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Longitudinal analysis of viral dynamics in HIV+-to-HIV+ HOPE Act kidney-transplant recipients
Tatianna Travieso, … , Cameron Robert Wolfe, Maria Blasi
Tatianna Travieso, … , Cameron Robert Wolfe, Maria Blasi
Published September 10, 2024
Citation Information: J Clin Invest. 2024;134(20):e181560. https://doi.org/10.1172/JCI181560.
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Clinical Research and Public Health AIDS/HIV Article has an altmetric score of 7

Longitudinal analysis of viral dynamics in HIV+-to-HIV+ HOPE Act kidney-transplant recipients

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Abstract

BACKGROUND The HIV Organ Policy Equity (HOPE) Act allows individuals living with HIV to accept organs from donors with HIV. This practice widens the pool of available organs, but also presents important virological issues, including the potential for HIV superinfection of the recipient, viral persistence in the kidney, and loss of virological control.METHODS We addressed these issues by performing in-depth longitudinal viral sequence analyses on urine, blood, and urine-derived renal epithelial cells from 12 recipients of HIV+ kidney allografts.RESULTS We amplified donor-derived HIV-1 env sequences in 5 out of 12 recipients after transplant. These donor-derived env sequences were amplified from recipient urine, urine-derived renal epithelial cells, and plasma between 12 and 96 hours after transplant and remained detectable up to 16 days after transplant. Env sequences were also detected in kidney biopsies taken from the allografts before implantation in 6 out of the 12 transplant cases, indicating the presence of donor virus within the organ. One recipient had a viremic episode 3.5 years after transplantation as a result of antiretroviral therapy (ART) interruption. Only recipient strain viral sequences were detected in blood, suggesting that the donor virus, if still present, was not reactivated during the temporary ART withdrawal.CONCLUSIONS This study demonstrates that the HIV env sequences in a donor kidney can be amplified from biopsies taken from the allograft before implantation and can be detected transiently in blood and urine samples collected from the organ recipients after transplantation.FUNDING National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant number R01DK131497.

Authors

Tatianna Travieso, Hannah Stadtler, Naseem Alavian, Feng Gao, Mary Klotman, Cameron Robert Wolfe, Maria Blasi

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Figure 1

Phylogenetic tree analysis of HIV env sequences amplified from Hope 1 recipient before and up to 5 years after kidney transplant.

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Phylogenetic tree analysis of HIV env sequences amplified from Hope 1 re...
(A) Neighbor-joining phylogenetic tree that includes all of the HIV envelope sequences amplified from blood, urine, and LN samples obtained from the kidney-transplant recipient with HIV before and up to 5 years after transplantation of a kidney from a donor with HIV. Two separate viral lineages (lineages 1 and 2) were identified in the recipient up to 16 days after transplantation. Bootstrap values over 80% are indicated. (B) All the HIV quasispecies in lineage 1 that were amplified from the recipient’s urine (solid blue triangles for cell-free viral RNA and green squares for viral DNA associated with RTE cells) and plasma (solid orange circles) between 12 hours and 16 days after transplantation are genetically related to the donor virus (open shapes) and genetically distant from the viral sequences amplified from the recipient’s PBMCs, plasma, LNs, and urine-derived RTE cells before transplantation. Several HIV env sequences were also amplified from the kidney biopsy taken from the allograft before implantation (open pink diamonds), the majority of which were compartmentalized from the rest of samples analyzed (P value of 0.016 using a codon-based test of positive selection). The asterisk demarks a group of HIV envelope sequences amplified from either donor urine or recipient urine collected after transplantation that clustered separately from blood-derived sequences.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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