What Researchers Have Learned About Whether it’s Possible to ‘Cure’ HIV

It’s the news that the HIV community has been waiting four long decades for: the hint that maybe, just maybe, HIV can be cured.

Principal investigator at Harvard Medical School’s Ragon Institute, Massachusetts General Hospital and Harvard Medical School and associate professor at Harvard Medical School, Dr. Xu Yu had to double-check the results. In one of her patients, test after test to detect evidence of HIV in the woman’s blood came up empty. In addition to her lab’s results, “We had complementary assays in labs in Australia, D.C. and Argentina, where the patient is from, all trying to see if they find any evidence of active virus at all, and there was absolutely nothing,” says Yu.
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All told, the international team analyzed more than 1.5 billion cells from the patient, who’s from Esperanza, Argentina, and none of the labs found intact traces of HIV’s whole genome in her samples. The woman tested positive for HIV after becoming infected from her partner, but soon after, her body’s immune system was somehow able to control the virus and prevent it from spilling more copies of itself into her body and, more importantly, block it from establishing reservoirs of latent virus in places like the lymph nodes—all without being on the powerful anti-HIV drugs that are normally needed to suppress the virus. What sets Esperanza patients apart is her ability to control the virus. Contrary to the rare few patients with the ability to manage the virus, Esperanza does not have evidence that these reservoirs exist.

“There is no way to ever say we have proof that there is not a single virus in this patient,” says Yu, who reported the latest case in the Annals of Internal Medicine. “The only thing we can say is that after analyzing a large number of cells from the patient, with the technology in our lab we cannot reject the hypothesis that the patient probably reached a sterilizing cure by natural immunity.”

If that’s indeed the case, she would be only the second case of a patient curing themselves of HIV. Yu has also written about the San Francisco patient who was the first to be diagnosed with HIV in 2020. Yu said that now researchers have another method to examine these patients so they can better understand the remarkable achievements of these individuals.

There have been previous reports of patients who stopped taking anti-HIV medications and achieved undetectable virus levels for years: Timothy Ray Brown, who’s also known as “the Berlin patient,” and most recently Adam Castillejo, “the London patient.” Both, however, had been diagnosed with cancer and benefited from having a stem cell transplant to treat it, which replaced their immune cells with ones from donors that included cells that could block HIV infection. And they likely continued to harbor latent reservoirs of HIV, which means they haven’t been entirely cured, but what scientists call functionally cured.

That doesn’t appear to be the case with the Esperanza patient. Yu and her team have analysed 1.5 billion of the woman’s blood and tissues cells since 2017. They did not discover any evidence of a viable genetic virus. The team did however find fragments containing HIV genes which suggested that the patient may have been HIV-positive at some time. Similar clues were found in the San Francisco patient.

“This person’s body did this itself,” says Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases and a long-time HIV expert on the Esperanza patient. “It just happened. That means we have got to try to measure every possible parameter and everything in that patient to see if we can find some hint that could possibly be generalized to the public.”

The patient continues to work with Yu’s team to provide blood samples for ongoing research studies. She is currently pregnant with her second child, and Yu and the patient’s doctors are discussing whether her remarkable, apparently virus-free condition means she won’t need to take anti-HIV drugs before and during delivery, as guidelines currently recommend for pregnant women who are HIV positive. She had taken these drugs for six months during her first pregnancy to ensure any virus she might have didn’t get passed on to her child during delivery. Also, the Esperanza patient will provide samples of her breastmilk to the team once the baby is born in order for scientists to determine whether it is contaminated with virus.

Although these cases have been encouraging, Yu warns that they may not apply to all HIV patients. Two of Yu’s patients belong to elite controllers. These are people who can suppress HIV in low and undetectable amounts with their immune systems, without using anti-HIV medication. Researchers don’t understand what it is about these people’s immune systems that allow them to control the virus so well, but they are studying these people intensively, looking at everything from the antibodies they make to the highway that immune cells use that includes lymphocytes.

“I continue to be cautious,” says Fauci. “You can never really tell if the virus has completely left sanctuaries in the body or are just not coming out for any number of reasons until the right set of circumstances, but this proof of concept in my mind is much more relevant than the cases of the stem cell transplant. This is because nobody altered this individual. It was just what happened. To me, a) that’s rare. And b) I don’t know for sure if she has really eliminated the virus, but even if she hasn’t, she is controlling it in a very powerful way. If we can get a handle on that, it would be helpful for us going forward in our quest to develop a cure for people affected by HIV.”

Yu feels similarly optimistic that the patients and other like-minded people who may now be coming forward will answer crucial questions. For example, whether altering anti HIV drugs might allow others to have similar responses as her patients. Yu hopes, among other things, to be able to see if the immune reactions of her patients are similar to those produced by anti-HIV medication users. It’s possible that the drug cocktails produce an immune response weaker than what’s generated by these two patients, and scientists could find ways to bolster that response. “We are actively studying the durability and strength of their responses and comparing them to people who are treated with combination therapy,” says Yu. “I’m hoping that as more people are aware of these cases, they will approach us so we can understand their immune systems better.”



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