SEATTLE — A London man has not had detectable HIV in his system for 18 months, despite not having received treatment during that period.
The remission came after the patient underwent a stem cell transplant. This makes him the second man in history — after the Berlin patient — to have achieved HIV remission after such a transplant. And that has raised questions about whether he might be cured of HIV.
“The Berlin patient was not an anomaly,” Ravindra Gupta, MD, from University College London, and his team write in their report published online today in Nature.
But it is unlikely that this will lead to widespread stem cell transplants for people infected with HIV, said Gupta, who will discuss the case this afternoon here at the Conference on Retroviruses and Opportunistic Infections 2019.
It is only “a small step in the right direction,” he told Medscape Medical News. “But with enough small steps, we can get where we need to be.”
As well as HIV, both Berlin patient Timothy Brown and the new patient — referred to as the London patient — had acute cancers that called for a stem cell transplant, a painful and invasive treatment used after other treatments have failed.
For Brown, it was leukemia. For the London patient, it was stage 4 Hodgkin’s lymphoma, a non-AIDS-related cancer more common among people with HIV.
Both patients also had stem cell donors with two genetic mutations that remove the CCR5 receptor from the surface of the CD4 T-cell. Without that receptor, most HIV strains can’t gain access to the cell and can’t spread, and — bingo — that’s the end of HIV.
The London Patient
These stem cell transplants and cancer treatments in general set up a unique environment that can be hostile to HIV.
First, the chemotherapy destroys the immune system, essentially wiping out many of the reservoirs where HIV hides, ready to replicate and reinfect the person when treatment stops. And second, new stem cells that do not express CCR5 graft on to the person’s decimated immune system.
“The donor tissue becomes your tissue,” Gupta explained.
If the chemo eliminates reservoirs, if the cancer doesn’t come back, and if the new donor tissue repopulates the immune system with HIV-resistant cells, “the chances of remission are very good.”
When Gupta’s team began their study, at the suggestion of a referring hematologist, they didn’t have much hope it would work. Not because all those factors aren’t true, but because so many things can go wrong.
“I thought either the cancer would come back or he’d rebound for another reason. You’re trying not to be too optimistic,” said Gupta. “But secretly I was fairly excited about the prospects.”
Watching and Waiting
As the transplant date neared, the team continued to test the man’s cells for reservoirs of HIV, watching as the chemotherapy laid waste to immune cells everywhere. When they found a stem cell donor, they were pleased to discover that the best match for the patient also happened to have the genetic mutation on both arms that removed the CCR5 receptors.
Through all of this, the patient stayed on antiretroviral treatment. After the transplant, though, researchers began checking the man’s CD4 and CD8 T-cells to see if they still had receptors for CCR5 on their surfaces. If they had, it would have meant that the transplant didn’t achieve its secondary goal of resisting HIV.
But they did not have the receptors. The donor’s tissue had become the patient’s tissue.
The patient, who had avoided HIV treatment for 9 years after his diagnosis, was now reluctant to discontinue treatment, despite wanting to see if the HIV had rebounded.
“I’d have to say to him, ‘I don’t know if this is going to work’ — you can’t give any reassurance,” Gupta said. “And yet there was this hope because we told him it was a possibility.”
Finally, 510 days after the transplant, the man decided to interrupt treatment. Then he Gupta’s team watched and waited for a viral rebound.
“You try to forget about it so you don’t keep counting the days,” Gupta said. “And then every so often you say, ‘Oh, it’s been another 2 months.’ That was a nice feeling to have that progression.”
But the months did pass. In the language of the study: 12 weeks, 32 weeks, 41 weeks went by without the virus rebounding. Those were all timepoints at which previous stem cell transplant recipients had seen their HIV virus levels rise. After those points, he said, “it becomes more and more a reality — this might work.”
Now, 18 months later, there is still no sign of an HIV rebound.
And this is despite the fact that the London patient underwent much less treatment than the Berlin patient. The London patient received one transplant instead of two, and did not receive post-treatment radiation.
“That’s really important because it means that the severity of treatment is less than we thought,” he said.
The findings, Gupta and colleagues write, “support the development of HIV cure strategies based on preventing the expression of CCR5.”
Unusual and Unscaleable
Although the finding is exciting, it doesn’t necessarily present a new way of curing HIV, said Anthony Fauci, MD, head of the National Institute of Allergies and Infectious Diseases at the National Institutes of Health. What we learned from Brown’s case, Fauci explained, is that a scientific hunch — manipulating CCR5 to prevent HIV from infecting cells — turned out to be true.
The London case has not expanded our insights beyond the earlier proof of concept, though, he added.
“I don’t think there’s anything new about this that we didn’t know from Tim Brown,” Fauci told Medscape Medical News.”
“If you want to then say, ‘this is how we’re going to be scaling up treatment,’ it’s not feasible,” he said. “I mean, if you happen to have a lymphoma or a leukemia and you need a Draconian procedure like a transplant anyway, then this is a good way to maybe kill two birds with one stone.”
But on its own, it doesn’t introduce any new research avenues. “It’s not broadly applicable and not scaleable under any circumstances.”
The study was funded by the Wellcome Trust. Gupta and Fauci have disclosed no relevant financial relationships.
Conference on Retroviruses and Opportunistic Infections (CROI) 2019: Abstract OA 0-02 29LB. Presented March 5, 2019.