Researchers from many corners of the world, including the Nobel Prize winning co-discoverer of the AIDS virus Françoise Barré-Sinoussi, are in Seattle this week to explore the possibility of curing people of HIV.
It’s the right place for such an ambitious meeting, given that the first person to ever be cured of HIV infection is a former Seattle man, Timothy Ray Brown, who for many years remained anonymous as the Berlin patient - so-called because he was cured in Berlin. Brown’s cure came from a stem cell (aka bone marrow) transplant, a treatment given him for acute myeloid leukemia.
“But he was also cured of the HIV infection because the donor’s stem cells included this genetic mutation (that prevents HIV from invading cells),” explained Hans-Peter Kiem, who with Keith Jerome runs the Defeat HIV cure research program at the Fred Hutchinson Cancer Research Center. “This left Timothy Brown free of HIV and led the National Institutes of Health to launch an enormous new effort aimed at finding an HIV cure.”
The Seattle team received $20 million from the NIH in 2011 to pursue an approach built on the many decades of work and expertise at Fred Hutchinson devoted to improving cell transplantation methods, immunotherapy and, more recently, finding an effective vaccine against HIV.
Many people know the center pioneered bone marrow or stem cell transplantation. But some may not know Fred Hutch is also home to the world’s largest international HIV vaccine clinical trials network, which was built on the research center’s deep roots in immune system science.
So how close are we to finding a cure for HIV, for AIDS? Not very, at least when it comes to the traditional concept of a disease cure.
“If we are talking about about eradication (of HIV, as in Brown’s case), I doubt we will reach this objective,” said Barré-Sinoussi.
The transplant approach taken to cure Brown was difficult, dangerous, expensive, somewhat accidental (since curing him of his cancer was the primary mission) and extremely limited in application since it depends upon using only donors with the specific gene mutation that inhibits HIV cell infection. And other aggressive approaches intended at totally eliminating HIV, such as for the so-called Mississippi baby, have not led to a complete cure.
It’s not always clear why some of these approaches fail, but in general it is due to the AIDS virus’ ability to hide within tissue and cells – reservoirs, the scientists call them – avoiding the various drugs or other therapies aimed at finding and killing HIV.
But when it comes to a ‘functional cure,’ Barré-Sinoussi said, there is real hope and promise. By functional cure, she means something to what many cancer patients know as ‘remission’ – the absence of cancer in the body.
“In cancer, we talk about remission for five years and after that we slowly, carefully, start using the word ‘cure,’ said Kiem.
“I believe that this, a functional cure for HIV, is possible,” Barré-Sinoussi said. As a scientist, she said she would prefer to call it by the more accurate and tentative term ‘remission,’ but she said the media prefers to talk of it as a cure.
And an HIV cure of some kind is also absolutely necessary, Barré-Sinoussi added, since today there still tens of millions of people who could benefit from the anti-retroviral (ART) drugs that prevent death and disease from HIV who are not receiving the drugs. Long-term drug therapy for everyone with HIV is unlikely to ever happen, or be sustainable, she said.
The hope for a functional cure of HIV comes not just from the Timothy Brown case. There are people (many of them sex workers), known by scientists as the non-progressors, who are infected with HIV but never get ill. That indicates there is some kind of immune response that can keep HIV at bay. There are also a group of patients Barré-Sinoussi works with, known as the Visconti cohort, who were aggressively treated early for their infection and then taken off the ART drugs – yet have remained free of HIV for nearly a decade.
“So we have these proofs of concept,” she said. “The challenges are enormous, but I believe a cure is possible.”
Kiem said the goal of the Seattle meeting is to bring scientists together who come at the challenge from many different angles. Some are working on better understanding how HIV hides in the body, he said, while others are focused on figuring out what is working – and what isn’t – in the immune response to HIV. Some, like Jim Kublin and his team at the HIV Clinical Trials Network, are researching multiple avenues of inquiry in the search for an effective HIV vaccine.
The team led by Kiem and Jerome are focused on finding a gene therapy, or cell therapy, approach to curing people of HIV based largely on what’s been learned since Brown was cured. But science seldom progresses in a straight line and new insights often arrive from the most unexpected sources.
“Ultimately, what we are all trying to do is boost the immune system,” Kiem said. “For HIV, treatment and prevention overlap. The work being done by those working on a vaccine for prevention can lead to new insights for treatment. It’s all about immunity so it makes sense to get everyone together in the same room.”