One evening in March 2020, a doctor walked out of a hospital in the Argentine city of Esperanza cradling a styrofoam cooler. He handed it to a young man who’d been waiting outside for hours, who nestled it securely in his car and sped off. His destination, a biomedical research institute in Buenos Aires, was 300 miles away, and he only had until midnight to reach it. If the young man didn’t make it, the contents of the cooler — more than 500 million cells from his sister’s placenta — would be lost, along with any secrets they might be holding.
The woman was a scientific curiosity. Despite being diagnosed with HIV in 2013, she’d never shown any signs of illness. And traditional tests failed to turn up evidence that the virus was alive and replicating in her body. Only the presence of antibodies suggested she’d been infected. Since 2017 researchers in Argentina and in Massachusetts had been collecting blood samples from her, meticulously scanning the DNA of more than a billion cells, searching for signs that the virus was still hiding out, dormant, ready to roar to life if the conditions were right.
They wanted to do the same with her placenta because even though it’s an organ of the fetus, it’s loaded with maternal immune cells — a target-rich environment to mine for stealth viruses.
As the scientists reported Monday in Annals of Internal Medicine, they didn’t find any. This means the woman, whom they are calling the “Esperanza Patient” to protect her privacy, appears to have eradicated the deadly virus from her body without the help of drugs or a bone marrow transplant — which would make her only the second person believed to have cured herself of HIV.
“This gives us hope that the human immune system is powerful enough to control HIV and eliminate all the functional virus,” said Dr. Xu Yu, an immunologist at the Ragon Institute of Mass General, Massachusetts Institute of Technology, and Harvard and senior author on the new report. “Time will tell, but we believe she has reached a sterilizing cure.”
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The discovery, which was previously announced at the Conference on Retroviruses and Opportunistic Infections in March, could help identify possible treatments, researchers said.
About a decade into the AIDS pandemic, doctors began to find a handful of patients who tested positive for the HIV virus but experienced no symptoms and were later found to have vanishingly low levels of the virus in their bodies. At the time, these case studies were presumed to be one-offs.
But the more doctors looked, the more such patients they discovered. The past few decades have revealed that people with unusually potent immune responses make up about 0.5 percent of the 38 million HIV-infected people on the planet. Scientists call these people “elite controllers,” and in recent years they have become the subject of intense international study.
In one patient Yu examined with Dr. Steven Deeks, a longtime HIV researcher and professor of medicine at the University of California San Francisco, the researchers didn’t find any intact virus in more than 1.5 billion of her cells. Loreen Willenberg, a 67-year-old California woman, had maintained control of the virus for nearly three decades without the use of antiretroviral drugs. If the Esperanza Patient is the second person known to have been naturally cured of HIV, Willenberg is the first.
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Their bodies could represent a model of a cure for HIV; if researchers can figure out what makes elite controllers special, they might be able to bottle it up into medicines, gene therapies, or other one-time treatments that could free millions from a lifetime of taking antiretroviral drugs. They might even find ways to boost the immune systems of non-responders — people whose natural defenses were so ravaged by HIV that they’re hyper-susceptible to a host of other health woes.
One of HIV’s dirtiest tricks is that when it enters a cell — usually a T cell or other immune cell — it makes a DNA copy of itself that integrates into that cell’s genome. So when that cell’s protein-making machinery comes across that bit of viral code, it unwittingly builds more copies of the HIV invader. Antiretroviral drugs disrupt this process, buying patients’ immune systems time to find and kill these hijacked cellular factories. But some DNA copies of the viral blueprint persist. In theory, they could wake up and start making a virus at any time.
That’s why people need to take antiretroviral drugs for life and why they can never be cured; doctors have no way of attacking or wiping out these latent integrated HIV genomes. And until recently, there weren’t even good methods for detecting them. But Yu’s group has been at the forefront of developing ways to allow scientists to crack open billions of immune cells and sort through their DNA looking for the smoking remains of infections past.
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Deeks said he’s most curious to learn more about what happened during the first few days and weeks after the Esperanza Patient was infected. For some reason, her body didn’t develop antibodies to all the various HIV proteins one might expect. That suggests her natural defenses slammed the brakes on viral replication early, before the virus could spread and overwhelm her immune system. Usually, that only happens if someone starts antiretroviral drugs very early.
It can be a little tricky to study what happened in someone’s body nearly a decade ago. Many of the immune system’s players are transient molecules, and unearthing evidence of them now may be nearly impossible — like trying to find a fossil of a jellyfish or a flatworm. But Deeks said comparing her DNA or immune cell gene expression to other patients’ might reveal something interesting.
Those are the types of analyses Yu’s group is now working on, together with the Esperanza Patient’s physician, Dr. Natalia Laufer, an HIV researcher at El Instituto de Investigaciones Biomédicas en Retrovirus y SIDA in Buenos Aires who studies elite controllers.
In an e-mail, the Esperanza Patient told STAT that she doesn’t feel special, but rather, blessed for the way the virus behaves in her body. “Just thinking that my condition might help achieve a cure for this virus makes me feel a great responsibility and commitment to make this a reality,” she wrote. Her first child is healthy and HIV-free, and she and her partner are now expecting a second, said the woman, who did not want to be named.
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Laufer calls it a “beautiful coincidence” that Esperanza translates to “hope.”
“That individuals can be cured by themselves is a change in the paradigm of HIV,” Laufer said. She added, however, they may never be able to say “cure” for sure, because it would require the impossible task of sequencing every one of the patient’s cells. But, Laufer said, “we are seeing indications that it’s possible for some individuals to completely control infection with HIV. And that’s very, very different from what we thought 40 years ago.”
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