The Düsseldorf patient HIV cure case published in Nature Medicine
10 March 2023. Related: Cure-related research.
Richard Jefferys, TAG
On 20 February 2023, the news was awash with stories about the Düsseldorf Patient, one of five people considered likely cured of HIV after receipt of a stem cell transplant to treat a life-threatening cancer diagnosis.
As with all five reported cases to date, the stem cell donor was homozygous for the CCR5delta-32 mutation, which renders immune cells resistant to most HIV variants.
The media coverage has been prompted by the publication of a detailed report in the journal Nature Medicine by Björn-Erik Ole Jensen and colleagues. [1]
The individual, who identified himself as Marc in an interview with a Dutch news outlet in 2021, has now been off antiretroviral therapy (ART) for four years with no sign of HIV viral load rebound. His current health is reported to be good, although the paper makes clear his journey has been difficult having experienced two relapses of acute myeloid leukemia and reactivation of multiple chronic viral infections (cytomegalovirus, herpes simplex virus 2, human herpesvirus 8 and Epstein–Barr virus). Mild chronic graft-versus-host disease of the eyes with bilateral keratoconjunctivitis sicca (dry eye syndrome) developed after the stem cell transplant and is still present.
The news headlines are potentially confusing because some state Marc is the third case to reflect the chronological sequence (after Timothy Ray Brown and Adam Castillejo) while others designate him the fifth to reflect the total number of cases described to date, which include two more recent examples in New York City and at the City of Hope in Los Angeles. [3, 4]
The first scientific description of the Düsseldorf Patient was in a poster presentation at the 2016 Conference on Retroviruses and Opportunistic Infections (CROI), prior to interruption of ART. [5]
Two post-interruption follow up posters were presented at CROI in 2019 and 2020. [6, 7]
The HIV cure research field has thus been aware of the case for a long time, and there was frustration and confusion last year when the announcement of a fifth similar possible HIV cure at the City of Hope mistakenly referred to it as the fourth based on the unnecessarily prim rationale that information on the Düsseldorf Patient hadn’t yet been published in a journal. [8]
Today’s publication will hopefully put any uncertainty to rest.
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Shortly after this paper in Nature Medicine, the New York City case was published as an open access paper in the journal Cell. [9]
A summary of this case includes that:
- First mixed-race woman with HIV-1 remission post CCR5Δ32/Δ32 haplo-cord transplant.
- 100% immune reconstitution by CCR5Δ32/Δ32 cord graft and resistance to HIV strains.
- No HIV viral rebound ≥18 months off antiretroviral therapy without graft vs. host disease.
- No detectable HIV-1 DNA/RNA, replication competent virus & loss of HIV Ab response.
Source
Jefferys R. The Düsseldorf patient HIV cure case published in Nature Medicine. TAG. (20 February 2023).
https://tagbasicscienceproject.typepad.com/tags_basic_science_vaccin/2023/02/the-düsseldorf-patient-hiv-cure-case-published-in-nature-medicine.html
References
- Jensen, BE.O., Knops, E., Cords, L. et al. In-depth virological and immunological characterization of HIV-1 cure after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation. Nat Med (2023). https://doi.org/10.1038/s41591-023-02213-x
https://www.nature.com/articles/s41591-023-02213-x - https://www.nrc.nl/nieuws/2021/12/10/hij-is-de-derde-mens-ter-wereld-die-genas-van-hiv-2-a4068420
- France 24. Third patient cured of HIV after receiving stem cell cancer treatment. (20 February 2023).
https://www.france24.com/en/europe/20230220-third-patient-cured-of-hiv-after-receiving-stem-cell-cancer-treatment - ABC News. 5th person confirmed to be cured of HIV. (20 February 2023).
https://abcnews.go.com/Health/5th-person-confirmed-cured-hiv/story?id=97323361 - Kobbe G et al. Treatment of HIV and AML by Allogeneic CCR5-d32 Blood Stem-Cell Transplantation. CROI 2016. Poster abstract 364.
https://www.croiconference.org/abstract/treatment-hiv-and-aml-allogeneic-ccr5-d32-blood-stem-cell-transplantation - Jensen B-E O et al. Analytic treatment interruption (ATI) after allogeneic CCR5-D32 HSCT for AML im 2013. CROI 2019. Poster abstract 394.
https://www.croiconference.org/abstract/analytic-treatment-interruption-ati-after-allogeneic-ccr5-d32-hsct-aml-2013 - Jensen B-E O et al. CCR5Δ32 SCT-induced HIV remission: traces of HIV DNA but fading immune reactivity. CROI 2020. Poster abstract 348.
https://www.croiconference.org/abstract/ccr5%ce%b432-sct-induced-hiv-remission-traces-of-hiv-dna-but-fading-immune-reactivity - Patient with HIV achieves remission following stem cell transplant at City of Hope. (27 July 2022).
https://www.cityofhope.org/hiv-patient-achieves-remission-following-stem-cell-transplant-city-of-hope -
Hsu J et al. HIV-1 remission and possible cure in a woman after haplo-cord blood transplant. Cell 186(6):1115-1126.e8. (16 March 2023)
This report was first posted on 21 February 2023. It was updated on 16 March to include the NYC case.