

Efforts at Fred Hutch and other institutions to cure HIV by clearing out all traces of the virus have been inspired greatly by Brown, an HIV-positive man with leukemia who received two blood stem cell transplants to successfully cure his cancer — 12 years ago. A Seattle native, he was living in Berlin at the time, and his doctor sought out stem cell donors who carried a rare genetic mutation that naturally confers resistance to HIV.

Remarkably, the strategy worked, although up to now, only for him.

“I’ve been saying from the beginning that I have been doing this because I would like more people to join my ‘family,’" Brown said.

Dieffenbach’s talk focused on two approaches to curing HIV. One is to find ways to eradicate the last traces of HIV in the body. Brown’s transplant from a donor who carried two copies of the HIV resistance gene — from mother and father — is one example of that. Another way is to genetically engineer a patient’s immune cells to include those resistance traits — the kind of work underway at Fred Hutch.

A second approach is to focus on ways to give patients what he called “remission in absence of eradication.” In this case, the patient’s own immune system could be trained to block HIV whenever sleeping HIV-infected cells awaken and begin shedding virus. This might be accomplished through injections of HIV-blocking antibodies, like those being tested in vaccines.

“A therapeutic vaccine remains in some ways a holy grail,” he said. “The fantasy is to elicit a profound immune response that continues to drop DNA levels of virus present in an individual.”

In a series of lectures, speakers outlined other efforts to find a path to a cure:

  • Dr. Joshua Schiffer from Fred Hutch described an approach that uses a low-cost, readily available immunosuppressant drug to slow down proliferation, the natural way immune cells increase their numbers. The drug, called mycophenolate mofetil, is normally used in transplants to prevent donated immune cells from attacking healthy tissues of the patient. In a small trial with HIV-positive patients, Schiffer’s team is testing whether it can knock down the proliferation of immune cells that might be harboring HIV genes from earlier infections. Stop the increase of these cells, and the inventory of those containing HIV genes would eventually die out, the thinking goes.
  • Dr. Monique Nijhuis, of the University Medical Center of Utrecht, the Netherlands, described how European doctors have amassed a list of 22,000 potential stem cell transplant donors who carry HIV-resistant genes, like those received by Brown. That has enabled them to continue to test transplantation to eradicate HIV. The European consortium is analyzing the results of 39 patients who have received such transplants, 26 of whom are still alive.

One way or another, researchers are looking for a way to keep HIV at bay without the need for a lifetime of antiviral drugs. In other words, they want more Timothy Ray Browns.

During his talk on HIV cure research, Dieffenbach described the workshop as “an homage” to Brown. “There is still so much we can learn from Timothy and his case,” he said.

“For patients like Timothy, with cancer and HIV, cancer is the worst of the two,” Dieffenbach added. “His leukemia required a sledgehammer-like approach to get through his lethal cancer. … Congratulations, Timothy. It’s great to have you here on your 12th anniversary.”

[Editor's note: This story has been updated to reflect breaking news on March 4 that a second HIV-positive patient who received a blood stem cell transplant for cancer appears to be cured of HIV, 12 years after Brown went off antiviral medications.]

Sabin Russell is a former staff writer at Fred Hutchinson Cancer Center. For two decades he covered medical science, global health and health care economics for the San Francisco Chronicle, and he wrote extensively about infectious diseases, including HIV/AIDS. He was a Knight Science Journalism Fellow at MIT and a freelance writer for the New York Times and Health Affairs. 

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