Evidence map›Paper›PMID 30688658›Full record

Trial reportThe Journal of clinical investigation2019

Intact HIV-1 proviruses accumulate at distinct chromosomal positions during prolonged antiretroviral therapy.

Kevin B Einkauf, Guinevere Q Lee, Ce Gao, Radwa Sharaf, Xiaoming Sun, Stephane Hua, Samantha My Chen, Chenyang Jiang, Xiaodong Lian, Fatema Z Chowdhury and 5 more

Open access · bronzeAbstract readClinical TrialMulticenter Study
In one paragraph

Trial report in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 222 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
222citing papers in PubMed, 1 pooled it
22.4field-weighted citation impact, top 1% 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

222 citing papers in PubMed, 1 synthesis or guideline pooled it, 313 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Manipulation of the cell cycle by HIV-1.Biochemical Society transactions · 2026
    Review
  6. Article
  7. Article
  8. The immunophenotype and proviral landscape of HIV-infected CD4 T cells during antiretroviral therapy.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. The HIV reservoir landscape in elite controllers.Current opinion in HIV and AIDS · 2026
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

162 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

15 authors at 5 institutions in 1 country.

Kevin B EinkaufInfectious Disease Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Guinevere Q LeeInfectious Disease Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Ce GaoRagon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.
Radwa SharafInfectious Disease Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Xiaoming SunRagon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.
Stephane HuaRagon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.
Samantha My ChenRagon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.
Chenyang JiangInfectious Disease Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Xiaodong LianInfectious Disease Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Fatema Z ChowdhuryRagon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.
Eric S RosenbergInfectious Disease Division, Massachusetts General Hospital, Boston, Massachusetts, USA.
Tae-Wook ChunNational Institute of Allergy and Infectious Diseases (NIAID), Bethesda, Maryland, USA.
Jonathan Z LiInfectious Disease Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Xu G YuInfectious Disease Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Mathias LichterfeldInfectious Disease Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Brigham and Women's Hospital · USRagon Institute of MGH, MIT and Harvard · USBroad Institute · USMassachusetts General Hospital · USNational Institute of Allergy and Infectious Diseases · US

Funding

The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ARTHUR Y KIM · 2004 to 2026
$94.4M
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
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
A Pilot Clinical Trial for HIV-1 EradicationU01AI117841 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI KURITZKES, DANIEL R., LICHTERFELD, MATHIAS · 2015 to 2020
$10.7M
Early Infant TreatmentU01AI114235 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI KURITZKES, DANIEL R., LICHTERFELD, MATHIAS · 2014 to 2020
$5.1M
Immunoregulatory Function of Myelomonocytic Receptors in HIV-1 InfectionR01AI078799 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI YU, XU · 2008 to 2017
$4.1M
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
Molecular profile of proviral reservoirs in HIV-infected drug usersR61DA047034 · NIDA · MASSACHUSETTS GENERAL HOSPITAL · PI LICHTERFELD, MATHIAS, YU, XU · 2018 to 2020
$3.4M
A systems biology approach to fingerprint HIV immune defense in Elite ControllersR01HL134539 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI YU, XU · 2016 to 2019
$3.3M
Proteomics and phosphoproteomics analysis in HIV-1 infectionR01AI130005 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI LICHTERFELD, MATHIAS · 2017 to 2021
$2.9M
Quantification of the HIV-1 Reservoir by Immuno-PCRR01AI120008 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI HEREDIA, ALONSO, LICHTERFELD, MATHIAS · 2015 to 2019
$1.9M
Inhibitors of host kinases as molecular targets for immune defense against HIV-1R01AI098487 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI LICHTERFELD, MATHIAS · 2012 to 2015
$1.7M
NHLBI NIH HHS R01 HL134539NIAID NIH HHS P30 AI060354NIAID NIH HHS R01 AI078799NIAID NIH HHS R01 AI098487NIAID NIH HHS R01 AI120008NIAID NIH HHS R01 AI130005NIAID NIH HHS R21 AI116228NIAID NIH HHS R21 AI122377NIAID NIH HHS R21 AI124776NIAID NIH HHS R33 AI116228NIAID NIH HHS R33 AI122377NIAID NIH HHS R56 AI125109NIAID NIH HHS U01 AI114235NIAID NIH HHS U01 AI117841NIAID NIH HHS UM1 AI126620NIDA NIH HHS R61 DA047034NIDDK NIH HHS R01 DK120387
6 · The paper itself

Abstract

Chromosomal integration of genome-intact HIV-1 sequences into the host genome creates a reservoir of virally infected cells that persists throughout life, necessitating indefinite antiretroviral suppression therapy. During effective antiviral treatment, the majority of these proviruses remain transcriptionally silent, but mechanisms responsible for viral latency are insufficiently clear. Here, we used matched integration site and proviral sequencing (MIP-Seq), an experimental approach involving multiple displacement amplification of individual proviral species, followed by near-full-length HIV-1 next-generation sequencing and corresponding chromosomal integration site analysis to selectively map the chromosomal positions of intact and defective proviruses in 3 HIV-1-infected individuals undergoing long-term antiretroviral therapy. Simultaneously, chromatin accessibility and gene expression in autologous CD4+ T cells were analyzed by assays for transposase-accessible chromatin using sequencing (ATAC-Seq) and RNA-Seq. We observed that in comparison to proviruses with defective sequences, intact HIV-1 proviruses were enriched for non-genic chromosomal positions and more frequently showed an opposite orientation relative to host genes. In addition, intact HIV-1 proviruses were preferentially integrated in either relative proximity to or increased distance from active transcriptional start sites and to accessible chromatin regions. These studies strongly suggest selection of intact proviruses with features of deeper viral latency during prolonged antiretroviral therapy, and may be informative for targeting the genome-intact viral reservoir.

Indexed as

Anti-Retroviral AgentsChromosomes, HumanFemaleHigh-Throughput Nucleotide SequencingHIV-1HIV InfectionsHumansMaleProvirusesTime FactorsAnti-Retroviral AgentsAIDS/HIVInfectious diseaseT cells

Identifiers

PMID30688658
PMCPMC6391088
OpenAlexW2912935425

What OpenQuestion holds

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Registered trials

None linked

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.