Researchers in Massachusetts say they’ve discovered a second patient who seems to have completely defeated an HIV infection without the help of antiviral treatments or a bone marrow transplant. The case of the Esperanza patient, as the woman is now being called, suggests that more people can naturally clear the viral infection than currently assumed, according to the authors. It also offers more hope that a similar cure can be found for the vast majority of patients who are burdened with HIV their whole lives.

Members of the Ragon Institute—a medical institute focused on HIV research, with scientists from the Massachusetts General Hospital, the Massachusetts Institute of Technology, and Harvard University—have been studying a particular group of HIV patients for years now. These patients are known as “elite controllers,” and they all appear to have immune systems that can effectively keep HIV in check without antiretroviral therapy (ART), the standard course of treatment.

For most infected people, ART is needed to keep the virus from replicating en masse inside certain immune cells, which eventually destroys the immune system and causes the condition known as AIDS. While ART can sink levels of HIV so low that the person is no longer contagious to others, the virus is still able to hide inside some cells and avoid complete eradication. Usually, if a person stops taking ART (or if the virus evolves enough resistance to the drugs), the virus can emerge from this reservoir and wreak havoc again. Elite controllers, on the other hand, seem to not need treatment at all, keeping their HIV viral load low on their own.

In August 2020, the group published their latest research on elite controllers. One of these patients had not only controlled the infection by herself, they argued, but had eradicated it entirely. The group was unable to find any traces of the virus in more than 1 billion blood cells taken from this patient, even using the latest genetic tests.

There have been other patients documented to have completely or practically beaten HIV. These patients are traditionally given a nickname to preserve their anonymity, usually corresponding to their locale, such as the Berlin patient. Two patients are known to have remained wholly HIV-free—what’s known as a sterilizing cure—after undergoing a bone marrow transplant. Bone marrow transplants effectively replace a person’s immune system with that of a donor’s, and both patients were given bone marrow from individuals with a rare genetic mutation thought to make them much less vulnerable to HIV infection. Though successful, bone marrow transplants are far too dangerous and cumbersome to ever become a mainstay HIV cure. There have also been other cases of people who have had persistently low levels of HIV after they stopped taking ART.

But the group’s San Francisco patient is unique even among these cases, since she never underwent any treatment. At the time, the researchers speculated that this patient may not be the only one to be found among their elite controllers. And they were seemingly right. In a new study published Monday in the Annals of Internal Medicine, they now claim to have documented a second such patient, who they’ve dubbed the Esperanza patient. As before, the group was unable to find any amount of the virus in over 2 billion blood and tissue cells collected from the woman.

“The examples of these two cases really suggest that our current efforts to find a cure for HIV infection are not elusive. If we learn how natural immunity to the virus works, we’re going to be able to do this,” study author Xu Yu, a Ragon Institute researcher, told Gizmodo by phone.

There are still many puzzles to be solved about these cases. The San Francisco patient first contracted HIV in 1992 and has long been studied as an elite controller, but it’s not known when her infection went from being contained to being conquered. The Esperanza patient, on the other hand, had lived with HIV for about seven years before Yu’s group declared her cured, which raises the possibility that a natural victory over the virus may not take so many years for those blessed with the ability to do so. The group believes that more naturally cured people are out there, unaware of their good fortune.

Of course, the most pivotal question is how the immune system of these two individuals has pulled off this trick. Yu’s group and others suspect that certain immune cells programmed to kill other immune cells hijacked by germs like HIV play a key role, but it’s likely that more than one mechanism is involved. Some of the group’s elite controllers also appear to be functionally cured, with the virus contained to parts of a cell’s genome where it can never replicate itself back to full strength.

One priority for Yu’s group is to find more of these elite controllers and naturally cured people to better understand their biology. But many researchers, including Yu and her colleagues, are already working on strategies to help other people based on what we’ve learned from those with built-in hardiness to the virus. These include therapeutic vaccines that can hopefully train the immune system to recognize reservoirs of HIV.

“The next step is going to be: How do we use therapeutic vaccines and other approaches to mimic the responses we’re seeing in these individuals over to the broader patient population?” Yu said. “If we can mimic what we’re seeing from elite controllers, not even necessarily these two patients, we can bring people at least to a kind of functional cure before we’re talking about a sterilizing cure.”