A 68-year-old man with HIV-1 who underwent hematopoietic cell transplant (HCT) for acute myelogenous leukemia 5 years ago has been free of HIV infection for 35 months after stopping antiretroviral treatment (ART), according to a case report.

The patient received an HCT from a donor with the rare delta-32 mutation, which causes a CCR5 deletion (CCR5-32/32) and has been associated with resistance to HIV-1 infection, Jana Dickter, MD, of City of Hope National Medical Center in Duarte, California, and colleagues wrote in the New England Journal of Medicine.

"He was the oldest person to successfully undergo a stem cell transplant with HIV and leukemia and then achieve remission from both conditions," Dickter told MedPage Today. "He also had been living with HIV the longest of any of the patients to date -- for more than 31 years -- prior to transplant."

"His case opens up the possibilities for other older persons living with HIV and a blood cancer to receive a transplant and achieve remission for both diseases if a donor with this rare genetic mutation [delta-32] can be identified," she noted.

The patient, known as the City of Hope patient, is unique among a handful of other patients who achieved HIV remission after stem cell transplants for hematologic cancers, not only because he was older and more frail, but because he also received reduced-intensity conditioning before transplant, Dickter said. Other HCT recipients who achieved prolonged HIV remission had undergone intensive immunotherapy with T-cell depletion prior to transplant.

Prior to HCT, the City of Hope patient had been on ART since 1997 and had no detectable HIV-1 RNA at the time of transplant, the authors reported. ART was halted 35 months after HCT, per current recommendations. Since then, his CD4 counts have ranged from 356 to 1,271 cells per microliter, and HIV-1 RNA and cellular DNA and RNA have remained undetectable, the authors wrote. HIV DNA in peripheral blood mononuclear cells was "mostly undetectable" in those cells and also in gut tissue after HCT. Researchers also tested for intact proviral DNA after HCT and found a more than 2-log reduction in total proviruses. No intact or total proviruses were detected after ART interruption.

His blood, bone marrow, and reservoir sites converted to full chimerism with the CCR5-32/32 donor cells, the authors concluded. At the time of the report, the patient remains in remission from HIV and his acute leukemia, while receiving topical treatment for oral graft-versus-host disease.

The current evidence is nevertheless not enough to support wider use of stem cell transplantation to cure HIV, cautioned Joel Blankson, MD, PhD, of Johns Hopkins Medicine in Baltimore.

"The problem is we don't know what the denominator is. We don't know how many times it's been tried," Blankson commented to MedPage Today. "But it is very encouraging that we've gone past 'N is equal to one' to the point where we now have 'N is equal to five'," referring to the five patients known to be in HIV remission after a bone marrow transplant -- the Berlin, London, Dsseldorf, New York, and City of Hope patients.

Blankson pointed to 2019 data from IciStem, a European collaborative investigating the potential for HIV cure in HIV-infected patients requiring stem cell transplantation for hematological disorders. At that time, 39 patients registered with IciStem had received transplants, but there were only two possible examples of a cure in that group.

In July 2023, researchers reported that a sixth person, the Geneva patient, had been in remission for 20 months and, remarkably, that person's donor did not have the protective delta-32 mutation.

Blankson said he sometimes encounters patients with HIV who ask about stem cell transplants to achieve HIV remission. In addition to emphasizing the lack of data, he also stresses that "we don't have a clear estimate of the mortality rate" for the procedure.

"And, it's going to be very expensive," he noted. "It's never going to be a high throughput procedure where lots of people can get this, I don't think."

Katherine Kahn is a staff writer at MedPage Today, covering the infectious diseases beat. She has been a medical writer for over 15 years.

Disclosures

Dickter reported no conflicts of interest. Co-authors reported ties to industry.

Blankson disclosed no conflicts of interest.

Primary Source

New England Journal of Medicine

Source Reference: Dickter JK, et al "HIV-1 remission after allogeneic hematopoietic-cell transplantation" N Engl J Med 2024; DOI: 10.1056/NEJMc2312556.

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