EXPERT REACTION: Stem cell transplant sends another HIV patient into remission
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2023-02-21 03:00
A patient who was treated for leukaemia with stem cell transplantation has also shown nine years of persistent suppression of HIV, according to international researchers, who say this patient could follow the famous ‘London patient’ and ‘Berlin patient’ who underwent similar treatments. The team describe the 53-year-old male with HIV who was diagnosed with acute myeloid leukaemia in January 2011. During his stem cell transplant for the cancer, he received bone marrow from a donor with a mutation in the gene for the HIV-1 receptor CCR5, which makes cells resistant to HIV infection. HIV became undetectable in the patient's blood cells, so antiretroviral therapy was stopped in November 2018 to see if the infection would return, but the patient remained in remission for another four years. While stem cell therapy is a high-risk procedure, the team says this case study adds to previous work that could one day allow HIV treatment and remission.
Journal/conference: Nature Medicine
Link to research (DOI): 10.1038/s41591-023-02213-x
Organisation/s: Düsseldorf University Hospital, Germany
Funder: The IciStem program (www.icistem.org) is funded through the amfAR
Research Consortium on HIV Eradication program (amfAR 109858-
64-RSRL) and the Dutch Aidsfonds (P60802). University Hospital
Düsseldorf was supported by the Heinz Ansmann Foundation for AIDS
Research. The German Center for Infection Research (DZIF TTU 04.816,
04.819) supported University Hospital Cologne and the University Medical Center Hamburg-Eppendorf. J.S.z.W. was supported by the
European Research Council (ERC H2020 grant no. 681032), the H.W.
& J. Hector Foundation (project no. M2101), the German Research
Foundation (SFB1328 project A12) and Hamburg Investment and
Development Bank (IFB Hamburg, PROFI no. 51167035). F.P.-C. was
supported by Institut Pasteur’s Roux Cantarini program. T.H. and C.
Mummert were supported by the German Research Foundation,
Graduate School 1071, project B1. M.S. was given a grant by the
Miguel Servet Fellowship (CP22/00038) and I+D+I RTI-A project
(PID2020-115931RA-I00) from the Ministry of Science and Innovation.
Research in the Martínez-Picado laboratory is supported by the
Spanish Ministry of Science and Innovation (grant nos. PID2019-
109870RB-I00 and CB21/13/00063), NIH/NIAID (1 UM1 AI164561-01),
European Union HORIZON-HLTH-2021-DISEASE-04-07 (grant no.
101057100) and the Research Centers of Catalonia (grant no. 2017
SGR 252). C.G. was supported by the PhD fellowship of the Spanish
Ministry of Education, Culture and Sport (FPU15/03698). J.D.E. and
the Oregon National Primate Research Center were supported by the
NIH/NIAID (grant no. R01AI143411) and the NIH/Office of the Director
(grant no. P51OD011092), respectively. The funders had no role in
the conceptualization, design, data collection, analysis, decision
to publish or preparation of the paper. The authors thank IciStem
no. 019 and all volunteers who participated in this study; K. Pohl, E.
Bäcker, O. Adams, T. Feldt, F. Hüttig and N. Freise of University Hospital
Düsseldorf for their assistance with patient care and/or sample
logistics; S. Kummer and R. Woost of the University Medical Center
Hamburg-Eppendorf for technical assistance with sample preparation
and flow cytometry; M. Angin of Institut Pasteur for initial assistance
with flow cytometry analyses; G. Hütter of Cellex, J. L. Diez Martin
of Hospital Gregorio Marañón Madrid, J. Kuball, D. de Jong and M.
van Luin of the University Medical Center Utrecht for contributing
their expertise to the discussion; M. A. Fernandez Sanmartin, Flow
Cytometry Service of the Institut de Recerca Germans Trias i Pujol
for his contribution to the cytometry panel discussions and sample
sorting; Á. Hernandez Rodrıguez, V. González Soler and B. Rivaya
Sanchez of the Microbiology Department of the Hospital Universitari
Germans Trias i Pujol for their assistance with the murine outgrowth
assay and HIV antibodies; J. Diaz Pedroza and Y. Rosales of the
Comparative Medicine and Bioimage Centre of Catalonia for their
contribution to the development of the mVOA experiments; M. del
Carmen García and I. González of the AIDS Research Institute IrsiCaixa
for their assistance with the HIV-DNA ddPCR; J. Blankson of the Johns
Hopkins University for his contribution to the development of the
mVOA protocol; and the Oregon Health & Science University Knight
BioLibrary for the lymph node sample.
Media release
From: Springer Nature
Medicine: Sustained HIV-1 remission after stem cell transplantation
A recipient of an allogeneic hematopoietic stem cell transplant to treat leukemia has shown persistent suppression of human immunodeficiency virus type 1 (HIV-1) more than 9 years after the transplantation and 4 years after the suspension of anti-retroviral therapy. The results are reported in Nature Medicine this week.
Allogeneic hematopoietic stem cell transplantation (HSCT) is a procedure used to treat certain cancers, such as leukemia, by transferring immature blood cells from a donor to repopulate the bone marrow of the recipient. CCR5Δ32/Δ32 HSCT involves the transfer of cells from a donor with two copies of the Δ32 mutation in the gene encoding the HIV-1 co-receptor CCR5; such cells are resistant to HIV-1 infection. So far there have been two published cases of patients experiencing remission of HIV-1 after cancer treatment involving the transplantation of CR5Δ32/Δ32 hematopoietic stem cells: the ‘London patient’ and the ‘Berlin patient’.
Björn-Erik Jensen and colleagues now present a detailed longitudinal analysis of blood and tissue samples from a patient demonstrating remission of both leukemia and of detectable HIV-1 after transplantation of CR5Δ32/Δ32 hematopoietic stem cells. The patient, a 53-year-old male, was diagnosed as having acute myeloid leukemia in January 2011. The patient underwent transplantation of CR5Δ32/Δ32 stem cells from a female donor in February 2013, followed by chemotherapy and infusions of donor lymphocytes. After the transplantation, anti-retroviral therapy was continued, but pro-viral HIV-1 was undetectable in the patient’s blood cells. Anti-retroviral therapy was suspended in November 2018 with the patient’s informed consent, almost 6 years after the stem cell transplantation, to determine whether infectious HIV-1 persisted in the patient. The authors did not observe a resurgence of HIV-1 RNA or a boosting of the immune response to HIV-1 proteins that might have suggested a lingering, yet undetectable, viral reservoir 4 years after the suspension of anti-retroviral treatment.
The authors conclude that although HSCT remains a high-risk procedure that is at present an option only for some people living with both HIV-1 and hematological cancers, these results may inform future strategies for achieving long-term remission of HIV-1.
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