MUNICH, Germany – “You can’t imagine what I went through,” says Marc Franke, a 55-year-old German software engineer who has achieved global fame within the scientific community after becoming just the second person ever to be cured of HIV.
More commonly known within medical circles as “The Dusseldorf Patient,” Franke had his entire immune system erased with powerful chemotherapies 11 years ago. Once that was complete, he underwent a transplant to receive new immune cells, created using stem cells taken from a donor with a genetic resistance to HIV.
The process was both drastic and debilitating. But it basically gave him a new immune system.
To avoid rejecting this new immune system, Franke had to endure four years of immunosuppressant drugs plus a cocktail of other treatments to manage the side effects he began suffering. As consequences of the powerful medications, he developed liver inflammation, contracted a herpes infection that went to his brain and suffered loss of bone density which led to a broken hip.
“It was a very rocky road,” he says. “I had so many troubles.”
But five years on, Franke was able to completely stop the antiretroviral drugs preventing HIV from replicating. Today, having undergone dozens of tests and scans, he can say with confidence that there is no trace of HIV reservoirs in his body — those are the immune cells that HIV invades in the earliest stages of infection and then uses as a dormant base, enabling the virus to reactivate at any time.
The first person to be cured of HIV was Timothy Ray Brown, an American who received a pioneering stem cell transplant back in 2007, six years before Franke. There are now seven patients who have been cured. The latest case was revealed at AIDS 2024, the 25th International AIDS Conference, in Munich last week, although this patient has requested anonymity.
This septet represents a remarkable achievement. But there are major barriers to rolling out such therapies on a wider scale.
Dr. Björn Jensen, a senior consultant at Düsseldorf University Hospital who performed the procedure on Franke, points to the considerable risks. Because stem cell transplants are so invasive, many patients die in the aftermath. In the case of Franke and the six others to have been cured, a transplant was attempted because they had also developed aggressive and life-threatening blood cancer, making it the only option to save their lives.
“It wouldn’t be ethical to use widely because of the risks,” says Jensen. “In all of these cases, it was done because there was another deadly disease and then curing HIV was the bonus.”
Finding a donor is also far from easy. HIV attacks the immune system by binding to white blood cells via a receptor called CCR5. Some people -- like Franke’s donor, a former flight attendant named Anja Prause -- have two copies of genetic mutation called Delta 5 which means a portion of the CCR5 gene is deleted. As a result, HIV is unable to infect their cells. However, this mutation has only been found in Caucasians and in just 1% of the population, making it hard to identify donors even for American and European patients. In Southern Africa, where the HIV pandemic is still most severe, no people with the Delta 5 mutation have ever been identified, making stem cell transplants impractical as donors would have to be sourced from a different continent.
Finally, and most important, in many cases, such stem cell transplants do not eliminate the virus from the body. An international collaboration called IciStem has begun collecting tissue from the dozens of HIV patients who have received such transplants. The goal is to understand more about why individuals like Franke have been cured while others were not.
“The question is why was it successful in these seven cases?” says Christian Gaebler, the doctor at Berlin’s Charité hospital who presented data on the latest patient to be cured at AIDS 2024. “Were there features in the patient which gave them a better starting point to achieve HIV remission or was there something unique about the immune responses of the donor, which created a better chance of depleting these HIV reservoirs.”
For HIV experts around the globe, the race is on to try and find an explanation, and many feel that the key clues may lie in two of the seven cases, each of which has been notably different from the others.
Two possible explanations for a cure
The most remarkable cure to date is the so-called “Geneva Patient,” an anonymous individual who received a stem cell transplant in 2019 from a donor without any Delta 32 mutation -- which had been considered a pre-requisite for a cure. Despite this, doctors reported last year that the transplant had still managed to eradicate all traces of HIV from the patient’s body.
When Gaebler described the newest case at AIDS 2024, he revealed that the transplant administered came from a donor with just a single copy of the Delta 32 mutation, not the two copies considered necessary to block the virus.
“I think what we've learned from these two patients is that the CCR5 receptor is part of the story, but it's not the whole story,” says Sharon Lewin, an infectious diseases doctor and professor of medicine at the University of Melbourne who researches HIV.
Gaebler offered two plausible explanations.
One possibility: The original chemotherapy used to eradicate the patient’s immune system may have also been poisonous to HIV.
A second theory: In both instances, the patient suffered from graft versus host disease, an intense autoimmune reaction to the implanted tissue which has long been the bane of all transplants. However, it is possible that the intensity of this reaction actively contributed to the cure by destroying all remaining pools of the virus. That’s a particularly compelling idea. “This complication of the transplantation may have helped to reduce the [viral] reservoir,” says Gaebler.
Utilizing the immune system to better recognize and attack HIV is viewed as a possible new strategy. Jensen believes that some of the stem cell transplants may have inadvertently supplied the cured patients with powerful doses of neutralizing antibodies against HIV which could offer another way of reducing the reservoirs in the body. “There’s some data in recent years showing that multiple antibodies could help do this, counteracting HIV’s ability to make the reservoir more long-lasting,” he says.
Lewin and others are also investigating whether existing drugs like cancer immunotherapies can do a similar job. Early findings seem promising.
“In test tubes, you can see that these immunotherapies rev up the HIV-fighting cells,” she says. “There were certainly more of the cells [after the drug was administered], and they looked like they functioned better.”
Both Lewin and the pharma company AbbVie are now conducting trials where HIV patients will be given such immunotherapies with the aim of suppressing their infection to the extent they can stop antiretroviral drugs.
So what might the future of HIV treatment look like? Both Jensen and Lewin predict it is likely to involve a toolbox of different drugs, possibly starting with gene editing to either cut some HIV reservoirs out of cells or replicate the Delta 32 mutation by deleting part of the CCR5 gene. This would then be followed up with a combination of cancer immunotherapies or neutralizing antibodies to cleanse the immune system of the remaining reservoirs.
“You’ve got to ensure that there’s nowhere for HIV to go,” says Lewin. “But you’ve then still got to kill off the virus that’s there.”
In the next few years, the results of trials using approaches such as immunotherapies and the gene editing technology CRISPR — which is being explored as a way of cutting chronic viral infections out of human DNA — will provide clues as to whether scientists are finally closing in on a more practical cure for HIV, which could be used around the world. Franke is hopeful that his case and the biological samples he has donated to IciStem, will provide a platform for more patients to benefit in future.
“I celebrate a second birthday each year [on the anniversary of his transplant] now,” he says. “It’s on Valentine’s Day which makes it easier to remember although I have to make sure to book a restaurant well in advance. Last year I celebrated my tenth birthday with my stem cell donor.”
David Cox is a freelance health journalist who has written for publications around the world including NPR, The New York Times, Wired and The Guardian. He has a Ph.D. in neuroscience.
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