Third Transplant Patient Cured of HIV Marks Important Firsts

This week's news that a third person has been "cured" of HIV through a unique transplant of stem cells has given hope for a larger-scale way to beat back the HIV epidemic that has plagued the world for decades.

But while this case is certainly cause for celebration, experts involved in the effort say we are still a long way from a universal cure.

Researcher Yvonne Bryson, MD, chief of pediatric infectious diseases at UCLA, told those attending a conference on infectious diseases Tuesday that this case is special. The patient was a woman living with HIV who is multiracial. The previous two patients were men: one white, one Latino.

The woman in this case was given transplants of stem cells and umbilical cord blood to treat leukemia. The treatment not only sent her cancer into remission, but her HIV as well.

The success of this case suggests that cord stem cell transplants should be considered to produce remission and cure for those with HIV who also have cancers and other diseases, the researchers say.

While the news was met with excitement in the scientific community, the approach will not be available universally, since the transplants were all done to treat cancers in the three HIV-infected patients. ''There are approximately 50 people per year who may benefit from this," Bryson estimates.

Even so, other experts say the approach could provide insight into other ways to find cures. And Bryson says it opens up options for more diverse populations.

Sharon Lewin, MD, president-elect of the International AIDS Society, called the report exciting and put the findings in perspective.

"A bone marrow transplant is not a viable large-scale strategy for curing HIV, but it does present a proof of concept that HIV can be cured," she says. "It also further strengthens using gene therapy as a viable strategy for an HIV cure."

The woman needed a stem cell transplant after being diagnosed with leukemia, a blood cancer. The stem cell transplant technique used was also novel, Bryson says. The medical team used a combination of adult stem cells from a relative's blood and umbilical cord blood from a cord-blood bank that had a rare mutation that makes the immune system resistant to HIV.

In the previous two cases of HIV cures after transplants, both patients were treated with stem cell transplants, with the same mutation, but from bone marrow transplants, a more difficult procedure. And no cord blood was used for those.

The combination of adult cells and cord-blood cells proved to be the ticket to success. Using the adult cells provides a kind of bridge that helps until the cord blood takes over, the researchers say. By day 100 after the transplant, Bryson says, the woman basically had a new immune system.

HIV remained undetectable in T cells and in bone marrow. And 37 months after the transplant, the woman stopped taking the anti-retroviral treatment commonly given to treat HIV infection.

''She is currently clinically well," Bryson says. Her cancer is also in remission.

Case Histories: Three Patients

The woman, who is middle-aged, has requested privacy, asking that neither her age nor other details be released. But the researchers did provide some background on her medical history and her route back to health. She was diagnosed with HIV in 2013 and began treatment with antiretroviral therapy (ART). Four years after her HIV diagnosis, she developed high-risk acute myelogenous leukemia, a blood cancer. The transplant was done to treat that.

Her recovery was much less bumpy than that of the previous two patients, the researchers say. She left the hospital 17 days after the transplant. She didn't have serious complications like the first two, who developed a condition that occurs when donor bone marrow or stem cells attack the recipient.

"This case also suggests that it's the transplant of HIV-resistant cells that was key to achieving a cure here," says Lewin, from the International AIDS Society. The first patient who had HIV remission after a stem cell transplant, a white man, stayed in remission for 12 years and was termed cured. But he died of leukemia in September 2020. The other, a Latino man, has been in remission for more than 30 months.

HIV Statistics, Ethnic/Racial Burdens

In the U.S., about 1.2 million people have HIV, according to HIV.gov, although 13% don't know they have it. In 2019, 34,800 new infections were diagnosed.

Certain ethnic and racial groups are more affected by HIV than others, given their proportions in the U.S. population, federal statistics suggest. In 2019, for instance, African Americans were 13% of the U.S. population but 40% of those with HIV. Hispanics/Latinos represented 18.5% of the total population but 25% of those diagnosed with HIV.

Disparities also affect women unequally, with Black women disproportionally affected, compared to women of other ethnic and racial groups. Annual HIV infections remained stable overall among Black women from 2015 to 2019, but the rate of new HIV infections among Black women is 11 times that of white women and 4 times that of Latinas, according to federal statistics.

Expert Perspective, Reactions

Vincent Marconi, MD, a professor of infectious diseases at Emory University School of Medicine, whose research focuses on disparities in HIV treatment responses, called the news "an exciting development for the cure agenda. This is the first woman to have been cured for at least 14 months, and they used cord blood, which could allow for potentially less toxic regimens and fewer adverse effects."

Although the approach, meant to be used to treat the cancers, will not be widely available, he says that ''it does provide insight into somewhat related alternative models of cure involving gene therapy."

Meanwhile, Marconi and other researchers are also focusing on the concept of long-term HIV remission if a cure is not possible. Among the strategies under study are gene editing and immune-based treatments. HIV remission is generally defined as having an HIV viral load that is not detectable after stopping treatment.

Sources:

Conference on Retroviruses and Opportunistic Infections (CROI), Feb. 15, 2022.

Yvonne Bryson, MD, chief of pediatric infectious diseases, UCLA David Geffen School of Medicine.

Vincent Marconi, MD, professor of infectious diseases, Emory University School of Medicine, Atlanta.

HIV.gov: "What is the Impact of HIV on Racial and Ethnic Minorities in the U.S.?" "U.S. Statistics."

Current Opinion in HIV and AIDS: "Progress in achieving long-term HIV remission."

National Institutes of Health: "Researchers document third known case of HIV remission involving stem cell transplant."

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