HIV-1 Infection Cured in Older Patient After Reduced-Intensity HSCT for AML

By Patrick Daly - Last Updated: May 21, 2024

An older patient with acute myeloid leukemia (AML) who received reduced-intensity conditioning hematopoietic stem cell transplantation (HSCT) appeared to be cured of HIV-1 infection, according to a case report presented in The New England Journal of Medicine.

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“At the time of this follow-up, the patient had been free of HIV-1 infection for 35 months after the discontinuation of antiretroviral therapy,” reported lead author, Jana Dickter, MD, an Associate Clinical Professor in the Department of Medical Specialists in the Division of Infectious Disease at the City of Hope in Duarte, California.

The patient, a 63-year-old male, was diagnosed with HIV-1 infection 31 years before undergoing transplantation. He had a history of undetectable HIV-1 RNA levels while on antiretroviral therapy and had wild-type homozygous CCR5 receptors and predominantly R5 virus.

HSCT was recommended after he experienced AML remission on salvage chemotherapy.

The patient received reduced-intensity conditioning without T-cell depletion because of his age, “unlike other HCT recipients who have had prolonged HIV-1 control,” the authors of the report stated.

The conditioning regimen included fludarabine and melphalan plus sirolimus and tacrolimus as prophylaxis for graft-versus-host disease.

The transplant donor was matched for human leukocyte antigens and had different genotypes of killer-cell immunoglobulinlike receptors compared with the patient. Notably, the donor had a Δ32 mutation that causes a CCR5-Δ32/Δ32 deletion that has been associated with resistance to HIV-1 infection, according to Dr. Dickter.

After undergoing HSCT, the patient was negative for AML and his blood, bone marrow, and reservoir sites were reported to have full chimerism with CCR5-Δ32/Δ32 donor cells. Immunity to hepatitis B virus was also achieved after the patient received vaccination.

Is HSCT a Cure for HIV?

Prior to transplant, the patient had HIV DNA present in peripheral blood mononuclear cells; after HSCT, HIV DNA was “mostly undetectable” in both peripheral blood mononuclear cells and gut tissues. Antiretroviral therapy was interrupted at 25 months post-HSCT to evaluate remission of HIV-1 infection.

At six months after interruption of antiretroviral therapy post-transplant, the patient’s cells were resistant to in vitro infection by HIV-1 CCR5 strains but not by CXCR4 or dual-tropic virus strains. The study’s authors contrasted this outcome with detectable levels of p24 antigens in CD8-depleted peripheral blood mononuclear cell samples from two healthy controls.

Further, at 12 months after antiretroviral interruption, the patient had T-cell activation in response to a CD3/CD28 beads and cytomegalovirus (CMV) peptide mix but no response to a HIV peptide mix, “which indicated the patient’s T-cell exposure to CMV but not to HIV,” the researchers stated.

Testing for intact proviral DNA showed a greater than two-log reduction in total proviruses after HSCT and no detectable intact or total proviruses after treatment interruption. The study noted that, since the time of treatment interruption, both HIV-1 RNA and cellular DNA or RNA have been undetectable, and CD4 counts ranged from 356 to 1271 cells per microliter.

“At the time of this report, the patient remains in remission from HIV and AML while receiving topical treatment for oral GVHD,” Dr. Dickter and colleagues concluded. “This case has shown that older patients who are undergoing reduced-intensity conditioning HCT for the treatment of cancer may be cured of HIV-1 infection.”

Reference

Dickter JK, Aribi A, Cardoso AA, et al. HIV-1 remission after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2024;390(7):669-671. doi:10.1056/NEJMc2312556

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