With seventh person seemingly cured of HIV, signs of hope for a broader cure

With seventh person seemingly cured of HIV, signs of hope for a broader cure

Though his real name isn’t known, there’s no doubt that he’ll go down in history. An adult man dubbed “The Next Berlin Patient” has been declared the seventh person to be cured of HIV, and his case provides valuable information that could lead to a more broadly accessible approach for the 39 million people living with the virus around the globe.

The moniker is a nod to Timothy Ray Brown, the first person cured of HIV, who was anonymously known as “The Berlin Patient” before revealing his identity.

Immunologist Christian Gaebler, M.D., M.Sc., of Charité – Berlin University Medicine, will present the new case at the 25th International AIDS conference in Munich, which runs from July 22 to 26.

In a press preview on Thursday, Gaebler described how the patient was diagnosed with HIV in 2009 and then later developed acute myeloid leukemia. In 2015, the clinical team decided the patient needed a hematopoietic stem cell transplant in his bone marrow to treat his cancer. The team “began searching for donors with this rare genetic mutation known as the homozygous delta-32 CCR5 mutation, because we know that this mutation provides natural resistance to HIV,” Gaebler explained.

CCR5 is a receptor protein on white blood cells that HIV uses to infect cells; with the delta-32 mutation, the virus can’t bind to the protein and enter the cell. As a retrovirus, HIV then inserts part of its DNA into the genomes of infected cells, forming a reservoir of viral material in the body that is tough to eradicate.

The clinicians were unable to find a donor that had two copies of the protective mutation but did manage to find someone who was heterozygous, meaning they had one copy of the gene with the mutation and one copy without it. They went ahead with the transplant and found that it not only treated the patient’s cancer but also seems to have cured his HIV.

“The patient discontinued his recommended antiviral treatment on his own in 2018 and since then, the patient is in treatment-free HIV remission,” Gaebler said. For almost six years they’ve tested his blood and other tissues and found no signs of the virus.

Because the donated cells are heterozygous for the delta-32 mutation, there is still a functional copy of the CCR5 receptor in the patient’s body that the virus could use to infect cells. In fact, the patient was originally heterozygous for the mutation, as well. Gaebler and his team hypothesize that the transplant wiped out all of the infected white blood cells and replaced them with virus-free cells. From there, the mutated receptors now prevent the virus from rebounding.

“My favorite studies are those that pose more questions than answers,” Steven Deeks, M.D., a medical researcher and clinician at the University of California, San Francisco and Zuckerberg San Francisco General Hospital, told Fierce Biotech in an email. “Theoretically, residual HIV should persist post-transplant, and there should be plenty of target cells available to support replication. This has not happened (yet).”

Of the six other known individuals cured of HIV, five of them had received donated cells from someone homozygous for the delta-32 mutation, meaning that after the transplant they had no functional CCR5 receptor for the virus to bind to. The one exception is the sixth case, “The Geneva Patient,” whose donated cells had no delta-32 mutations at all; for them, wiping out the infected white blood cells seems to have gotten rid of the virus, and it hasn’t returned even though the patient has receptors HIV could use to infect cells.

However, the Geneva patient only had 20 months of clinical follow-up when their case was reported. “A strength in our case is that we have a very, very long clinical follow-up,” Gaebler said of the Next Berlin Patient. “Every measurement that we get on top of that gives us more confidence that we’re not seeing viral reactivation.”

Heterozygosity for the delta-32 mutation is much more common than homozygosity. In Europe, it’s about 16% of the population versus 1%, Gaebler said. But bone marrow transplants are an intense procedure, and it’s not feasible to use them to treat the many millions of patients with HIV who don’t have cancer. The seven cured patients all received their transplants to treat cancers, not HIV.

But the fact that one mutated copy of the delta-32 gene may be sufficient to cure HIV is huge for the development of gene therapies. “Seeing these human cases really shows us that we maybe do not fully need to achieve a complete depletion of functional core receptors,” Gaebler said. It also reaffirms that destroying the viral reservoir—tough as that may be—can lead to long-term remission.

“We believe that this remarkable case and the results of our studies really suggest that it is possible to cure HIV even when a functional receptor for the virus is present,” Gaebler said.

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