Evidence map›Paper›PMID 26938995›Full record

ArticlePLoS pathogens2016

Integrated and Total HIV-1 DNA Predict Ex Vivo Viral Outgrowth.

Maja Kiselinova, Ward De Spiegelaere, Maria Jose Buzon, Eva Malatinkova, Mathias Lichterfeld, Linos Vandekerckhove

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
9.9field-weighted citation impact, top 2% 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

67 citing papers in PubMed, 95 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. HIV Reservoir: How to Measure It?Current HIV/AIDS reports · 2023
    Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Mucosal integrin α4β7 blockade fails to reduce the seeding and size of viral reservoirs in SIV-infected rhesus macaques.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
    Article
  18. Article
  19. Article
  20. Article

7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Maja KiselinovaHIV Translational Research Unit (HTRU), Department of Internal Medicine, Ghent University and Ghent University Hospital, Ghent, Belgium.
Ward De SpiegelaereHIV Translational Research Unit (HTRU), Department of Internal Medicine, Ghent University and Ghent University Hospital, Ghent, Belgium.
Maria Jose BuzonRagon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America.
Eva MalatinkovaHIV Translational Research Unit (HTRU), Department of Internal Medicine, Ghent University and Ghent University Hospital, Ghent, Belgium.
Mathias LichterfeldRagon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America.
Linos VandekerckhoveHIV Translational Research Unit (HTRU), Department of Internal Medicine, Ghent University and Ghent University Hospital, Ghent, Belgium.
Ghent University Hospital · BEMassachusetts General Hospital · USRagon Institute of MGH, MIT and Harvard · US

Funding

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
Limiting HIV-1 persistence by targeting stem cell properties of CD4 T cellsR21AI106468 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI LICHTERFELD, MATHIAS · 2013 to 2014
$465k
NIAID NIH HHS AI098487NIAID NIH HHS AI106468NIAID NIH HHS R21 AI106468
6 · The paper itself

Abstract

The persistence of a reservoir of latently infected CD4 T cells remains one of the major obstacles to cure HIV. Numerous strategies are being explored to eliminate this reservoir. To translate these efforts into clinical trials, there is a strong need for validated biomarkers that can monitor the reservoir over time in vivo. A comprehensive study was designed to evaluate and compare potential HIV-1 reservoir biomarkers. A cohort of 25 patients, treated with suppressive antiretroviral therapy was sampled at three time points, with median of 2.5 years (IQR: 2.4-2.6) between time point 1 and 2; and median of 31 days (IQR: 28-36) between time point 2 and 3. Patients were median of 6 years (IQR: 3-12) on ART, and plasma viral load (<50 copies/ml) was suppressed for median of 4 years (IQR: 2-8). Total HIV-1 DNA, unspliced (us) and multiply spliced HIV-1 RNA, and 2LTR circles were quantified by digital PCR in peripheral blood, at 3 time points. At the second time point, a viral outgrowth assay (VOA) was performed, and integrated HIV-1 DNA and relative mRNA expression levels of HIV-1 restriction factors were quantified. No significant change was found for long- and short-term dynamics of all HIV-1 markers tested in peripheral blood. Integrated HIV-1 DNA was associated with total HIV-1 DNA (p<0.001, R² = 0.85), us HIV-1 RNA (p = 0.029, R² = 0.40), and VOA (p = 0.041, R2 = 0.44). Replication-competent virus was detected in 80% of patients by the VOA and it correlated with total HIV-1 DNA (p = 0.039, R² = 0.54). The mean quantification difference between Alu-PCR and VOA was 2.88 log10, and 2.23 log10 between total HIV-1 DNA and VOA. The levels of usHIV-1 RNA were inversely correlated with mRNA levels of several HIV-1 restriction factors (TRIM5α, SAMHD1, MX2, SLFN11, pSIP1). Our study reveals important correlations between the viral outgrowth and total and integrated HIV-1 DNA measures, suggesting that the total pool of HIV-1 DNA may predict the size of the replication-competent virus in ART suppressed patients.

Indexed as

Virus IntegrationAdultCohort StudiesDisease ReservoirsDNA, ViralFemaleHIV-1HIV InfectionsHumansLinear ModelsMaleMiddle AgedRNA, ViralViral LoadDNA, ViralRNA, Viral

Identifiers

PMID26938995
PMCPMC4777389
OpenAlexW2291085800

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.