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A Patient May Be Free of HIV, Thanks to This Drug

A sixth person, dubbed the “Geneva patient,” may be free of HIV after receiving a stem cell transplant intended to treat another disease—his cancer. The man, who was diagnosed with HIV in 1990, continues to have no detectable virus in his blood 20 months after stopping medication to control the infection.

So far, five people are considered to be cured of HIV after undergoing stem cell transplants for cancer. All five received stem cells from donors with a rare mutation in a gene called CCR5. Found in a small number of people with Northern European ancestry, this genetic alteration has been shown to hamper HIV’s ability to enter cells.

But the Geneva patient’s case, announced ahead of the International AIDS Society Conference in Australia this week, differs in a key way. This patient’s donor didn’t possess this protective mutation and had normal stem cells. “All the markers of HIV infection very quickly decreased until they became undetectable by classic analysis within a few months,” said Asier Sáez-Cirión, an HIV researcher at the Institut Pasteur in Paris, who presented the results at a press briefing before the conference. “We consider that this person is in viral remission of infection.”

“We don’t know that this patient has been cured,” says Jeffrey Laurence, an HIV expert at Weill Cornell Medicine who was not involved with the research. “But if it’s true, it should open up a new line of research.”

The Geneva patient received chemotherapy for his cancer in 2018, followed by a stem cell transplant, which is used to replace blood-forming cells that have been destroyed by cancer or chemotherapy. When infused into the recipient, these donor stem cells enter the bloodstream and travel to the bone marrow, where they form healthy new blood cells.

In the five previous patients, it’s thought that donor cells with this mutation caused HIV remission by blocking the virus from making copies of itself. But very few people carry this mutation, and donor stem cells need to be matched to patients with a similar tissue type. This limits the chances of finding a donor, especially for non-white patients. For the Geneva patient, there was no donor available with the CCR5 trait.

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Stem cell transplantation remains a risky procedure due to serious complications such as graft-versus-host disease, in which the donor’s cells attack the recipient’s cells, damaging tissues and organs. Transplantation is used only to treat a life-threatening condition such as cancer—not HIV alone. HIV is now considered a chronic condition thanks to the development of antiretroviral drugs, which slow the replication of the virus and prevent the infection from progressing to AIDS.

After his stem cell transplant, the Geneva patient developed graft-versus-host disease and doctors treated him with a drug called ruxolitinib, which at the time was being investigated for this complication. Taken as a pill, ruxolitinib decreases inflammation associated with the disease by blocking two proteins, JAK1 and JAK2. The patient is still on ruxolitinib, but in November 2021, he went off antiretroviral therapy for HIV. His viral load remains undetectable.

Now researchers want to know whether ruxolitinib played a role in his recovery. Preliminary data presented at the conference by Emory University researchers bolsters the case for the drug: In a trial of 60 HIV patients on antiretrovirals, 40 of them were also given ruxolitinib for five weeks and followed for an additional seven weeks. Researchers then measured their viral reservoirs—groups of HIV-infected immune cells that lay dormant in the body. For 13 patients on ruxolitinib with high viral reservoirs at baseline, these sites decayed significantly.

“When you add this drug, it causes those reservoir cells to die faster,” says Christina Gavegnano, an assistant professor at Emory School of Medicine who oversaw the research. “It stops the virus from popping back out of them and infecting new cells.” Gavegnano has been studying JAK inhibitors as a potential treatment for HIV for over 10 years. She says these drugs also seem to block the characteristic inflammation seen in HIV patients and help to regulate a person’s immune system, which gets hijacked by the virus.

In a press briefing, Alexandra Calmy, the head of the HIV/AIDS unit at the Geneva University Hospitals who was involved with the patient’s care, speculated that the drug “may have an impact of reducing the reservoir and the absence of viral rebound.”

These viral reservoirs have posed a major hurdle in wiping out HIV, and researchers think a cure lies in eliminating them. When a person is on antiretroviral therapy, these reservoirs are undetectable by the immune system because the virus is dormant. But as soon as a person stops taking antiretrovirals, the virus reactivates.

Based on the rate of reservoir decay shown in the Emory study, the researchers estimate that ruxolitinib could clear nearly all viral reservoirs in about three years. But all it takes for a rebound is for one viral particle to remain active, replicate, and infect the body once again.

Gavegnano and her Emory colleagues didn’t know about the Geneva patient until two weeks before the conference, when the European team reached out. She says the timing of both groups’ presentations was serendipitous.

Jana Dickter, an infectious disease specialist at City of Hope Medical Center in Duarte, California, calls the Geneva patient’s remission “exciting and novel,” although it’s still possible that his viral load may rebound in the future. Dickter was a member of the team that treated Paul Edmonds, the fifth patient to achieve HIV remission. “The therapy ruxolitinib is thought to affect the immune system‘s response to HIV and the HIV reservoir, where HIV can persist in dormant cells for many years,” she says. “It still is yet to be determined from these different cases if certain therapies before or after transplantation contribute to HIV remission.”

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She says each case of HIV remission gives hope for new treatment strategies that could eventually help more people.

Laurence, the HIV specialist at Weill Cornell Medicine, is not convinced that the drug is the cause of the Geneva patient’s remission. “I don’t doubt that ruxolitinib may have some useful properties,” says Laurence, who is also senior scientific consultant for programs at amfAR, the Foundation for AIDS Research. But he thinks it’s more likely that the key ingredient in the case was actually the “graft-versus-host effect.” In other words, the newly transplanted cells cleared away old immune cells infected with HIV.

Laurence says a cure may be possible without ruxolitinib. He points to a study published this month, in which researchers cured two nonhuman primates of the monkey version of HIV using a standard stem cell transplant—one without the CCR5 mutation. Of the four monkeys that received transplants, two went into remission for HIV after they developed and were treated for graft-versus-host disease. Another two did not, because the virus managed to jump into the transplanted donor cells.

It’s too soon to say whether the Geneva patient’s treatment worked. Doctors will have to monitor him closely in the coming months and years to know for sure. In 2012, things looked optimistic for a pair of people known as the “Boston patients,” who had also received transplants from donors whose stem cells were normal—without the HIV-resistant CCR5 mutation. But for both of them, the virus rebounded several months after they stopped antiretroviral treatment.

But if the Geneva patient continues to be clear of the virus, it raises the possibility that the CCR5 trait may not be needed for a cure. And if Gavegnano’s modeling is correct, ruxolitinib may even offer a chance at clearing the virus in people who don’t undergo stem cell transplants. Her group will continue to study the drug in HIV patients on antiretrovirals.

“We’re getting to a point where we’re seeing that what we believed in all along does, in fact, have potential,” says Gavegnano.

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