Evidence map›Paper›PMID 26431315›Full record

ArticlePloS one2015

Comparative Analysis of Cell-Associated HIV DNA Levels in Cerebrospinal Fluid and Peripheral Blood by Droplet Digital PCR.

Michelli Faria de Oliveira, Sara Gianella, Scott Letendre, Konrad Scheffler, Sergei L Kosakovsky Pond, Davey M Smith, Matt Strain, Ronald J Ellis

Open access · goldAbstract readComparative Study
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

23 citing papers in PubMed, 28 citations in OpenAlex.

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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

8 authors at 2 institutions in 2 countries.

Michelli Faria de OliveiraUniversity of California, San Diego, La Jolla, California, United States of America.
Sara GianellaUniversity of California, San Diego, La Jolla, California, United States of America.
Scott LetendreHIV Neurobehavioral Research Center, University of California, San Diego, San Diego, California, United States of America.
Konrad SchefflerUniversity of California, San Diego, La Jolla, California, United States of America; Stellenbosch University, Stellenbosch, South Africa.
Sergei L Kosakovsky PondUniversity of California, San Diego, La Jolla, California, United States of America.
Davey M SmithUniversity of California, San Diego, La Jolla, California, United States of America; Veterans Affairs San Diego Healthcare System, San Diego, United States of America.
Matt StrainUniversity of California, San Diego, La Jolla, California, United States of America.
Ronald J EllisHIV Neurobehavioral Research Center, University of California, San Diego, San Diego, California, United States of America.
University of California, San Diego · USStellenbosch University · ZA

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
Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS · 1988 to 2026
$93.6M
VirologyP30AI036214 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Maile Ann Young Karris · 1994 to 2026
$78.4M
STRUCTURAL NEUROIMAGING COREP30MH062512 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DAVID J MOORE · 2001 to 2026
$50.4M
Transmission ProbabilityP01AI074621 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LITTLE, SUSAN JANET · 2008 to 2012
$23.1M
Primary Infection Resource Consortium (PIRC)R24AI106039 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LITTLE, SUSAN JANET · 2013 to 2021
$23.1M
Southern California Primary Infection ProgramU01AI043638 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RICHMAN, DOUGLAS D · 1998 to 2010
$21.3M
San Diego Clinical and Translational Research InstituteUL1TR000100 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S · 2012 to 2015
$19.7M
HOPE Training GrantT32AI007384 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Sara Gianella Weibel, Scott L Letendre · 1990 to 2026
$9.7M
Prospective Memory in HIV-1 InfectionR01MH073419 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WOODS, STEVEN PAUL · 2005 to 2017
$6.6M
Interdisciplinary Research Fellowship in NeuroAIDSR25MH081482 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MARIANA CHERNER · 2007 to 2026
$5.2M
Molecular Epidemiology for HIV Prevention for Drug Users and Other Risk Groups DP1DA034978 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SMITH, DAVID MITCHELL · 2012 to 2016
$4.1M
NCATS NIH HHS UL1 TR000100NCATS NIH HHS UL1TR000100NIAID NIH HHS 7-UM1 AI068636-07NIAID NIH HHS AI007384NIAID NIH HHS AI027763NIAID NIH HHS AI036214NIAID NIH HHS AI074621NIAID NIH HHS AI100665NIAID NIH HHS AI106039NIAID NIH HHS AI43638NIAID NIH HHS K24 AI100665NIAID NIH HHS P01 AI074621NIAID NIH HHS P30 AI027763NIAID NIH HHS P30-AI027763NIAID NIH HHS P30 AI036214NIAID NIH HHS R24 AI106039NIAID NIH HHS T32 AI007384NIAID NIH HHS U01 AI043638NIAID NIH HHS UM1 AI068636NIDA NIH HHS DA034978NIDA NIH HHS DP1 DA034978NIMH NIH HHS MH097520NIMH NIH HHS MH101012NIMH NIH HHS P30 MH062512NIMH NIH HHS P30-MH62512NIMH NIH HHS R01 MH073419NIMH NIH HHS R01-MH073419NIMH NIH HHS R01 MH097520NIMH NIH HHS R01 MH101012NIMH NIH HHS R25 MH081482NIMH NIH HHS R25-MH081482
6 · The paper itself

Abstract

backgroundMeasurement of HIV DNA-bearing cells in cerebrospinal fluid (CSF) is challenging because few cells are present. We present a novel application of the sensitive droplet digital (dd)PCR in this context.

methodsWe analyzed CSF cell pellets and paired peripheral blood mononuclear cells (PBMC) from 28 subjects, 19 of whom had undetectable HIV RNA (<48 copies/mL) in both compartments. We extracted DNA from PBMC using silica-based columns and used direct lysis on CSF cells. HIV DNA and the host housekeeping gene (RPP30) were measured in CSF and PBMC by (dd)PCR. We compared HIV DNA levels in virally-suppressed and-unsuppressed subgroups and calculated correlations between HIV DNA and RNA levels in both compartments using non-parametric tests.

resultsHIV DNA was detected in 18/28 (64%) CSF cell pellets, including 10/19 (53%) samples with undetectable HIV RNA. HIV DNA levels in CSF cell pellets were not correlated with RPP30 (p = 0.3), but correlated positively with HIV RNA in CSF (p = 0.04) and HIV DNA in PBMC (p = 0.03). Cellular HIV DNA in CSF was detected in comparable levels in HIV RNA-suppressed and unsuppressed subjects (p = 0.14). In contrast, HIV DNA levels in PBMC were significantly lower in HIV RNA-suppressed than in unsuppressed subjects (p = 0.014). Among subjects with detectable HIV DNA in both compartments, HIV DNA levels in CSF were significantly higher than in PBMC (p<0.001).

conclusionsDespite low mononuclear cell numbers in CSF, HIV DNA was detected in most virally suppressed individuals. In contrast to PBMC, suppressive ART was not associated with lower HIV DNA levels in CSF cells, compared to no ART, perhaps due to poorer ART penetration, slower decay of HIV DNA, or enrichment of HIV DNA-bearing mononuclear cells into the CSF, compared to blood. Future studies should determine what fraction of HIV DNA is replication-competent in CSF leukocytes, compared to PBMC.

Indexed as

Anti-HIV AgentsAntiretroviral Therapy, Highly ActiveCD4-Positive T-LymphocytesCerebrospinal FluidDNA, ViralHIV-1HIV InfectionsHumansLeukocytes, MononuclearOrgan SpecificityPolymerase Chain ReactionRetrospective StudiesRNA, ViralViral LoadViremiaVirus ReplicationAnti-HIV AgentsDNA, ViralRNA, Viral

Identifiers

PMID26431315
PMCPMC4592012
OpenAlexW2191187517

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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.