A woman who was infected with HIV in 1992 could be the first person cured of the virus without a risky bone marrow transplant or even medication, researchers reported Wednesday.
In another 63 people in their study who controlled the infection without drugs, HIV was apparently sequestered in the body in such a way that it could not reproduce, the scientists also reported. The finding suggested that these people may have achieved “functional recovery”.
The research, published in the journal Nature, describes a new mechanism by which the body can suppress HIV, only now visible due to advances in genetics. The study also offers hope that a small number of infected people who have been on antiretroviral therapy for many years could similarly suppress the virus and stop taking the drugs, which can have adverse consequences on the body.
“This suggests that the treatment itself can cure people, which goes against all dogma,” said Dr Steve Deeks, an AIDS expert at the University of California, San Francisco and author of the new study.
The woman is Loreen Willenberg, 66, of California, already famous among researchers because her body suppressed the virus for decades after a verified infection. Only two other people – Timothy Brown of Palm Springs, California, and Adam Castillejo of London – have been declared cured of HIV. Both men underwent grueling bone marrow transplants for cancer that left them with immune systems resistant to the virus.
Bone marrow transplants are too risky to be an option for most people with HIV, but the cures have raised hope that a cure is possible. In May, Brazilian researchers reported that a combination of HIV treatments could have led to another cure, but other experts said more tests were needed to confirm this finding.
“I think this is a novel, significant finding,” said Dr Sharon Lewin, director of the Peter Doherty Institute for Infection and Immunity in Melbourne, of the new study. “The real challenge, of course, is how you can step in to make this relevant to the 37 million people living with HIV”
Even among viruses, HIV is particularly cunning and difficult to eradicate. It inserts itself into the human genome and tricks the cellular machinery into making copies of it. HIV naturally prefers to hide in genes, the cell’s most active copying targets.
In some people, the immune system over time tracks down the cells in which the virus has occupied the genome. But careful examination of participants in this study showed that viral genes can be dropped in certain “stuck and locked” regions of the genome, where reproduction cannot take place, said Dr. Xu Yu, lead author of the study and researcher at the Ragon Institute. In Boston.
The research participants were so-called elite controllers, the 1% of people living with HIV who can control the virus without antiretroviral drugs.
It’s possible that some people who take antiretroviral therapy for years may also achieve the same result, particularly if they receive treatments that may boost the immune system, the researchers speculated.
“This unique group of individuals has provided me with a kind of proof of concept that it is possible with the host immune response to achieve what is truly, clinically, a cure,” Dr. Deeks said.
Elite Controllers have been studied extensively for clues on how to control HIV. Ms. Willenberg has been enrolled in such studies for over 15 years. With the exception of a test done years ago that indicated a small amount of virus, researchers have never been able to identify HIV in its tissues.
In the new study, Dr Yu and his colleagues analyzed 1.5 billion of Ms Willenberg’s blood cells and found no trace of the virus, even using sophisticated new techniques that can locate the virus in the genome.
Millions of cells in the gut, rectum and bowel also showed no signs of the virus.
“It could be added to the list of what I think is a cure, by a very different route,” Dr. Lewin said.
Other researchers were more circumspect. “It’s certainly encouraging, but speculative,” said Dr Una O’Doherty, a virologist at the University of Pennsylvania. “I need to see more before I say, ‘Oh, she’s healed. “”
But Dr O’Doherty, an expert in analyzing large volumes of cells, said she was impressed with the overall results.
Eleven other people in the study, whom the researchers called exceptional controllers, only have the virus in a part of the genome so dense and distant that the cellular machinery cannot replicate it.
Some people who suppress the virus without drugs do not have detectable antibodies or immune cells that respond quickly to HIV. But their immune systems carry a powerful memory of the virus, the team found.
Powerful T cells, constituents of the immune system, cleared cells in which viral genes had lodged in more accessible parts of the genome. The infected cells that remained contained the virus only in distant regions of the genome where it could not be copied.
“That’s really the only explanation for the findings that we have,” said Dr. Bruce Walker, a researcher at the Ragon Institute who has studied elite controllers for 30 years.
About 10% of people who take antiretroviral treatments, especially those who start taking them soon after being infected, also manage to suppress the virus even after they stop taking the drugs. Perhaps something similar is also at work in these people, experts have suggested.
HIV cure studies have focused on eradicating all hidden viruses in the genome. The new study offers a more accessible solution: if the virus only remains in parts of the genome where it cannot be reproduced, the patient can still achieve a functional cure.
“The part that’s in the ‘deserts’ gene just doesn’t matter,” Dr. Walker said. “This suggests that while we’re doing these studies, we not only need to look at the quantity of the reservoir, but we really need to look at the quality.”
Since the researchers completed the study, they have analyzed samples from 40 elite controllers and found a few more that could be considered cures, Dr. Yu said: “We believe there are definitely a lot there.”
With the help of Dr. Deeks, they contact people living with HIV who have taken antiretroviral drugs for 20 years or more and who may have successfully banished the virus to the deserts of their genomes.
Antiretroviral drugs can have serious side effects, including heart disease and organ damage, especially when taken for many years. A functional cure, if confirmed by further research, would be life-changing for patients, Dr. Yu said: “They can stop their treatment and just be cured, to be healthy for the rest of their lives.”