Persistence of HIV After Allogeneic Bone Marrow Transplant in a Dually Infected Individual.

AIDS Research and Human Retroviruses
Adam A CapoferriChristine M Durand

Abstract

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.

References

Feb 14, 2009·The New England Journal of Medicine·Gero HütterEckhard Thiel
Jun 24, 2011·Journal of Clinical Microbiology·Andrew D ReddUNKNOWN Rakai Health Sciences Program
Aug 13, 2015·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Christine JohnstonAnn Woolfrey
Feb 1, 2019·Nature·Katherine M BrunerRobert F Siliciano
Mar 6, 2019·Nature·Ravindra K GuptaEduardo Olavarria
Jul 8, 2019·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Richard F AmbinderJoseph C Alvarnas

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