A woman who was infected with HIV in 1992 may be the first person cured of the virus without a bone marrow transplant or medication, researchers say.
An additional 63 people in their study controlled the infection without drugs. HIV apparently was sequestered in the body in such a way that it could not reproduce.
The research, published in the journal Nature , outlines a new mechanism by which the body may suppress HIV, visible only now because of advances in genetics. The study offers hope that a small number of people who have taken antiretrovirals for many years may suppress the virus and stop taking the drugs.
“It suggests that treatment itself can cure people, which goes against all the dogma,” said Dr Steve Deeks, an Aids expert at the University of California and an author of the new study.
Suppressed virus for decades
The woman is Loreen Willenberg, 66, of California, already famous because her body has suppressed the virus for decades after verified infection.
Only two other people – Timothy Brown of California and Adam Castillejo of London – have been declared cured of HIV. Both men underwent gruelling bone marrow transplants for cancer that left them with immune systems resistant to the virus.
Bone marrow transplants are risky to be an option for most people infected with HIV, but the recoveries raised hopes that a cure was possible.
Researchers in Brazil reported in May that a combination of HIV therapies may have led to another cure, but other experts said more tests are needed to confirm the finding.
“This is a novel, an important discovery,” Dr Sharon Lewin, director of the Peter Doherty Institute for Infection and Immunity in Melbourne, Australia, said.
“The real challenge is how you can intervene to make this relevant to the 37 million people with HIV.”
Even among viruses, HIV is wily and difficult to eradicate. It inserts itself into the genome and tricks the cell’s machinery into making copies. HIV prefers to lurk in genes, the most active targets of the cell copiers.
In some people, the immune system hunts down cells in which the virus has occupied the genome. But intensive scrutiny of the participants in this study showed that viral genes may be marooned in certain “blocked and locked” regions of the genome, where reproduction cannot occur, said Dr Xu Yu, a researcher at Harvard University.
The participants were so-called elite controllers, the one per cent of people with HIV who can keep the virus in check without drugs.
It is possible some people who take antiretroviral therapy for years may arrive at the same outcome, especially if given treatment that can boost the immune system.
“This unique group provided sort of a proof of concept that it is possible with the host immune response to achieve what is clinically, a cure,” Deeks said.
Elite controllers have been exhaustively studied for clues to how to control HIV. Willenberg has been enrolled in such studies for more than 25 years. With the exception of one test that yielded a positive result years ago, researchers were not able to identify any virus in her tissues.
Yu and her colleagues analysed 1.5 billion blood cells from Willenberg and found no trace of the virus, even using sophisticated techniques.
Millions of cells from the gut, rectum and intestine turned up no signs of the virus.
“She could be added to the list of a cure, through a very different path,” Lewin said.
“It’s encouraging, but speculative,” said Dr Una O’Doherty, a virologist at the University of Pennsylvania, adding that she was impressed by the results.
Another 11 people, whom researchers referred to as exceptional controllers, have the virus only in a part of the genome so dense and remote that the cell’s machinery cannot replicate it.
Some people who suppress the virus without drugs do not have detectable antibodies or immune cells that rapidly respond to HIV. But their immune systems carry a potent memory of the virus.
Powerful T-cells, a constituent of the immune system, eliminated cells in which the viral genes had lodged in more accessible parts of the genome. The infected cells that remained held the virus only in remote regions of the genome.
“That’s the only explanation for the findings,” said Dr Bruce Walker, a researcher at Ragon Institute, Boston.
About 10 per cent of people who take antiretroviral treatment, especially those who start doing so soon after being infected, suppress the virus even after they stop taking the drugs. Perhaps something similar is at work in those people as well, experts suggested.
HIV cure studies have focused on rooting out the virus that’s hidden in the genome. The new study offers a more attainable solution: If the virus remains in only parts of the genome where it cannot be reproduced, the patient may still achieve a functional cure.
“The part that’s in the gene ‘deserts’ doesn’t matter,” Walker said.
“It suggests that as we’re doing these studies, we need to not just be looking at quantity of the reservoir, but quality.”
Since the researchers completed the study, they have analysed samples from 40 elite controllers and found a couple more that could qualify as cures, Yu said. “We believe there’s definitely many of them out there.”
With help from Deeks, they are contacting people with HIV who have taken antiretroviral drugs for 20 years or more and who may have banished the virus to the deserts of their genomes.
Antiretroviral drugs can have harsh side effects, including heart disease and organ damage, especially when taken for years. A functional cure, if it is borne out by further research, would transform patients’ lives, Yu said.
“They can stop treatment and be cured, to be healthy for the rest of their lives,” he said.
