Wednesday, March 27, 2019
Wisdom Wednesday: The 'London Patient' New HIV Remission Raises Hope
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 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 Hodgins’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.
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."
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.
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."
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.
Scientists are down playing the significance of this case. I agree, radiation therapy followed by stem cell transplant by donors with two specific gene mutations is not a viable treatment for HIV. However, it does open the door to further research on gene mutation therapy for HIV and a host of other diseases.
I have posted previous blogs on the monumental task of mapping the human genome. Please enter ‘human genome’ into the search box on the upper left-hand corner of my blog site to review these posts.
In my practice, I whenever a patient tests for folic acid, vitamin D, vitamin B6 or vitamin B12, I assume they have a genetic defect for the conversion of that particular vitamin and recommend the bioavailable form. So I don’t recommend cyanocobalamin but either methylcobalamin or adenocobalamin. That way I error on the side of caution. However, if the patient has had the 23andme analysis, I can download the genetic codes to see just what genetic mutations are present and treat accordingly.
Genetic treatment is in its’ infancy but promises to hold the key to curing many diseases, including HIV. Stem cell therapy is, I believe, much more advanced that we have been led to believe.
Source: March 05, 2019 NIH