A woman in Argentina has become only the second documented person whose own immune system may have cured her of HIV.
Researchers have dubbed the 30-year-old mother, who was first diagnosed with HIV in 2013, the “Esperanza patient,” after the town in Argentina where she lives. In English, “esperanza” means “hope.”
“I enjoy being healthy,” the Esperanza patient, who spoke on condition of anonymity due to the stigma associated with the virus, told NBC News in Spanish over email. “I have a healthy family. I don’t have to medicate, and I live as though nothing has happened. This already is a privilege.”
This is really the miracle of the human immune system that did it.
Dr. Xu Yu, Ragon Institute
The co-authors of the study, which was published Monday in the Annals of Internal Medicine, said they believe their findings will indeed bring hope to the estimated 38 million people globally living with the virus and to the ever-expanding HIV-cure research field. The case serves as one of two proofs of concept that a so-called sterilizing cure of the virus is apparently possible through natural immunity.
“This is really the miracle of the human immune system that did it,” said Dr. Xu Yu, a viral immunologist at the Ragon Institute in Boston, who in partnership with Dr. Natalia Laufer, a physician scientist at INBIRS Institute in Buenos Aries, Argentina, led the exhaustive search for any viable HIV in the woman’s body.
“Now we have to figure out the mechanisms,” said Dr. Steven Deeks, a prominent HIV cure researcher at University of California, San Francisco, who was not involved with the study. “How does this happen? And how can we recapitulate this therapeutically in everybody?”
Scientists are pursuing the byzantine task of curing HIV on multiple fronts, including through gene therapy; “kick and kill” efforts to flush the virus from its so-called reservoir or “block and lock” methods to keep it trapped in cells; and therapeutic vaccines that would enhance the body’s immune response to the virus.
To date, researchers have successfully cured two other people therapeutically — in both cases through complex and dangerous stem cell transplants.
HIV has proved extraordinarily difficult to eradicate from the body because it will infect certain long-lived immune cells, known collectively as the viral reservoir, that can spend lengthy periods in a resting state. This keeps the viral DNA, known as provirus, that is encoded into those cells under the radar of standard antiretroviral treatment, which can only attack the virus in infected cells when they are actively churning out new copies of HIV.
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 controllers of HIV. These are among the estimated 1 in 200 people with HIV whose own immune systems are somehow able to suppress the virus’s replication to very low levels without antiretrovirals.
That study’s authors found that these individuals’ immune systems appeared to have preferentially destroyed cells that harbored HIV capable of producing viable new copies of the virus. Left over were only infected cells in which the viral genetic code was spliced into a kind of genetic dead zone — regions of the cellular DNA that were too distant from the levers that propel viral replication.
One member of that cohort, Loreen Willenberg, a now-67-year-old Californian who was diagnosed with HIV in 1992, stood out as having an immune system that had apparently vanquished the virus entirely. Even after sequencing billions of her cells, scientists could not find any intact viral sequences.
Willenberg’s case of an apparent natural cure of HIV is quite similar to the Esperanza patient’s, according to Yu. The virologist theorized that each of these women may have mounted a particularly potent killer T-cell response to the virus — an immunological full-court press that researchers could possibly one day recapitulate therapeutically.
“I’m very keen to learn more about this seemingly new phenomenon of extraordinary elite control” of HIV, said Rowena Johnston, director of research at amfAR: The Foundation for AIDS Research, of how the two women’s cases have inspired her. “There’s really a lot to know.”
After the Esperanza patient began partnering with Yu’s team in 2019, the scientists searched mightily for any viable HIV in 1.2 billion of her blood cells. They also searched 500 million placenta-tissue cells after the woman gave birth to an HIV-negative baby in March 2020.
Using highly sophisticated and sensitive genetic-sequencing techniques that have only recently become available, Yu and her team once again found no intact viral sequences in the elite controller they were studying.
“The study sets the standard for demonstrating that the Esperanza patient has no replication-competent proviral DNA within her cells,” 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, which funded the study along with the Bill & Melinda Gates Foundation. “The more of these patients we uncover and work up, the more complete our understanding of what a cured patient looks like.”
An HIV-diagnosed individual would generally be considered functionally cured of the virus if they retained viral DNA in their cells that could potentially give rise to viable new copies of the virus, but which some sustained force nevertheless kept indefinitely suppressed without antiretroviral treatment.
This scenario is also sometimes referred to as post-treatment control of HIV, or viral remission. There are a number of documented cases of people who have stopped antiretroviral treatment, in particular if they started such therapy very soon after contracting the virus, who have not seen their viral load rebound for years.
In a sterilizing cure, there would be no viable HIV anywhere in the body.
“We’re never going to be 100 percent sure there’s absolutely no intact virus, no functional virus anywhere in her body,” Yu said of the Esperanza patient. “To bring what we learn from these patients to a broader patient population is our ultimate goal.”
Also inspiring the HIV-cure research field are the cases of two men in whom researchers succeeded in prompting sterilizing cures — the American Timothy Ray Brown and London resident Adam Castillejo. The men received stem cell transplants to treat acute myeloid leukemia and Hodgkin lymphoma, respectively, from donors with a rare genetic abnormality that made their immune cells resistant to HIV.
The University of Cambridge’s Ravindra K. Gupta, who is the lead author of Castillejo’s case study, said with more than four years having passed since Castillejo’s stem cell treatment with no sign of a resurgent virus, the physician was now ready to assert for the first time that the British man was almost definitely — as opposed to probably — cured of HIV.
In 2019, Björn Jensen, of Düsseldorf University Hospital, presented the case of a third man, known as the Düsseldorf patient, whom the German physician and his colleagues attested had likely also been cured through this method. Jensen told NBC News this man has still not experienced a viral rebound three years after being taken off his antiretroviral treatment.
While these three cases have stirred considerable excitement, the treatment the men received is too toxic to attempt as a cure for HIV in anyone who is not also facing cancer treatable with a stem cell transplant. Since Brown’s case was first published in the New England Journal of Medicine in 2009, scientists have failed a number of other times to cure HIV in individuals through similar means.
Brown died in Palm Springs, California, in September 2020 after his leukemia returned. He was 54. He spent the last chapter of his life eagerly championing the field of research that his own historic case study had greatly catalyzed.
According to Mitchell Warren, executive director of the HIV nonprofit organization AVAC, public and nonprofit investment in HIV cure research hit about $335 million globally in 2020 — up from $88 million in 2012. The lion’s share comes from the NIH.
Pharmaceutical companies such as Gilead Sciences and ViiV Healthcare are also investing in the pursuit for a cure of a virus that over the past four decades has killed some 36 million people worldwide.