Evidence map›Paper›PMID 36596305›Full record

ArticleCell host & microbe2023

Progressive transformation of the HIV-1 reservoir cell profile over two decades of antiviral therapy.

Xiaodong Lian, Kyra W Seiger, Elizabeth M Parsons, Ce Gao, Weiwei Sun, Gregory T Gladkov, Isabelle C Roseto, Kevin B Einkauf, Matthew R Osborn, Joshua M Chevalier and 14 more

Abstract read
In one paragraph

Article in Cell host & microbe, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

86 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
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  6. Review
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  9. Article
  10. The HIV reservoir landscape in elite controllers.Current opinion in HIV and AIDS · 2026
    Review
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  14. Review
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26 more citing papers are in PubMed but not listed here.

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

24 authors.

Xiaodong LianInfectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Kyra W SeigerInfectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Elizabeth M ParsonsInfectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Ce GaoInfectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Weiwei SunRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Gregory T GladkovInfectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Isabelle C RosetoRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Kevin B EinkaufInfectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Matthew R OsbornInfectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Joshua M ChevalierInfectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Chenyang JiangInfectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Jane BlackmerInfectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Mary CarringtonRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA; Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Eric S RosenbergInfectious Disease Division, Massachusetts General Hospital, Boston, MA 02114, USA.
Michael M LedermanCase Western Reserve University, Cleveland, OH 44106, USA.
Deborah K McMahonUniversity of Pittsburgh, Pittsburgh, PA 15260, USA.
Ronald J BoschCenter for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Jeffrey M JacobsonCase Western Reserve University, Cleveland, OH 44106, USA.
Rajesh T GandhiInfectious Disease Division, Massachusetts General Hospital, Boston, MA 02114, USA.
Michael J PelusoDivision of HIV, Infectious Diseases and Global Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
Tae-Wook ChunLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Steven G DeeksDivision of HIV, Infectious Diseases and Global Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
Xu G YuInfectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Mathias LichterfeldInfectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA. Electronic address: mlichterfeld@partners.org.

Funding

Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1M
Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6M
Harvard Medical School Vaccine Clinical Trials UnitUM1AI069412 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI Lindsey Robert Baden, Daniel R. Kuritzkes · 2012 to 2026
$57.2M
University of Pittsburgh Clinical Trials UnitUM1AI069494 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SUSAN L KOLETAR, John W Mellors · 2012 to 2026
$38.0M
Pediatric Adolescent Virus Elimination (PAVE) Martin Delaney CollaboratoryUM1AI164566 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Ann M Chahroudi, Deborah Persaud · 2021 to 2026
$35.5M
BEAT-HIV: Delaney Collaboratory to Cure HIV-1 Infection by Combination ImmunotherapyUM1AI164570 · NIAID · WISTAR INSTITUTE · PI Luis J Montaner, James L. Riley · 2021 to 2026
$34.7M
Delaney AIDS Research Enterprise to Cure HIVUM1AI164560 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS, Sharon Ruth Lewin · 2021 to 2026
$32.0M
Role of Viral Reservoirs in the Pathogenesis of HIV DiseaseZIAAI000851 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CHUN, TAE-WOOK · 2009 to 2025
$29.3M
Effects of genetic polymorphism in MHC, KIR, and related loci on human diseaseZIABC010791 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI CARRINGTON, MARY N. · 2009 to 2025
$18.2M
Elite controllers as a model for a cure of HIV-1 infectionR37AI155171 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Xu Yu · 2020 to 2026
$5.2M
Novel single genome approaches to determine the mechanisms of HIV latent infection in blood, gut, and lymph nodesR01DK120387 · NIDDK · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI LICHTERFELD, MATHIAS, YUKL, STEVEN A · 2019 to 2023
$4.1M
Selection and Evolution of HIV-1 reservoir cells in blood and tissuesR01AI152979 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI ESTES, JACOB D, LICHTERFELD, MATHIAS · 2020 to 2025
$3.8M
NHLBI NIH HHS R01 HL134539NIAID NIH HHS K24 AI155233NIAID NIH HHS R01 AI130005NIAID NIH HHS R01 AI152979NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI069412NIAID NIH HHS UM1 AI069494NIAID NIH HHS UM1 AI164560NIAID NIH HHS UM1 AI164566NIAID NIH HHS UM1 AI164570NIDA NIH HHS R33 DA047034NIDA NIH HHS R61 DA047034NIDDK NIH HHS R01 DK120387
6 · The paper itself

Abstract

HIV-1 establishes a life-long reservoir of virally infected cells which cannot be eliminated by antiretroviral therapy (ART). Here, we demonstrate a markedly altered viral reservoir profile of long-term ART-treated individuals, characterized by large clones of intact proviruses preferentially integrated in heterochromatin locations, most prominently in centromeric satellite/micro-satellite DNA. Longitudinal evaluations suggested that this specific reservoir configuration results from selection processes that promote the persistence of intact proviruses in repressive chromatin positions, while proviruses in permissive chromosomal locations are more likely to be eliminated. A bias toward chromosomal integration sites in heterochromatin locations was also observed for intact proviruses in study participants who maintained viral control after discontinuation of antiretroviral therapy. Together, these results raise the possibility that antiviral selection mechanisms during long-term ART may induce an HIV-1 reservoir structure with features of deep latency and, possibly, more limited abilities to drive rebound viremia upon treatment interruptions.

Indexed as

HIV-1HIV InfectionsAnti-Retroviral AgentsAntiviral AgentsCD4-Positive T-LymphocytesHeterochromatinHumansProvirusesViral LoadVirus LatencyAnti-Retroviral AgentsAntiviral AgentsHeterochromatinblock and lockFLIP-seqHIVHIV cureHIV eradicationintegration siteslatencyMIP-seqpost-treatment controllersretroviral pathogenesis

Identifiers

PMID36596305
PMCPMC9839361

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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.