Evidence map›Paper›PMID 29868623›Full record

ArticleOpen forum infectious diseases2018

Transplantation of CCR5∆32 Homozygous Umbilical Cord Blood in a Child With Acute Lymphoblastic Leukemia and Perinatally Acquired HIV Infection.

Meghan Rothenberger, John E Wagner, Ashley Haase, Douglas Richman, Bartosz Grzywacz, Matthew Strain, Steven Lada, Jacob Estes, Courtney V Fletcher, Anthony T Podany and 5 more

Open access · goldAbstract read
In one paragraph

Article in Open forum infectious diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.4field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 18 citations in OpenAlex.

  1. Research Toward a Cure for Perinatal HIV.Clinics in perinatology · 2024
    Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Review
  9. Review
  10. On the Road to a HIV Cure: Moving Beyond Berlin and London.Infectious disease clinics of North America · 2019
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 1 country.

Meghan RothenbergerDepartment of Medicine, University of Minnesota, Minneapolis, Minnesota.
John E WagnerDepartment of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
Ashley HaaseDepartment of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota.
Douglas RichmanVeteran's Affairs (VA) San Diego Healthcare System, San Diego, California.
Bartosz GrzywaczCenter for AIDS Research, University of California San Diego, La Jolla, California.
Matthew StrainVeteran's Affairs (VA) San Diego Healthcare System, San Diego, California.
Steven LadaDepartment of Pathology and Lab Medicine, University of Minnesota, Minneapolis, Minnesota.
Jacob EstesAIDS and Cancer Virus Program and Laboratory Animal Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
Courtney V FletcherCollege of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska.
Anthony T PodanyCollege of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska.
Jodi AndersonDepartment of Medicine, University of Minnesota, Minneapolis, Minnesota.
Thomas SchmidtDepartment of Medicine, University of Minnesota, Minneapolis, Minnesota.
Steve WietgrefeDepartment of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota.
Timothy SchackerDepartment of Medicine, University of Minnesota, Minneapolis, Minnesota.
Michael R VernerisDepartment of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
University of Minnesota · USUniversity of Nebraska Medical Center · USVA San Diego Healthcare System · USLeidos (United States) · USUniversity of California, San Diego · US

Funding

Trial Design and Biostatistical Support CoreP01CA065493 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Mark J Osborn · 1995 to 2026
$48.2M
Viral reservoirs and sanctuaries in HAART - treated patients: role and mechanismsU19AI096109 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SCHACKER, TIMOTHY W · 2011 to 2015
$29.5M
First-in-human study of two anti-SARS CoV-2 antibodies in health volunteersUM1AI126620 · NIAID · WISTAR INSTITUTE · PI MONTANER, LUIS J, RILEY, JAMES L. · 2016 to 2021
$24.5M
Collaboratory of AIDS Researchers for Eradication (CARE)UM1AI126619 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MARGOLIS, DAVID M. · 2016 to 2020
$23.2M
Virological Measurements of Cryptic ReplicationP01AI074340 · NIAID · UNIVERSITY OF MINNESOTA · PI SCHACKER, TIMOTHY W · 2008 to 2012
$12.1M
The Lymphoid Tissue Pharmacology of Antiretroviral DrugsR01AI124965 · NIAID · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI FLETCHER, COURTNEY V · 2016 to 2020
$3.7M
Lymphoid Tissue Inducer/NK22 Cells and Post-transplant Immune RecoveryR01AI100879 · NIAID · UNIVERSITY OF MINNESOTA · PI VERNERIS, MICHAEL R. · 2013 to 2017
$1.9M
CCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001ENCI NIH HHS P01 CA065493NIAID NIH HHS P01 AI074340NIAID NIH HHS R01 AI100879NIAID NIH HHS R01 AI124965NIAID NIH HHS U19 AI096109NIAID NIH HHS UM1 AI126620
6 · The paper itself

Abstract

backgroundAllogeneic hematopoietic cell transplantation (allo-HCT) in a CCR5∆32 homozygous donor resulted in HIV cure. Understanding how allo-HCT impacts the HIV reservoir will inform cure strategies.

methodsA 12-year-old with perinatally acquired, CCR5-tropic HIV and acute lymphoblastic leukemia underwent myeloablative conditioning and umbilical cord blood (UCB) transplantation from a CCR5∆32 homozygous donor. Peripheral blood mononuclear cells (PBMCs) and the rectum were sampled pre- and post-transplant. The brain, lung, lymph node (LN), stomach, duodenum, ileum, and colon were sampled 73 days after transplantation (day +73), when the patient died from graft-vs-host disease. Droplet digital polymerase chain reaction (ddPCR) and in situ hybridization (ISH) were used detect the HIV reservoir in tissues. CCR5 and CD3 expression in the LN was assessed using immunohistochemistry (IHC).

resultsHIV DNA (vDNA) was detected in PBMCs by ddPCR pretransplant but not post-transplant. vDNA was detected by ISH in the rectum at days -8 and +22, and in the LN, colon, lung, and brain day +73. vDNA was also detected in the lung by ddPCR. IHC revealed CCR5+CD3+ cells in the LN postmortem.

conclusionsHIV was detected in multiple tissues 73 days after CCR5∆32 homozygous UCB allo-HCT despite myeloablative conditioning and complete donor marrow engraftment. These results highlight the importance of analyzing tissue during HIV cure interventions and inform the choice of assay used to detect HIV in tissue reservoirs.

Indexed as

allogeneic bone marrow transplantationCCR5∆32HIV cureHIV reservoirs

Identifiers

PMID29868623
PMCPMC5965100
OpenAlexW2803234785

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.