Over the past 20 years, a handful of people have been cured of human immunodeficiency virus (HIV), the virus that causes AIDS, through intensive medical procedures.
Several other people have received the treatment and also appear to be HIV-negative, but it is too early to definitively declare these patients cured. For now, they are described as being in long-term remission and their cases are considered “possible” cures. All of these patients received stem cell transplants, with cells taken either from adult bone marrow or from umbilical cord blood.
Scientists reported the first definitive cure for HIV in 2008, and since then two more definitive cures and two possible cures have been reported. The most recent reports of such cases — a definitive remedy (opens in a new tab) And a possible remedy (opens in a new tab) – was released in early 2023.
Experts say these treatments could become more common in the coming years as scientists better understand them. However, for now, these treatments are risky and largely inaccessible to the tens of millions of people living with HIV around the world. Fortunately, HIV medications, called antiretroviral therapies (ART), can significantly extend the life of HIV-positive people and reduce their risk of spreading the virus, but the medications must be taken daily and for life, can interact with other medications (opens in a new tab) and wear a low risk of serious side effects (opens in a new tab).
Scientists therefore hope that these exceptional cases of recovery will pave the way for new, more accessible treatment strategies that will rid more people of the virus.
Here’s what we know about curing HIV.
What treatments can cure HIV?
All people cured and potentially cured of HIV have been treated with stem cell transplants. In addition to being HIV-positive, all of the patients had some form of cancer, specifically acute myeloid leukemia or Hodgkin’s lymphoma. These cancers affect white blood cells, a key part of the immune system, and can be treated with stem cell transplants.
To treat these patients’ cancers and HIV simultaneously, their doctors sought stem cells from people with two copies of a rare genetic mutation: CCR5 delta 32. This mutation disables a protein on the surface of cells called CCR5, which many strains of HIV use it to break into cells. The virus does this by first attaching to a different cell surface protein and changing shape; then, it takes over CCR5 to invade the cell. Without CCR5, it’s essentially locked.
(Some less common strains of HIV use a different surface protein, called CXCR4, instead of CCR5, and some strains can use both, according to a 2021 review in the journal Frontiers in immunology (opens in a new tab). Therefore, before their transplants, patients were screened to ensure that most or all of the virus in their body was using CCR5.)
To prepare for the transplant, patients underwent aggressive radiation or chemotherapy to eliminate cancerous and HIV-vulnerable T cells – a type of immune cell – in their bodies. This weakened the patient’s immune system until the transplanted stem cells could produce new HIV-resistant immune cells. For some time after the transplant, patients also took immunosuppressive drugs to prevent graft-versus-host disease (GVHD), where donor-derived immune cells attack the body.
Most patients received stem cells taken from the bone marrow of adult donors. These cells must be carefully “matched,” which means the donor and recipient must carry specific proteins, called HLAs, into their body tissues. An HLA mismatch can lead to a catastrophic immune reaction.
A patient — the first woman to undergo a stem cell transplant for HIV and go into long-term remission – received stem cells from umbilical cord blood that had been donated when a baby was delivered. These immature cells adapt more easily to a recipient’s body, so the patient must have been only “partially adapted”. She also received stem cells from an adult relative, to help boost her immune system when the umbilical cells took over.
Since umbilical cord stem cells do not need to be perfectly matched and are easier to obtain than bone marrow, such transplants could potentially be offered to more patients in the future.
However, HIV-positive patients should not undergo the risky procedure unless they have another disease requiring stem cell transplantation, Dr. Yvonne Bryson (opens in a new tab)director of the Los Angeles-Brazil AIDS Consortium at the University of California, Los Angeles and one of the recovered patient’s physicians, said at a press conference in March 2023.
Who was the first person cured of HIV?
The first person to be cured of HIV was initially called the “Berlin patient” because he had been treated in Berlin, Germany. In 2010, he revealed his identity.
American Timothy Ray Brown was diagnosed HIV-positive in 1995 while attending university in Berlin (opens in a new tab) and started ART to reduce the amount of HIV in his body. In 2006, Brown was diagnosed with acute myeloid leukemia, and in 2007 he received radiation therapy and a bone marrow transplant to treat the disease. Brown’s doctor saw this as an opportunity to treat his patient’s leukemia and HIV at the same time.
Brown was HIV-negative after radiation therapy and the transplant, but his cancer later returned and he needed a second transplant in 2008. That year, researchers announced that the The ‘Berlin patient’ was the first person to be cured of HIV (opens in a new tab).
Brown remained HIV free until the end of his life. He died of cancer in 2020 at 54, after his leukemia returned and spread to his spine and brain.
How many people have been cured of HIV?
As of March 2023, three people have been cured of HIV and two others are in long-term remission.
In addition to Timothy Ray Brown, those healed include the london patient, later revealed to be Adam Castillejo; and the anonymous patient from Düsseldorf. The two possible cures for HIV include a man known as City of Hope Patient and the New York patient, the first woman to receive the treatment.
Currently, there is no official distinction between being cured and being in long-term remission from HIV, Dr Deborah Persaud (opens in a new tab)who helped oversee the New York case and is the acting director of pediatric infectious diseases at Johns Hopkins, said at a press conference in March 2023.
“[The Düsseldorf patient] was probably the second person to be cured, but the team was really conservative, and stopped antiretroviral therapy after several years, and waited a long time to conclude that he was cured,” Dr Steven Deeks (opens in a new tab)an HIV expert and professor of medicine at the University of California, San Francisco, who was not involved in the patient’s case, told Live Science in an email.
The Düsseldorf patient was treated in 2013, continued on antiretroviral therapy for almost six years and has been off medication for more than four years. Meanwhile, Castillejo received his transplant in 2016, stopped ART just over a year later and was confirmed cured in 2020, before the Düsseldorf patient.
What can we learn from the cures for HIV?
These cases provide insight into how the body changes after a healing transplant as well as insight into future strategies for curing HIV.
Scientists have found that even after the transplant, the supersensitive tests detect “sporadic traces” of HIV DNA and RNA (a molecular cousin of DNA needed to make proteins). However, these viral remnants cannot replicate, said Dr Björn-Erik Ole Jensen (opens in a new tab)a chief physician at the Düsseldorf University Hospital who carried out exhaustive tests on such remains of the Düsseldorf patient.
This means that none of these viral traces could copy each other, he told Live Science. Doctors involved in the other healing cases performed similar tests and got the same result.
Changes in the immune system might be a better measure of a transplant’s effectiveness, Jenson told Live Science. For about two years after the transplant, the Düsseldorf patient carried immune cells that reacted to HIV-related proteins, meaning he had encountered and stored a “memory” of the virus.
“But over time, those responses faded away,” Jenson said, as the functional HIV reservoir dwindled to zero. This change in immune activity was a convincing sign that the Düsseldorf patient could stop ART, he added.
Are scientists looking for other ways to cure HIV?
Scientists are working on alternative treatments that can trigger these same changes in the body without relying on donor stem cells, Jenson said. By avoiding stem cell transplants, future treatments could eliminate the need for harsh chemotherapy, radiation therapy, and immunosuppressants, as well as the risk of GVHD.
Some research groups are developing a cure for HIV based on a modified cancer therapy (opens in a new tab)in which they take some of a patient’s immune cells, suppress the CCR5 receptor and make the cells reactive to HIV proteins before returning them to the body.
Another potential healing strategy involves gene therapies that modify the DNA of cells in the body, to delete the CCR5 gene. (opens in a new tab) or to induce cells to make proteins that block or deactivate CCR5 (opens in a new tab). Some researchers are developing ways to target CXCR4 (opens in a new tab).
“With the gene-editing revolution happening in other areas of medicine right now, we may one day be able to do it all at once,” Deeks said. These approaches are still being tested in lab dishes and animals, so scientists don’t yet know how they would work in humans, Jenson noted.
Nevertheless, “I think there is hope.”