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For the first time, a woman is completely free of HIV

The virus has not been detected in the ‘New York Patient’ two and a half years after receiving stem cells from umbilical cord blood

VIH
File photo of Kayla Collins, Director of Health and Wellness at OUTMemphis, being tested for HIV.The Washington Post via Getty
Jessica Mouzo

A woman has been rid of the HIV virus for the first time after a stem cell transplant. The “New York Patient,” whose case study was published on March 16 in the Cell scientific journal, is the fourth person to successfully achieve complete remission from AIDS (the auto-immune disease caused by the HIV virus) after a transplant of stem cells with a mutation that protects cells from virus penetration. Like the other successful cases (the Berlin patient, the London patient and the Düsseldorf patient), the New York patient had blood cancer; the procedure eliminated both the cancerous tumors and the virus. Unlike the three men who received adult stem cells, she received a transplant of umbilical cord blood cells. After 30 months without a trace of the virus or use of antiretroviral medication, the study’s authors are cautiously optimistic about achieving “remission and a possible cure.”

During a video press conference, Yvonne Bryson, an infectious disease specialist with the University of California (Los Angeles) and one of the study’s authors, said, “She is currently clinically healthy. She is cancer-free and HIV-free. We’re calling it a possible cure rather than a definitive one because we want to observe her for a longer follow-up period.” Bryson indicated that, although this procedure does not apply to all people with HIV, the results are “good news” that opens the door to developing new techniques for this therapeutic strategy.

About 38 million people worldwide live with HIV, and the disease it causes – AIDS – is incurable for now. There are no preventive vaccines or drugs that can completely eliminate the virus. In most cases, it can only be controlled by administering lifelong antiretroviral treatments that reduce the viral load to a minimum. But it is never wholly eliminated because HIV often hides in a latent state in viral reservoirs. If medication is discontinued, the virus awakens and grows again.

These four reported cases of HIV remission are the exceptional result of a medical procedure that cannot be applied to everyone with HIV. The experts we consulted said stem cell transplants are a very aggressive technique with a 40% mortality rate. The procedure is intended for patients with hematological tumors that do not respond to other therapies. Because of its risks, subjecting patients to an aggressive and potentially fatal treatment is unethical when effective antiretroviral drugs can control the infection.

Two birds with one stone

The four patients underwent stem cell transplants because they had cancerous blood tumors that did not respond to therapeutic alternatives. The procedure involves emptying the patient’s bone marrow, where the blood-forming stem cells are found, to extract all the tumors. Then the marrow is repopulated with stem cells extracted from a compatible donor, killing two birds with one stone – cancer and HIV. In addition to being compatible, the donors had a specific mutation in the CCR5 gene (CCR5Δ32), which defends cells against virus penetration. When it works, the donor’s stem cells eventually replace the patient’s, reducing the patient’s hematologic tumors and providing HIV resistance.

The New York Patient is now one of several exceptional cases reported in the scientific literature over the past decade. The first success was reported in 2011: Timothy Brown, the Berlin Patient. Brown suffered from acute myeloid leukemia and underwent a transplant from a donor with the necessary CCR5 gene mutation, which rid his body of the tumor and HIV. Brown died in 2019 from leukemia but not from HIV.

Timothy Brown, the first patient to be rid of HIV; Alicante, Spain; 2019.
Timothy Brown, the first patient to be rid of HIV; Alicante, Spain; 2019.PEPE OLIVARES

Brown’s case offered new hope for defeating HIV, and the same strategy was used for Adam Castillejo, the London Patient, who had Hodgkin’s lymphoma and the HIV virus. Castillejo also underwent a transplant from a compatible donor with the CCR5Δ32 mutation – both the virus and cancer went into remission. Just a few weeks ago, the world learned that the Düsseldorf Patient, a 53-year-old man suffering from leukemia, received a stem cell transplant with the same mutation, eliminating the virus and tumor cells.

Javier Martínez-Picado is a scientist with Irsi Caixa, a Spanish HIV research organization and co-leader of the IciStem international consortium that just published the Düsseldorf Patient case. He was pleased to see the New York Patient case because it reinforces the potential for curing HIV and shows that the first Berlin Patient case was not anecdotal. “That’s four cases now,” he said, “and all are consistent in methodology and observation. This is confirmation that this intervention works and a cure is possible.”

A woman of mixed race

The New York Patient was different in several ways. She is a middle-aged woman of mixed race (self-identified) who suffered from acute myeloid leukemia four years after being diagnosed with HIV. Unlike the three men who received adult stem cells, the New York Patient received umbilical cord stem cells. In an interview with the Science Media Center, Jose Alcamí, a virologist and director of the AIDS Immunopathology Unit of the Carlos III Health Institute (ISCIII), said, “An adult stem cell marrow transplant requires a 100% match in specific genetic markers. However, transplanting umbilical cord cells only requires a 50% match, so the chances of finding a compatible donor increase exponentially. This strategy has proven effective in the [New York] patient and offers a way of identifying more donors per candidate patient.”

The patient’s mixed race complicated the search for a compatible donor with the necessary CCR5 mutation. This mutation is only present in 1% of the Caucasian population and is even less frequent in other races. Finding a compatible adult donor with this specific mutation was highly unlikely.

To increase the chances of success, HIV-resistant stem cells collected from umbilical cord blood were combined with adult stem cells from a compatible relative (albeit without the specific mutation) and transplanted in the New York Patient in 2017. Since cord blood contains fewer cells, they take longer to repopulate the body. But an infusion that included adult cells from a compatible donor helped the cord cells to adapt and grow in the body.

Martínez-Picado explains that this booster transfusion of compatible adult cells is like “sending a squad of guards to help the cord cells survive… In the other cases, we used stem or primordial cells from a compatible donor with the necessary mutation. This strategy uses a compatible umbilical cord, but since cords have fewer cells, obtaining enough to sufficiently repopulate the organism is more difficult. The adult cells are transporters that disappear in favor of the [umbilical cord] cells with the 100% match.”

The transplant was successful; 37 months after the procedure, the New York Patient stopped her antiretroviral treatments. The woman had no trace of the virus two and a half years later when the scientific study was written. “With that amount of time, it’s pretty solid stuff. I would call it a cure,” said Martínez-Picado.

No trace of the virus

No viral reservoirs capable of replication were found in the New York Patient, and the immune response activated when HIV circulates in the body has disappeared. Scientists conducting in vitro research found that the stem cells received by the New York Patient were not only resistant to the virus variants that use the CCR5 gene to penetrate cells but also prevented HIV penetration through another entry point, the CXCR4 gene. However, Martínez-Picado says since in vitro results do not always coincide with what happens in humans, a very low risk of reinfection may remain. “The message is that the infection has been cured, but I can’t say definitively that reinfection won’t happen again,” said Martínez-Picado.

Another difference with the New York Patient is that she never suffered graft-versus-host disease (GVHD), which occurs when donor bone marrow or stem cells attack the recipient.

Since the first three male patients all contracted GVHD, it’s thought that cells transplanted into the female patient attacked the few residual cells that might have remained from the recipient, ensuring the elimination of viral reservoirs. “It was assumed that patients had to first contract GVHD to go into remission. But now it seems that you need to have an undetectable amount of virus [before transplantation], as well as resistant cells [with the mutation] present in the host, naturally or through transplantation,” said Yvonne Bryson.

However, Martínez-Picado still thinks GHVD is a necessary component of the strategy. “We need to keep studying this. Graft-versus-host is a syndrome that is detected clinically. Not seeing GVHD doesn’t always mean it’s not there – it could be developing at a subclinical level where you can’t detect it.”

The study’s authors say it has “implications for racial health equity” because it broadens the opportunity for using this therapy in patients “who are of diverse ancestry and require a transplant for other diseases.”

Mayte Coiras, an ISCIII scientist and member of the AIDS Study Group of the Spanish Society of Infectious Diseases, applauds the study as “a step forward in HIV cure therapies” but cautions that they are still isolated cases, and the therapy is not valid for all people with chronic HIV infection. “Transplantation is very aggressive. There was another patient in this study who did not survive,” said Coiras. The other patient was a man who died of Hodgkin’s lymphoma after the stem cell transplant failed. Coiras also noted the difficulty of finding compatible donors with the HIV-resistant mutation.

While the experts we consulted agree it cannot be extrapolated to the entire HIV population, more studies using this procedure are underway. Other gene therapy research into a process that extracts a patient’s cells, modifies them in a lab, and then transplants them back into the patient may be more successful for treating a broader population.

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