SEATTLE – The most important thing to know about the apparent HIV cure widely reported in the press recently is that the treatment was worse than the infection, according to John Mellors, MD, chief of the division of infectious diseases at the University of Pittsburgh.
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Dr. John Mellors
Dr. Mellors moderated a presentation at the Conference on Retroviruses and Opportunistic Infections about what the cure involved.
An HIV-positive man with advanced Hodgkin’s lymphoma had an allogeneic bone marrow transplant in 2016 after failing first-line chemotherapy and multiple salvage regimens. His donor was homozygous for a gene mutation that prevents HIV from entering new cells. The transplant took; the man’s hematopoietic system was replaced by one with the anti-HIV mutation; and there’s been no trace of active virus in his system since. He’s been off of antiretrovirals for a year and a half. The cancer hasn’t returned.
He’s been dubbed the “London patient.” He joins the “Berlin patient” as the second person who appears to have been freed of infection following a stem cell transplant with the anti-HIV mutation. The Berlin patient recently identified himself as Timothy Ray Brown; he was in the audience at CROI and was applauded for coming forward and sharing his story.
Mr. Brown received a transplant for acute myeloid leukemia and has been off antiretrovirals now for about a decade with no evidence of viral rebound.
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Dr. Ravindra Gupta
Although it didn’t get much attention at CROI, there was a poster of a similar approach seeming to work in a third patient, also with leukemia. It’s been tried – but failed – in two others: one patient died of their lymphoma and the transplant failed in the other, said lead investigator on the London patient case, Ravindra Gupta, MD, a professor in the division of infection & immunity at University College London.
Dr. Mellors pointed out that “the two people who have been cured had lethal malignancies that were unresponsive to conventional therapy and had the extreme measure of an allogeneic bone marrow transplant. Allogeneic bone marrow transplant is not a walk in the park. It has a mortality of 10%-25%, which is completely unacceptable” when “patients feel great on one pill a day” for HIV remission and pretty much have a normal life span.
The transplant reactivated both cytomegalovirus and Epstein Barr virus in the London patient, and he developed graft-versus-host colitis. He survived all three complications.
The take-home message is that “these cases are inspirational. The work ahead is to find out how to deliver the same results with less-extreme measures,” Dr. Mellors said.
The donors for both the London and Berlin patients were homozygous for a delta 32 deletion in the receptor most commonly used by HIV-1 to enter host cells, CCR5. Cells that carry the mutation don’t express the receptor, preventing infection. The mutation prevalence is about 1% among Europeans.
Of the two failed cases, the person who died of lymphoma had a strain of HIV-1 that used a different receptor – CXCR4 – so it’s doubtful the transplant would have worked even if he had survived his cancer.
The London patient wasn’t what’s called an “elite controller,” one of those rare people who suppress HIV without antiretrovirals. His viral loads bounced right back when we was taken off them prior to transplant.
He’s not interested in an active sex life at the moment, Dr. Gupta said, but he might be soon, so Dr. Gupta plans a discussion with him in the near future. Although the London patient could well be immune to HIV that uses the CCR5 receptor, he might not be immune to CXCR4 virus, and he might still be able to produce infectious CCR5 particles. Time will tell.
There was no industry funding for the work. Dr. Gupta is a consultant for ViiV Healthcare and a speaker for Gilead.
SOURCE: Gupta RK et al. CROI 2019, Abstract 29.