Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation
Abstract
HIV entry into CD4(+) cells requires interaction with a cellular receptor, generally either CCR5 or CXCR4. We have previously reported the case of an HIV-infected patient in whom viral replication remained absent despite discontinuation of antiretroviral therapy after transplantation with CCR5Δ32/Δ32 stem cells. However, it was expected that the long-lived viral reservoir would lead to HIV rebound and disease progression during the process of immune reconstitution. In the present study, we demonstrate successful reconstitution of CD4(+) T cells at the systemic level as well as in the gut mucosal immune system after CCR5Δ32/Δ32 stem cell transplantation, while the patient remains without any sign of HIV infection. This was observed although recovered CD4(+) T cells contain a high proportion of activated memory CD4(+) T cells, ie, the preferential targets of HIV, and are susceptible to productive infection with CXCR4-tropic HIV. Furthermore, during the process of immune reconstitution, we found evidence for the replacement of long-lived host tissue cells with donor-derived cells, indicating that the size of the viral reservoir has been reduced over time. In conclusion, our results strongly suggest that cure of HIV has been achieved in this patient.
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The Berlin patient, an HIV-positive lymphoma patient transplanted with bone marrow from a CCR5-Δ32 homozygous donor, became cured with no demonstrable virus even 5 years after transplantation.
“Here, a HIV positive patient with lymphoma, who had been transplanted with bone marrow from a CCR5-Δ32 homozygous donor, became cured with no demonstrable virus even 5 years after transplantation, showing the potential benefits of CCR5 disruption [10,11].”
From Newer Gene Editing Technologies toward HIV Gene Therapy (2013) · cites this paper as [10]
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- Authors
- Allers, K., Hütter, G., Hofmann, J., Loddenkemper, C., Rieger, K., Thiel, E., & Schneider, T.
- Affiliations
- Stiftung Charité (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2011-03-10
- Volume
- 117
- Issue
- 10
- Pages
- 2791-2799
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2035813371
- Cited by
- 681
- References
- 52
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 13 · 2023: 22 · 2022: 38 · 2021: 22 · 2020: 46 · 2019: 45 · 2018: 45 · 2017: 51 · 2016: 62 · 2015: 73 · 2014: 72 · 2013: 81 · 2012: 59
- FWCI
- 18.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Keywords
- HIV cure, hematopoietic stem cell transplantation, HIV reservoir, viral rebound, immune reconstitution, CD4+ T cells, gut mucosal immunity, CXCR4-tropic HIV, memory T cells, antiretroviral therapy discontinuation
- MeSH terms
- Cell Separation, Flow Cytometry, Fluorescent Antibody Technique, Humans, Immunohistochemistry, Intestinal Mucosa, Leukemia, Myeloid, Acute, CD4-Positive T-Lymphocytes, HIV-1, HIV Infections, Immunity, Mucosal, Transplantation Conditioning, Receptors, CCR5, Stem Cell Transplantation
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