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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 hematologic malignancies and... Full description

Journal Title: AIDS research and human retroviruses 2021 (ja)
Main Author: Capoferri, Adam A
Other Authors: Redd, Andrew D , Gocke, Christopher D , Clark, Laura R , Ambinder, Richard F , Durand, Christine
Format: Electronic Article Electronic Article
Language: English
Quelle: Alma/SFX Local Collection
ID: ISSN: 0889-2229
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title: 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
ispartof: AIDS research and human retroviruses, 2021 (ja)
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 hematologic malignancies and HIV (ClinicalTrials.gov, NCT01836068), we measured HIV reservoirs longitudinally using a quantitative viral outgrowth assay. We sequenced the RT-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 timepoints 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 hematologic malignancies and HIV (ClinicalTrials.gov, NCT01836068), we measured HIV reservoirs longitudinally using a quantitative viral outgrowth assay. We sequenced the RT-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 timepoints 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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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 hematologic malignancies and HIV (ClinicalTrials.gov, NCT01836068), we measured HIV reservoirs longitudinally using a quantitative viral outgrowth assay. We sequenced the RT-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 timepoints 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.
doi10.1089/AID.2021.0047