TY - JOUR
T1 - Short Communication
T2 - Persistence of HIV after Allogeneic Bone Marrow Transplant in a Dually Infected Individual
AU - Capoferri, Adam A.
AU - Redd, Andrew D.
AU - Gocke, Christopher D.
AU - Clark, Laura R.
AU - Ambinder, Richard F.
AU - Durand, Christine M.
N1 - Publisher Copyright:
© Copyright 2022, Mary Ann Liebert, Inc., publishers 2022.
PY - 2022/1
Y1 - 2022/1
N2 - 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.
AB - 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.
KW - HIV latent reservoir
KW - HIV persistence
KW - allogeneic bone marrow transplant
KW - dual infection
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U2 - 10.1089/aid.2021.0047
DO - 10.1089/aid.2021.0047
M3 - Article
C2 - 34107771
AN - SCOPUS:85122812771
SN - 0889-2229
VL - 38
SP - 33
EP - 36
JO - AIDS research and human retroviruses
JF - AIDS research and human retroviruses
IS - 1
ER -