For a few exuberant months, Gary Steinkohl thought he had become only the second person in the world cured of HIV.
In March 2013, as part of a carefully monitored research study at Boston’s Brigham and Women’s Hospital, he stopped taking the daily antiretroviral drugs that suppress HIV.
The goal was to see whether the two bone marrow transplants that he had undergone to treat non-Hodgkin lymphoma and myelodysplastic syndrome had cured him of his HIV infection, just as a similar — though not identical — treatment for leukemia led to the one known HIV cure, that of Timothy Ray Brown.
Steinkohl distinctly remembers the day he stopped taking the medication. He was by himself in his apartment in New York City, where he has lived all his life.
“I have a visual memory — there’s the drawer in my kitchen where I keep my meds. And I’m not going to take them,” he said in a recent telephone interview. “It was one of those bellwether moments, and it was like, ‘OK!’”
How big a deal was it to interrupt antiretroviral therapy? Scientists have learned that one of the barriers to finding a cure for HIV is that reservoirs of dormant infected cells hide in the body. Stop taking a daily pill and the virus comes roaring back — sometimes resistant to the very drugs that had controlled it before.
But weeks and then months passed, and regular blood tests found no signs that the virus was back. Steinkohl began to think, “I’m going to be the one.”
Then, almost eight months after he stopped taking the meds, his hopes were dashed.
Steinkohl, along with Dr. Timothy Henrich, who led the Boston study, will appear at Fred Hutchinson Cancer Research Center’s Pelton Auditorium Wednesday to talk about what it was like to be “Patient B,” one of two so-called “Boston patients” who stopped taking antiretroviral medication after transplants and what he — and science — learned from the experience. The 7 p.m. event, which is free and open to the public, is hosted by the defeatHIV Community Advisory Board on the eve of the third annual Conference on Cell and Gene Therapy for HIV Cure Thursday and Friday at Fred Hutch.
Until Brown’s case, no one believed HIV could be cured at all. Even now, no one is certain his cure can be duplicated.
The Seattle-born Brown was diagnosed with HIV in 1995 and kept it under control with antiretroviral therapy. Then in 2007 and again in 2008 he underwent bone marrow transplants as last-ditch efforts to cure acute myeloid leukemia after chemotherapy failed. His doctor in Berlin, where Brown was then living, decided to try to cure both diseases at once by finding a bone-marrow donor who carried a rare gene mutation that confers natural resistance to HIV. The hope was that this transplanted immune system would wipe out any hidden pockets of virus in Brown.
He required a second transplant after the cancer returned, but he has not taken antiretroviral medicine since the first, and today he still has shown no signs of either leukemia or HIV.
No one considers stem cell transplants appropriate for the vast majority of people with HIV. They are expensive, risky, last-resort treatments even for cancer patients. (Brown himself barely survived his second transplant.) Still, researchers have been interested in seeing if his cure could be repeated in other patients with HIV and cancer who need a transplant anyway.
Because people with two copies of the HIV-resistant gene are rare — and finding one who would also be a good bone-marrow match would be harder still — scientists at Fred Hutch and elsewhere are investigating using genetically modified stem cells to achieve a long-term HIV remission.
But researchers also are looking at what role the transplant process itself might have played in Brown’s cure, and whether he really needed that HIV-resistant donor. Could the pre-transplant “conditioning” he underwent — the intense chemotherapy and radiation regimen that destroys the immune system to make room for transplanted immune cells to grow — have affected his HIV reservoir? What about the graft vs. host disease he developed afterward, which is known to play a role in curing leukemia: could it have helped destroy the HIV reservoir?
That’s why Henrich, then at Brigham and Women’s Hospital, now at the University of California San Francisco, was interested in finding people like Steinkohl who had undergone a bone marrow transplant, even if their donors didn’t have the HIV-resistant gene. What could researchers learn from them about the HIV reservoir? How much would the reservoir need to be reduced to achieve a long-term remission or cure?
Steinkohl learned he had HIV in 1985, a decade before treatment turned it from a death sentence to a chronic disease. He was 27 and already launched in a corporate banking career. So much for feeling invincible. Instead he spent those awful early years burying friends and wondering why he stayed healthy.
Then in 2003, he developed a type of non-Hodgkin lymphoma found in unusually high rates in people with HIV. Chemotherapy bought him two years, but when the cancer returned in a more aggressive form, he endured a bone marrow transplant in 2006. In 2010, he had a second, less grueling transplant using his own blood stem cells to treat myelodysplastic syndrome, a bone marrow disorder that can progress to leukemia.
Facing death four times over would be enough of a roller coaster for most people. But in 2013, with his cancer at bay and his HIV under control, Steinkohl volunteered to get back on what would turn out to be — emotionally — the wildest ride of all.
He first heard about Henrich’s study from his oncologist on a checkup visit two years after his second transplant. He was immediately taken by the Boston researcher’s gregarious personality and infectious humor. He was impressed by how seriously Henrich took the risks of going off the anti-HIV drugs. But Steinkohl understood that he would do so under careful supervision and would immediately go back on treatment at the first sign that the virus was rebounding.
So talking it over with his sister and only sibling, who had been the bone-marrow donor for his first transplant and who had cared for him afterward, he willingly signed up.
“I don’t think it was so much for my own personal advancement as for our community and a larger sense the world,” he said. “I’d survived all my experiences. I felt I could live a good life and a long life, having been through what I’ve been through, without participating. But due to the uniqueness of my scenario, this is what I wanted to do.”
Every week after he stopped taking his meds, Steinkohl went in for a blood test to check for the virus. “I have been stuck more than a pin cushion, and I still don’t like it,” he said. “They would say, ‘We need another 16 vials,’ and I would be like, ‘Are you kidding me?’ But it’s what you do.”
He confessed to feeling tremendously hopeful, even as he tried to contain his expectations. He only told his immediate family and closest friends what he was doing.
Steinkohl knew there was another patient in the Boston study — Patient A — but because of confidentiality rules, he knew nothing about this person. (Patient A has remained anonymous.) Still, he felt a bond. So when he learned that the virus had returned in Patient A after three months, he felt emotionally deflated. But Henrich explained that their circumstances differed somewhat — Steinkohl’s sister, for example, had been a better match than Patient A’s donor.
Steinkohl had heard about other people with HIV who had taken unsupervised “drug holidays.” In most, the virus had returned within a few weeks and in all by the fourth month. Once he passed that mark, he began to feel different. No one told him he was cured. Henrich remained cautious. But Steinkohl began to conceive of himself as HIV-negative.
It felt shockingly good.
“Over the subsequent couple of months, there was an awe in me that is indescribable,” he said. “I was born HIV-negative, became HIV-positive, and now I’m HIV negative again. It was overwhelmingly wonderful, and in some sense scary. I would be walking on the street and I’d be looking at hundreds of people and thinking, ‘I’m different from every one of them.’ It was emotionally intense in a way I could never tell anyone.”
Weeks passed. The team of clinicians held their breaths every time the test results came back. So did Steinkohl.
Then, in late October 2013, he felt like he was coming down with the flu. He told himself it was the flu or maybe Lyme disease. He took himself to an emergency room in the middle of the night and asked for Lyme and HIV tests.
A nurse from the hospital called the next day: Almost eight months after going off treatment and just a week after he had last been tested at the research site, he now tested positive for HIV.
Under Henrich’s supervision, he went back on medication. It took months for the virus to be brought under control. But Steinkohl approached the challenge with his usual determination. “It was, like, ‘OK! We go back on meds and it runs its course,’” he said.
Far harder to heal was the psychological trauma — the dashed hopes at finding out he wasn’t cured after all of either the disease or the stigma that accompanies it.
Until then, he hadn’t completely realized the weight he was still carrying. The weight of the memories of those dark days in one of the epicenters of the AIDS epidemic, caring for friends dying of AIDS when support systems were scarce and some hospital orderlies refused to even deliver food to patients’ rooms. The weight of rejection and abandonment from the men who refused to date him because he was HIV positive. The weight of the illusion that HIV is a “manageable” disease when it had given him life-threatening cancer. The weight of three decades of worries.
He even felt that he had disappointed Henrich and the research team, with whom he’d developed a deep bond.
“I remember meeting with Tim and the team afterwards,” Steinkohl said, “and he essentially talked me down, saying ‘Don’t go down that path. What you and others have done has helped change the course of cure research. There is a tremendous amount we can learn from you. ’”
Henrich’s reassurances were reinforced last week at the biennial meeting of the International AIDS Society in Durban, South Africa, the largest global health conference in the world. Previous efforts to duplicate Brown’s results had been unsuccessful, largely because the patients died from either the cancer or the transplant. But last week, Dr. Annemaire Wensing of Ultrecht University in the Netherlands reported on a study of 15 patients with HIV who underwent transplants for cancer. Of the 15, six survived. Of the six, three are now a year or more post-transplant and show no or just a trace of HIV using the most sensitive tests. Only one had an HIV-resistant donor.
But while their HIV may be cured or in remission, the only test is to take them off their medication — something that has not yet been done precisely because of lessons learned from the two Boston patients. Moreover, research in preclinical models has shown that maintaining antiretroviral therapy well beyond transplantation may allow the immune system more time to recover, said Fred Hutch’s Dr. Chris Peterson, part of the Fred Hutch-based defeatHIV group.
Steinkohl now divides his time between New York City and Northwest Connecticut and looks forward to being married in the fall to a man who has known “since Day One” his HIV status and all he has been through.
He remains part of the study, though he no longer gives blood specimens regularly — something he loathed but would do again in a heartbeat if needed. In fact, despite the emotional turmoil he has endured, he said he would do it all again.
“I deeply appreciate, respect, and admire the cure research world, their dedication, and continuance,” he said. “It is such a long, slow slog. I am deeply grateful to them for continuing to keep at it. My deep disappointment is on a personal level. It is significantly outweighed by my satisfaction at helping advance research.”
The public is invited to attend the free talk "Cured/Not Cured: A Tale of Two Diagnoses" at 7 p.m. Wednesday at Fred Hutch's Pelton Auditorium. See details here. The Conference on Cell and Gene Therapy for HIV Cure takes place Thursday and Friday, with keynote speaker Dr. Larry Corey and plenary speakers Drs. Warner C. Greene, Timothy Henrich, and Mark Kay. See details here.
Mary Engel is a former staff writer at Fred Hutchinson Cancer 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.