CROI 2022: Fourth potential stem cell HIV cure – in a US woman using donor cord cells

In a session today on HIV cure research, Yvonne Bryson and colleagues from the IMPAACT research network presented important news about another potential example of an HIV cure achieved by stem cell transplantation. [1]

The case involves a woman living with HIV who was diagnosed with acute myelogenous leukemia (AML), a life-threatening cancer, in 2017. The researchers sourced cord blood stem cells from a donor homozygous for the CCR5 delta-32 mutation that prevents expression of the CCR5 co-receptor that most HIV strains use as an entryway into cells.

The aim was to treat the cancer while also generating a new immune system made up of HIV-resistant cells, following the model that has produced three other known cases of likely HIV cures in men (Timothy Ray Brown, Adam Castillejo and the Düsseldorf patient).

A difference with prior cases is that stem cells from umbilical cord blood are less efficient at generating a new immune system after transplantation, so the woman also received stem cells from the peripheral blood of an adult relative who lacked the CCR5 delta-32 mutation. Shortly after the transplant, most of the immune cells that could be detected were derived from the adult blood stem cells, but over time the proportion of cells derived from the cord blood transplant increased.

From day 100 of follow-up, all T cells and myeloid cells (monocyte/macrophages) were progeny of the cord blood transplant and therefore possessed the CCR5-delta32 mutation. As reported at the Annual Meeting of the American Society for Hematology in 2018, remission of AML was achieved and the woman initially continued on antiretroviral therapy (ART) with HIV viral load remaining suppressed. [2]

At CROI today, Yvonne Bryson reported that ART was interrupted three years after the transplant with no HIV viral load rebound. The woman, who’s described as middle aged and of mixed race, has now been off ART for more than 14 months with persistently undetectable HIV viral load (during this time they’ve received COVID-19 vaccination without any untoward effect).

Tests for HIV DNA, a surrogate measure of the HIV reservoir, have also been negative except one detection of trace amounts at an early timepoint after ART cessation. Antibody and T cell responses against HIV are no longer detectable. The absence of ART has been confirmed by measuring drug levels in blood. The researchers have tested the woman’s cells in the laboratory and found them to be resistant to HIV.

The case bolsters the evidence that an HIV cure is achievable and demonstrates that, for people with HIV and certain life-threatening cancers, stem cell transplantation from donors homozygous for the CCR5 delta-32 mutation can work in women as well as men.

Bryson pointed out that cord blood stem cell banks can be tested for the presence of the CCR5Δ32 mutation, and the approach used in this case could increase the chances of identifying CCR5-negative donors for people with HIV who require stem cell transplants for cancers (cord blood stem cells have less stringent requirements for matching the genetics of recipients).

Background on the use of cord blood stem cell transplants in HIV cure research and the possibilities of identifying matches for people of different races can be found in an overview article published in 2015 by Lawrence Petz and colleagues. [3]

Comment

Although this woman also had to undergo chemotherapy and whole body irradiation, this new case has significant differences to some of the stem cell procedures used by the Berlin, London and Dusseldorf cure cases.

This included a suggestion that the use of cord cells could have been the reason that graft-vs-host disease was not experienced in this case.

However, an earlier paediatric case using cord blood cells was unfortunately not successful when the 12 year old boy died from graft-vs-host disease. The cases are not easy to compare though because of both age and more advanced ill health. [4]

It is significant that this case was a women, and also from a mixed race background where matching donors becomes significantly more difficult.

The use of cord stem cells was also reported to reduce the stringency needed with adult donors, although fewer cells available needed to an adult relative donor to contribute to the overall transplant.

Source

Jefferys R. CROI 2022 Update: A New Potential HIV Cure Case; Broadly Neutralizing Antibody Enhances Post-Treatment Control. TAG basic Science Blog. (15 February 2022)

https://tagbasicscienceproject.typepad.com/tags_basic_science_vaccin/2022/02/croi-2022-update-a-new-potential-hiv-cure-case-broadly-neutralizing-antibody-enhances-post-treatment.html 

By Richard Jefferys, TAG

References

1. Bryson Y et al. HIV-1 remission with CCR5∆32∆32 haplo-cord transplant in a US woman: IMPAACT P1107. CROI 2022, 12–16 and 22–24 February, virtual meeting. Oral abstract 65.
   https://ww2.aievolution.com/cro2201/index.cfm?do=abs.viewAbs&abs=3310 (abstract)
   https://croi2022.onlineeventpro.freeman.com/live-stream/23875346/HIV-RESERVOIRS-AND-CURE-STRATEGIES (webcast)
2. Hsu J et al.  CCR5 delta32 cord & haploidentical grafts: allogeneic stem cell transplant for HIV+ /AML patient: a case report from the IMPAACT P1107 observational study. Blood 2018; 132 (Supplement 1): 2184. doi: 10.1182/blood-2018-99-117734
   https://doi.org/10.1182/blood-2018-99-117734
3. Petz LD et al. Progress toward curing HIV infection with hematopoietic cell transplantation. Stem Cells Cloning. 2015;8:109-116. DOI: 10.2147/SCCAA.S56050.
   https://www.dovepress.com/progress-toward-curing-hiv-infection-with-hematopoietic-cell-transplan-peer-reviewed-fulltext-article-SCCAA
4. Rothenberger M et al. Transplantation of CCR5∆32 homozygous umbilical cord blood in a child with acute lymphoblastic leukemia and perinatally acquired HIV infection, Open Forum Infectious Diseases 5(5) ofy090, DOI: 10.1093/ofid/ofy090. (May 2018).
   https://academic.oup.com/ofid/article/5/5/ofy090/5001531

All HIV i-Base reports from CROI 2022.

SEE ALSO:

• UCLA Health at CROI: Presenting the case of a woman with HIV-1 in remission following specialized stem cell transplantation for leukemia
• NIH: Researchers document third known case of HIV remission involving stem cell transplant
• Aidsmap: New York woman is free of HIV 14 months after stem cell transplant
• POZ: New York woman may be cured of HIV after stem cell transplant
• Medscape: A third person living with HIV has been cured by transplant
• Healio: US woman is third person to achieve sustained HIV remission after stem cell transplant