by 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 people have received the treatment and also appear to be HIV-free, but it is too early to definitively declare these patients cured. Currently, they are described as being in long-term remission and their cases are considered “possible” cures. All these patients received stem cell transplants, with cells collected either from adult bone marrow or from umbilical cord blood.
Researchers reported the first definitive HIV cure in 2008, and since then two more definitive cures and two possible cures have been reported. The latest reports on such matters — a definitive cure (opens in a new tab) and a possible cure (opens in a new tab) – came out in early 2023.
Experts say these treatments could become more common in the coming years as researchers understand them better. But for now, these treatments are risky and largely unavailable to the tens of millions of people living with HIV worldwide. Fortunately, drugs against HIV, called antiretroviral therapies (ART), can significantly extend the life of HIV-positive people and reduce the risk of spreading the virus, but the drugs must be taken daily and for life, can interact with other drugs (opens in a new tab) and carry one little risk of serious side effects (opens in a new tab).
So the researchers hope these exceptional curtilage cases 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 the people who are cured and potentially cured of HIV have been treated with stem cell transplants. In addition to being HIV-positive, all patients had some form of cancer, specifically acute myeloid leukemia or Hodgkin’s lymphoma. These cancers affect white blood cells, a key component of the immune system, and can be treated with stem cell transplants.
To simultaneously treat these patients’ cancers and HIV, their doctors sought out stem cells from people with two copies of a rare genetic mutation: CCR5 delta 32. This mutation disables a cell-surface protein called CCR5, which many strains of HIV use to break down in cells. The virus does this by first attaching to another cell surface protein and changing shape; then it grabs hold of CCR5 to invade the cell. Without CCR5, it is essentially locked out.
(Some less common strains of HIV use a different surface protein, called CXCR4, instead of CCR5, and some strains may 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 bodies used CCR5.)
To prepare for the transplant, patients underwent aggressive radiation or chemotherapy to wipe out the cancer- and HIV-vulnerable T cells – a type of immune cell – in their bodies. This weakened the patients’ immune system until the transplanted stem cells could produce new, HIV-resistant immune cells. For some time after transplant, patients also take immunosuppressive drugs to avoid graft-versus-host disease (GVHD), in which the 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”, meaning that both the donor and the recipient must carry specific proteins, called HLA, in their body tissues. An HLA mismatch can result in 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 at the time of a baby’s birth. These immature cells adapt more easily to a recipient’s body, so the patient only had to be “partially matched”. She also received stem cells from an adult relative to help boost her immune system as the umbilical cord cells took over.
Because umbilical cord stem cells do not need to be a perfect match and they 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 that requires a stem cell transplant, 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 doctors of the cured patient, said at a press conference in March 2023.
Who was the first person to be cured of HIV?
The first person to be cured of HIV was originally called the “Berlin Patient”, because he had been treated in Berlin, Germany. In 2010, he revealed his identity.
The American Timothy Ray Brown was diagnosed with HIV in 1995 while attending a 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 the patient’s leukemia and HIV at the same time.
Brown was HIV-free after the radiation and transplant, but the cancer later returned and he needed another transplant in 2008. That year, researchers announced that “Berlin Patient” was the first person to be cured of HIV (opens in a new tab).
Brown remained free of HIV through the end of his life. He died of cancer in 2020 at age 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 a further two are in long-term remission.
In addition to Timothy Ray Brown, the curated individuals include The London Patient, later revealed to be Adam Castillejo; and the anonymous Düsseldorf patient. The two possible HIV cures 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 difference between being cured and being in long-term remission from HIV, Dr Deborah Persaud (opens in a new tab)who helped monitor the New York case and is interim director of pediatric infectious diseases at Johns Hopkins, said at a March 2023 news conference.
“[The Düsseldorf patient] was probably the second person to be cured, but the team was very conservative, stopping antiretroviral therapy after several years, waiting 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 LiveScience in an email.
The Düsseldorf patient was treated in 2013, continued ART for almost six years and has now been off medication for more than four. 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 HIV cures?
These cases provide information on how the body changes after a curative transplant, as well as insight into future strategies to cure HIV.
Researchers have found that even after transplant, super-sensitive tests pick up “sporadic traces” of HIV DNA and RNA (a molecular cousin of DNA needed to build proteins). However, these viral remnants cannot replicate, said Dr. Björn-Erik Ole Jensen (opens in a new tab)a senior physician at the University Hospital in Düsseldorf who ran exhaustive tests on such remains from the Düsseldorf patient.
That means none of these viral spores could make copies of themselves, he told LiveScience. Doctors involved in the other curtilage cases ran similar tests, and got the same result.
Changes in the immune system may be a better measure of how well a transplant has worked, Jenson told Live Science. For about two years after the transplant, the Düsseldorf patient carried immune cells that reacted to HIV-related proteins, meaning they had encountered and stored a “memory” of the virus.
“But over time, those responses disappeared,” Jenson said, as the reservoir of functional HIV dwindled to nothing. This change in immune activity was a convincing sign that the Düsseldorf patient could stop ART, he added.
Are scientists researching other ways to cure HIV?
Researchers are working on alternative treatments that can trigger the same changes in the body without relying on donor stem cells, Jenson said. By avoiding stem cell transplants, future treatments may eliminate the need for harsh chemotherapy, radiation and immunosuppressive agents, and the risk of GVHD.
Some research groups are developing an HIV cure based on one modified cancer treatment (opens in a new tab)where they take some of a patient’s immune cells, delete the CCR5 receptor and make the cells reactive to HIV proteins before returning them to the body.
Another potential treatment strategy involves gene therapies that edit the DNA of cells in the body to delete the gene for CCR5 (opens in a new tab) or to tell the cells to make proteins that block or disable CCR5 (opens in a new tab). Some researchers are developing ways to target CXCR4 (opens in a new tab).
“With the revolution in gene editing now happening in other areas of medicine, we may one day be able to do this with a single shot,” Deeks said. These approaches are still being tested in lab dishes and animals, so researchers don’t yet know how they will work in humans, Jenson noted.
Still: “I think there is hope.”
