In 2017, a middle-aged woman with leukemia and an HIV infection received a transplant of HIV-resistant stem cells. Since then the mixed-race woman, known as the “New York patient”, has tested negative for HIV. She is the fourth patient that has ever been cured of HIV.  The “Berlin patient” was the first person to be cured of HIV in 2009, and since then, two other men—the “London patient” and “Düsseldorf patient”—have also been rid of the virus.

HIV is a lifelong infection and the virus typically cannot be fully eradicated. If left unchecked, the infection precipitates into AIDS, a disease that damages the immune system and makes it almost impossible for the body to fight other diseases, and shortly after the patient dies. Thankfully, daily antiretroviral therapy can reduce the amount of HIV in the blood to levels that are undetectable with standard tests, keeping the virus suppressed and drastically improving patient outlook.

In 1996, the total life expectancy for a 20-year-old person with HIV was 39 years. In 2011, the total life expectancy jumped up to about 70 years thanks to new and better antiretroviral drugs. Thirty years ago, being diagnosed with HIV was considered a death sentence. Today, people with HIV can actually live long and healthy lives.

But despite these massively improved outlooks, the lives of HIV patients are still not easy. Researchers have previously found that HIV-positive people on antiretroviral therapy live just as long as their HIV-negative peers, but their quality of life is not on par – on average, they had major comorbidities 16 years earlier than HIV-negative people. Then there are major challenges like adhering to the therapy (which needs to be taken for life), side effects, and the ever-present social stigma of being HIV-positive.

This is why scientists haven’t given up on finding a cure for HIV, despite the apparent success of antiretroviral therapy.

A mutation that blocks HIV

Until not too long ago, many thought such a thing was downright impossible. But then came the announcement of the Berlin patient in 2009, who received a bone marrow transplant from a donor who was naturally resistant to HIV in 2007. The virus was never detected in his body again. He was in effect “cured”.

The transfer came from a donor that had a rare mutation in part of their DNA called the CCR5 gene, which confers resistance to the deadly virus by preventing it from entering and infecting cells. Mutations to CCR5 essentially lock the door and give people resistance to HIV.

This therapy was further demonstrated with the London and Düsseldorf patients, who both also flushed HIV out of their system. However, all of the cured patients, thus far, were white.

The CCR5-delta32 mutation is present in only around 1% of white people and is even rarer in other populations. This rarity limits the potential to transplant stem cells carrying the beneficial mutation into patients of color because stem cell transplants usually require a strong match between donor and recipient.

Given the difficulty of finding a compatible adult donor with the CCR5-delta32 mutation for the New York patient, researchers at the University of California, Los Angeles (UCLA) and the Johns Hopkins University School of Medicine instead transplanted CCR5-delta32-carrying stem cells from banked umbilical cord blood to try to cure both her cancer and HIV simultaneously. Donor stem cells taken from umbilical cord blood only need to be a partial match to the recipient, which makes it a more practical option.The patient received her transplant in 2017 at Weill Cornell Medicine thanks to a team of transplant specialists led by Drs. Jingmei Hsu and Koen van Besien.

To increase the procedure’s chances of success, the umbilical cord blood cells were infused alongside stem cells from one of the patient’s relatives.

“With cord blood, you may not have as many cells, and it takes a little longer for them to populate the body after they’re infused,” says  Yvonne Bryson of UCLA, who co-led the study. “Using a mixture of stem cells from a matched relative of the patient and cells from cord blood gives the cord blood cells a kick start.”

The transplant successfully put both the patient’s HIV and leukemia into remission, and this remission has now lasted more than four years. She is now off HIV antiviral medication and doctors say she has now been HIV-negative for more than 30 months since stopping antiviral treatment.

“This study is pointing to the really important role of having CCR5-delta32/32 cells as part of stem cell transplants for HIV patients, because all of the successful cures so far have been with this mutated cell population, and studies that transplanted new stem cells without this mutation have failed to cure HIV,” says Persaud. “If you’re going to perform a transplant as a cancer treatment for someone with HIV, your priority should be to look for cells that are CCR5-delta32/32 because then you can potentially achieve remission for both their cancer and HIV.”

Not an option for everyone

Despite the resounding success of CCR5-delta32 stem cell transplants for flushing out HIV, such therapies are extremely invasive and dangerous. The treatment involved destroying the patient’s bone marrow with radiation and chemotherapy and then having a bone marrow transplant. This very risky therapy was used on the cured HIV patients because they all also suffered from leukemia and would have had to undergo bone marrow transplants anyway. The approach is also too expensive for the 38 million people, many in sub-Saharan Africa, thought to be living with an HIV infection.

Nevertheless, these amazing cases show that HIV can be cured and offer hope that a potentially less invasive therapy that is just as effective could be possible.

The new findings were reported in the journal Cell.