A woman's immune system completely cured her of HIV: this is the second case in the world

The woman's own immune system may have cured her of HIV, reports NBCNews.

Photo: Shutterstock

Researchers have not been able to find any viable HIV in the woman's body even after using highly sophisticated and sensitive tests to scan over 1 billion of her cells.

A woman in Argentina became only the second documented person whose own immune system could cure her of HIV.

Researchers have dubbed the 30-year-old woman, who was first diagnosed with HIV in 2013, "Esperanza's patient," after the city in Argentina where she lives. Translated from English "esperanza" means "hope".

“I like being healthy,” Esperanza, a patient who spoke on condition of anonymity due to the virus, said in Spanish.

“I have a healthy family. I do not need medical treatment, and I live as if nothing had happened. This is already a privilege, ”she said.

The co-authors of the study, published Nov. 15 in the Annals of Internal Medicine, said they believed the results would indeed bring hope to the approximately 38 million people around the world living with the virus.

The case serves as one of two pieces of evidence that the so-called sterilizing cure for the virus appears to be due to natural immunity.

"It's truly a miracle of the human immune system that did this," said Dr. Xu Yu, a viral immunologist at the Ragon Institute in Boston, who partnered with Dr. Natalia Laufer, a physician scientist at the INBIRS Institute in Buenos Aires, Argentina, to conduct a thorough searching for any viable HIV in the woman's body.

“Now we need to figure out the mechanisms,” said Dr. Stephen Dix, a renowned HIV treatment researcher at the University of California, San Francisco, who was not involved in the study. - How did this happen? And how can we therapeutically replicate this in every patient?”

Scientists want to find a strategy for treating HIV in several ways, including through gene therapy: attempts to "kick and kill", flush the virus from its so-called reservoir, or "block" to keep it trapped in cells; and therapeutic vaccines that can enhance the body's immune response to the virus.

To date, researchers have successfully treated two other people therapeutically—in both cases with complex and dangerous stem cell transplants.

HIV has been proven to be extremely difficult to eradicate in the body because it infects certain long-lived immune cells, collectively known as the viral reservoir, that can spend extended periods of rest.

This keeps the viral DNA known as provirus, which is encoded in these cells, under the radar of standard antiretroviral treatment, which can only attack the virus in infected cells when they are actively making new copies of HIV.

Dr. Yu was also the lead author of a paper published in Nature in August 2020 that analyzed 64 people who, like the Argentine woman, are so-called elite HIV controllers.

That's about 1 in 200 people with HIV whose own immune systems are somehow able to suppress viral replication to very low levels without antiretroviral drugs.

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The authors of this study found that the immune systems of these people appeared to be predominantly destroying the cells that contained HIV, capable of producing new viable copies of the virus.

What remained were infected cells in which the viral genetic code was embedded in a kind of genetic dead zone—regions of cellular DNA that were too far from the levers that stimulate viral replication.

One member of this group, Loreen Willenberg, a 67-year-old Californian who was diagnosed with HIV in 1992, excelled for having an immune system that appeared to have completely defeated the virus.

Even after consistently examining billions of her cells, scientists have not been able to find any remnants of the virus.

Each of these women may have a particularly potent killer T-cell response to the virus, Yu said, a comprehensive immunological defense that researchers may one day be able to replicate therapeutically.

“I'm eager to learn more about this seemingly new phenomenon of extraordinary elite control over HIV,” Rowena Johnston, director of research at amfAR: Foundation for AIDS Research, said of how the two women's cases inspired her.

Since patient Esperanza began collaborating with Yu's team in 2019, scientists have carefully searched for any viable HIV in her 1,2 billion blood cells.

They also searched 500 million placental tissue cells after a woman gave birth to an HIV-negative baby in March 2020.

Using highly sophisticated and sensitive genetic search techniques that have only recently become available, Yu and her team again found no intact viral sequences in the elite controller they were studying.

"The study sets the standard for demonstrating that Esperanza's cells do not have proviral DNA capable of replication," said Carl Dieffenbach, director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases, a division of the National Institutes of Health that funded the study along with the Bill and Melinda Gates.

“The more such patients we find and treat, the more fully we understand what a cured patient looks like,” he said.

A person diagnosed with HIV is generally considered functionally cured of the virus if they retain viral DNA in their cells, which could potentially give rise to viable new copies of the virus, but which nevertheless persist indefinitely without antiretroviral therapy.

This scenario is also sometimes referred to as post-treatment HIV control or viral remission.
There are a number of documented cases in which people have stopped antiretroviral treatment, in particular if they started antiretroviral therapy immediately after contracting the virus, and who have not seen their viral load recover for many years.

With sterilizing treatment, there would be no viable HIV in the body.

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“We can never be 100 percent sure that there is no intact virus or functional virus in her body,” Yu said of Esperanza’s patient.

“Our ultimate goal is to bring what we learn from these patients to a broader range of patients,” she said.

Also encouraging research into HIV treatment are the cases of two men in whom scientists were able to find sterilizing substances - American Timothy Ray Brown and London resident Adam Castillejo.
The men received stem cell transplants for the treatment of acute myeloid leukemia and Hodgkin's lymphoma, respectively, from donors with a rare genetic abnormality that made their immune cells resistant to HIV.

Ravindra K. Gupta of the University of Cambridge is the lead author of the Castillejo case study. More than four years have passed since Castillejo's stem cell treatment, he said, with no signs of a resurgent virus.

In 2019, Bjorn Jensen of the University Hospital Düsseldorf presented the case of a third person, known as a patient from Düsseldorf, who, according to a German doctor and his colleagues, was cured with this method.

Photo: Shutterstock

Jensen said the man still hasn't recovered from the virus three years after stopping antiretroviral treatment.

While the three cases caused a lot of excitement, the treatment the men received are too toxic to attempt to use it as a cure for HIV in those who also do not face cancer that is treatable with stem cell transplantation.

Since Brown's case was first published in the New England Journal of Medicine in 2009, scientists have failed several more times to cure HIV in humans with similar methods.
Brown died in Palm Springs, California in September 2020 after his leukemia returned. He was 54 years old.

He spent the latter part of his life actively championing a field of research that was largely stimulated by his own historical research.

Government and nonprofit investment in HIV treatment research totaled about $335 million globally in 2020, up from $88 million in 2012, according to Mitchell Warren, executive director of the HIV nonprofit AVAC.

The lion's share comes from the NIH.

Pharmaceutical companies such as Gilead Sciences and ViiV Healthcare are also investing in the development of a cure for the virus that has killed about 36 million people worldwide over the past four decades.

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