California man appears to be another person cured of HIV after a stem cell transplant

A man in southern California, dubbed the ‘City of Hope patient’, appears to be the latest person cured of HIV after receiving a stem cell transplant from a donor with a rare mutation, bringing the total to five, according to a presentation on Monday at the 24th International AIDS Conference (AIDS 2022) in Montreal.

The man remains free of HIV more than 17 months after stopping antiretroviral therapy (ART) and his leukaemia also remains in remission.

The man is older than the handful of other people previously cured after such a procedure, he has been living with HIV longer and he received a less harsh conditioning regimen prior to the transplant.

This suggests that this approach may be possible for a wider subset of HIV-positive people with advanced cancer, but it is far from feasible for the vast majority of people living with HIV.

Yet the case could provide clues that help researchers develop more widely applicable approaches for long-term HIV remission.

“The City of Hope patient’s case, if the right donor can be identified, may open up the opportunity for more older patients living with HIV and blood cancers to receive a stem cell transplant and go into remission for both diseases,” said Dr Jana Dickter of the City of Hope cancer centre near Los Angeles, who described the case at the conference and at an advance media briefing last week.

The City of Hope patient

The latest case involves a 66-year-old white man who was diagnosed with HIV in 1988. At one point, his CD4 count fell so low (below 100) that he was diagnosed with AIDS.

He started ART when it became available in the mid-1990s. In 2018, he was diagnosed with acute myelogenous leukaemia.

Complete cure or long-term remission?

Researchers are still working to learn why these cures after stem cell transplantation were successful while other attempts have failed. Using stem cells with a double CCR5-delta-32 mutation seems to be key.

At CROI 2012, researchers described two HIV-positive men in Boston who received stem cell transplants for cancer treatment from donors without the mutation. Both experienced viral rebound after stopping ART, though this was delayed.

Some have posited that the graft-versus-host reaction might play a role in eradicating HIV, but the five patients who were cured received different pre-transplant conditioning regimens and some experienced mild or no graft-versus-host disease.

Even as each new case provides more answers, stem cell transplants remain far too risky for people who do not need them to treat life-threatening cancer.

Seeing the host as ‘foreign’, the donor immune cells can attack the recipient’s tissues and organs, which may necessitate immunosuppressive therapy.

While waiting for donor cells to engraft, patients are highly susceptible to infections. What’s more, the procedure is medically intensive and costly and would be impossible to scale up to treat the millions of people living with HIV worldwide.

Nonetheless, each case offers clues that could help researchers develop strategies that lead to more widely applicable functional cures, or long-term remission without ART. Deeks, for example, hopes emerging gene-editing technologies might be used to delete or disable CCR5 receptors and make an individual’s own immune cells resistant to HIV entry.

“These cases are still interesting, still inspiring and illuminate the search for a cure,” International AIDS Society president-elect Dr Sharon Lewin of the Peter Doherty Institute for Infection and Immunity in Melbourne told reporters during an AIDS 2022 advance media briefing.

But some advocates question why these rare cures, which won’t help most people living with HIV, get so much more attention than natural or post-treatment controllers, one of whom was also described at the conference.

“I think they’re selling us a bill of goods,” DARE-CAB member Michael Louella said during the discussion following the presentation.

“I’m never going to get that [a stem cell transplant], but this other type of remission that doesn’t get so much attention could be applicable for more people.”

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