by In 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 undergone the treatment and appear to be HIV-free, but it is still too early to declare these patients definitively 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, where cells were collected from adult bone marrow or from umbilical cord blood.
Scientists reported the first definitive cure for HIV in 2008, and two more definitive cures and two possible cures have been reported since then. The most recent reports of such cases — one definitive cure (opens in new tab) And a possible remedy (opens in new tab) – came out in early 2023.
Experts say these treatments will become more common in the coming years as scientists better understand them. For now, however, these treatments are risky and largely inaccessible to the tens of millions of people living with HIV worldwide. Fortunately, HIV medications called antiretroviral therapies (ART) can significantly extend the lifespan of HIV-positive people and reduce their risk of spreading the virus, but the medications must be taken daily and for life. interaction with other medications (opens in new tab) and wear one small risk of serious side effects (opens in new tab).
So scientists hope that these exceptional cures will pave the way for new, more accessible treatment strategies that will free more people from the virus.
Here’s what we know about curing HIV.
Which treatments can cure HIV?
All people who have been cured and possibly 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 the white blood cells, an important part of the immune system, and can be treated with stem cell transplants.
To treat these patients’ cancers and HIV at the same time, their doctors sought stem cells from people with two copies of a rare genetic mutation: CCR5 delta 32. This mutation turns off a cell-surface protein called CCR5, which many strains of HIV make. used in cells. The virus does this by first attaching itself to another protein on the cell surface and changing its shape; then it grabs CCR5 to invade the cell. Without CCR5, it’s essentially left out.
(Some less common HIV strains 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 new tab). Therefore, patients were screened prior to their transplant to ensure that most or all of the virus in their body was using CCR5.)
In preparation for the transplant, the patients underwent aggressive radiation or chemotherapy to eradicate the cancerous and HIV-vulnerable T cells — a type of immune cell — in their bodies. This weakened patients’ immune systems until the transplanted stem cells could produce new, HIV-resistant immune cells. For some time after the transplant, patients also took immune-suppressing drugs to prevent graft-versus-host disease (GVHD), in which donor-derived immune cells attack the body.
Most patients received bone marrow stem cells from adult donors. These cells must be carefully matched, meaning that both the donor and recipient must carry specific proteins called HLAs in their body tissues. An HLA mismatch can result in a catastrophic immune response.
One patient – the first woman to have a stem cell transplant for HIV and entering long-term remission – receiving stem cells from umbilical cord blood that was donated at the time of a baby’s delivery. 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 boost her immune system when the umbilical cord cells took over.
Because umbilical cord stem cells don’t have to be a perfect match and they are easier to find than bone marrow, such transplants could potentially be offered to more patients in the future.
However, HIV-positive patients should not undergo the high-risk procedure unless they have another disease that requires a stem cell transplant. Dr. Yvonne Bryson (opens in new tab)director of the Los Angeles-Brazil AIDS Consortium at the University of California, Los Angeles and one of the cured patient’s physicians, 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 initially dubbed the “Berlin patient” because he had been treated in Berlin, Germany. In 2010, he revealed his identity.
American Timothy Ray Brown was diagnosed with HIV in 1995 while attending a university in Berlin (opens in 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 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-free after the radiation and transplant, but his cancer later returned and in 2008 he required a second transplant. That year, researchers announced that the “Berlin patient” was the first person to be cured of HIV (opens in new tab).
Brown remained HIV-free until the end of his life. He passed away from 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 two more are in long-term remission.
In addition to Timothy Ray Brown, the healed include individuals the London patient, later revealed as Adam Castillejo; and the anonymous patient from Düsseldorf. The two possible HIV treatments include a man known as the City of Hope patient and the New York patient, the first woman to receive the treatment.
At present, there is no official distinction between being cured and in long-term remission of HIV. Dr. Deborah Persaud (opens in new tab)who helped oversee the New York case and is the interim 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 very conservative and stopped antiretroviral therapy after several years and waited a long time to conclude that he was cured,” Dr Steven Deeks (opens in 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 ART for nearly six years, and has now been off the medication for more than four years. Meanwhile, Castillejo received his transplant in 2016, stopped ART a little over a year later, and was confirmed cured in 2020, before the patient in Düsseldorf.
What can we learn from HIV medicines?
These cases provide information about how the body changes after a curative transplant and provide insight into future strategies to cure HIV.
Scientists have found that even after transplantation, supersensitive 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, he said Dr. Bjorn-Erik Ole Jensen (opens in new tab)a senior physician at Düsseldorf University Hospital who conducted extensive tests on such remains from the Düsseldorf patient.
That means none of these viral tracks could make copies of themselves, he told Live Science. Doctors involved in the other cures performed 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. About two years after the transplant, the Düsseldorf patient carried immune cells that responded to HIV-related proteins, meaning they had encountered and stored a “memory” of the virus.
“But over time, these responses faded,” 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 exploring other ways to cure HIV?
Scientists are working on alternative treatments that could produce the same changes in the body without relying on donor stem cells, Jenson said. By avoiding stem cell transplants, future treatments can eliminate the need for heavy chemotherapy, radiation, and immunosuppressants and the risk of GVHD.
Some research groups are developing an HIV cure based on a adapted cancer therapy (opens in new tab)in which they take away part of a patient’s immune cells, remove the CCR5 receptor and make the cells reactive to HIV proteins before they are released back into the body.
Another possible cure strategy involves gene therapies that edit the DNA of cells in the body to remove the gene for CCR5 (opens in new tab) or to prompt cells to make proteins that block or turn off CCR5 (opens in new tab). Some researchers are developing ways to target CXCR4 (opens in new tab).
“With the revolution of gene editing now happening in other areas of medicine, we may one day be able to do this with a single injection,” 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.”
