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Short Communication: Persistence of HIV After Allogeneic Bone Marrow Transplant in a Dually Infected Individual

Allogeneic bone marrow transplant (alloBMT) with continuous antiretroviral therapy alone has not been shown to completely eradicate HIV, possibly due to HIV persistence in rare residual host cells or infection of donor cells. Within a trial of alloBMT in individuals with hematological malignancies a... Full description

Journal Title: AIDS research and human retroviruses 2022, Vol.38 (1), p.33-36
Main Author: Capoferri, Adam A
Other Authors: Redd, Andrew D , Gocke, Christopher D , Clark, Laura R , Ambinder, Richard F , Durand, Christine M
Format: Electronic Article Electronic Article
Language: English
Subjects:
HIV
Quelle: Alma/SFX Local Collection
Publisher: United States: Mary Ann Liebert, Inc., publishers
ID: ISSN: 0889-2229
Link: https://www.ncbi.nlm.nih.gov/pubmed/34107771
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title: Short Communication: Persistence of HIV After Allogeneic Bone Marrow Transplant in a Dually Infected Individual
format: Article
creator:
  • Capoferri, Adam A
  • Redd, Andrew D
  • Gocke, Christopher D
  • Clark, Laura R
  • Ambinder, Richard F
  • Durand, Christine M
subjects:
  • Anti-Retroviral Agents - therapeutic use
  • Antiretroviral agents
  • Antiretroviral therapy
  • Bone marrow
  • Bone Marrow Transplantation
  • CD4-Positive T-Lymphocytes
  • Hematopoietic Stem Cell Transplantation
  • HIV
  • HIV Infections - complications
  • HIV Infections - drug therapy
  • Human immunodeficiency virus
  • Humans
  • Immunology
  • Infections
  • Phylogeny
  • Replication
  • RNA-directed DNA polymerase
  • Sequence analysis
  • Stem cell transplantation
  • Syngeneic grafts
  • Viral Load
  • Viruses
ispartof: AIDS research and human retroviruses, 2022, Vol.38 (1), p.33-36
description: Allogeneic bone marrow transplant (alloBMT) with continuous antiretroviral therapy alone has not been shown to completely eradicate HIV, possibly due to HIV persistence in rare residual host cells or infection of donor cells. Within a trial of alloBMT in individuals with hematological malignancies and HIV (ClinicalTrials.gov, NCT01836068), we measured HIV reservoirs longitudinally using a quantitative viral outgrowth assay. We sequenced the reverse transcriptase region of pol for replication-competent virus and performed maximum-likelihood phylogenetic reconstruction. Replacement of host cells was measured using short-tandem repeats. In one participant who had ≥99.5% donor cell replacement, HIV reservoirs declined from 2.2 infectious units per million to undetectable levels at post-alloBMT time points except for week 64. Sequence analysis revealed dual infection pre-alloBMT. Replication-competent virus isolated at week 64 post-alloBMT was identical to a pre-alloBMT variant. This report provides proof-of-concept that minor replication-competent HIV variants can persist at low levels despite ≥99.5% donor cell engraftment post-alloBMT.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0889-2229
fulltext: fulltext
issn:
  • 0889-2229
  • 1931-8405
url: Link


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descriptionAllogeneic bone marrow transplant (alloBMT) with continuous antiretroviral therapy alone has not been shown to completely eradicate HIV, possibly due to HIV persistence in rare residual host cells or infection of donor cells. Within a trial of alloBMT in individuals with hematological malignancies and HIV (ClinicalTrials.gov, NCT01836068), we measured HIV reservoirs longitudinally using a quantitative viral outgrowth assay. We sequenced the reverse transcriptase region of pol for replication-competent virus and performed maximum-likelihood phylogenetic reconstruction. Replacement of host cells was measured using short-tandem repeats. In one participant who had ≥99.5% donor cell replacement, HIV reservoirs declined from 2.2 infectious units per million to undetectable levels at post-alloBMT time points except for week 64. Sequence analysis revealed dual infection pre-alloBMT. Replication-competent virus isolated at week 64 post-alloBMT was identical to a pre-alloBMT variant. This report provides proof-of-concept that minor replication-competent HIV variants can persist at low levels despite ≥99.5% donor cell engraftment post-alloBMT.
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subjectAnti-Retroviral Agents - therapeutic use ; Antiretroviral agents ; Antiretroviral therapy ; Bone marrow ; Bone Marrow Transplantation ; CD4-Positive T-Lymphocytes ; Hematopoietic Stem Cell Transplantation ; HIV ; HIV Infections - complications ; HIV Infections - drug therapy ; Human immunodeficiency virus ; Humans ; Immunology ; Infections ; Phylogeny ; Replication ; RNA-directed DNA polymerase ; Sequence analysis ; Stem cell transplantation ; Syngeneic grafts ; Viral Load ; Viruses
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abstractAllogeneic bone marrow transplant (alloBMT) with continuous antiretroviral therapy alone has not been shown to completely eradicate HIV, possibly due to HIV persistence in rare residual host cells or infection of donor cells. Within a trial of alloBMT in individuals with hematological malignancies and HIV (ClinicalTrials.gov, NCT01836068), we measured HIV reservoirs longitudinally using a quantitative viral outgrowth assay. We sequenced the reverse transcriptase region of pol for replication-competent virus and performed maximum-likelihood phylogenetic reconstruction. Replacement of host cells was measured using short-tandem repeats. In one participant who had ≥99.5% donor cell replacement, HIV reservoirs declined from 2.2 infectious units per million to undetectable levels at post-alloBMT time points except for week 64. Sequence analysis revealed dual infection pre-alloBMT. Replication-competent virus isolated at week 64 post-alloBMT was identical to a pre-alloBMT variant. This report provides proof-of-concept that minor replication-competent HIV variants can persist at low levels despite ≥99.5% donor cell engraftment post-alloBMT.
copUnited States
pubMary Ann Liebert, Inc., publishers
pmid34107771
doi10.1089/aid.2021.0047
orcididhttps://orcid.org/0000-0002-6048-2115