Evidence map›Paper›PMID 19349849›Full record

ArticleAIDS (London, England)2009

Increased mutations in Env and Pol suggest greater HIV-1 replication in sputum-derived viruses compared with blood-derived viruses.

Thor A Wagner, Nicole H Tobin, Jennifer L McKernan, Min Xu, Ann J Melvin, Kathleen M Mohan, Gerald H Learn, James I Mullins, Lisa M Frenkel

Open access · greenAbstract read
In one paragraph

Article in AIDS (London, England), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.4field-weighted citation impact, top 39% 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

7 citing papers in PubMed, 11 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

9 authors at 3 institutions in 1 country.

Thor A WagnerUniversity of Washington, Seattle, Washington, USA.
Nicole H Tobin
Jennifer L McKernan
Min Xu
Ann J Melvin
Kathleen M Mohan
Gerald H Learn
James I Mullins
Lisa M Frenkel
University of Washington · USSeattle Children's Hospital · USSeattle Children's Hospital · US

Funding

University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI Kenneth Sherr · 1988 to 2026
$104.9M
ZIPRASIDONE IN NORMAL HEPATIC FUNCTION SUBJECTS &IN HEPATIC DYSFUCTIN SUBJECTSM01RR000037 · NCRR · UNIVERSITY OF WASHINGTON · PI MCDONALD, RUTH C · 1985 to 2007
$33.8M
ACADEMIC PEDIATRIC INFECTIOUS DISEASET32HD007233 · NICHD · SEATTLE CHILDREN'S HOSPITAL · PI KEVIN B URDAHL · 1985 to 2026
$6.7M
Reservoirs of drug-resistant HIV-1R01AI058723 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI FRENKEL, LISA M · 2005 to 2009
$2.0M
Persistent HIV-1 Replication in the Respiratory Tract Despite ARTK23AI077357 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI WAGNER, THOR ANDREW · 2008 to 2012
$647k
Reservoirs of drug-resistant HIV-1R21AI058723 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI FRENKEL, LISA M · 2004 to 2004
$229k
Persistent Replication of HIV-1 in ChildrenK23AI058683 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI TOBIN, NICOLE H · 2004 to 2005
$173k
NCRR NIH HHS M01 RR000037NCRR NIH HHS M01RR-00037NIAID NIH HHS K23 AI058683NIAID NIH HHS K23 AI077357NIAID NIH HHS K23 K23AI077357-01NIAID NIH HHS P30 AI027757NIAID NIH HHS P30 AI27757NIAID NIH HHS R01 AI058723NIAID NIH HHS R21 AI058723NICHD NIH HHS T32 HD007233PHS HHS T32 HDO07233-24
6 · The paper itself

Abstract

objectiveLow-level HIV-1 replication may occur during antiretroviral therapy (ART) that suppresses plasma HIV-1 RNA to less than 50 copies/ml (suppressive ART). Antiretroviral drugs appear less effective in macrophages and monocytes compared with lymphocytes, both in vitro and as implied in vivo by greater viral evolution observed during suppressive ART. Our objective was to examine sputum, which is rich in macrophages, for evidence of increased HIV-1 replication compared with that in the blood during suppressive ART.

designA cross-sectional study during suppressive ART was performed, and HIV-1 DNA sequences derived from induced sputa and peripheral blood mononuclear cells were compared.

methodsMultiple sequences encoding HIV-1 reverse transcriptase, protease, and envelope were generated using single-genome sequencing. Reverse transcriptase and protease sequences were analyzed for genotypic drug resistance. The evolutionary distances of env sequences from the inferred most recent common ancestor of infection were calculated, and CXCR4 usage was predicted.

resultsNine hundred seventy bidirectional sequences from 11 individuals were analyzed. HIV-1 env and pol derived from sputa had greater frequency of drug-resistance mutations (P = 0.05), evolutionary divergence (P = 0.004), and tendency for CXCR4 usage (P = 0.1) compared with viruses derived from peripheral blood mononuclear cells.

conclusionThe greater frequency of HIV-1 drug-resistance mutations and divergence of HIV-1 env in sputa-derived viruses compared with peripheral blood mononuclear cell-derived viruses suggests greater HIV-1 replication in the respiratory tract compared with the blood. Characterization of viral evolution over time and by cell-type could identify cells that provide a sanctuary for low-level viral replication in the respiratory tract during suppressive ART.

Indexed as

AdolescentAnti-HIV AgentsChildCross-Sectional StudiesDrug Therapy, CombinationGenes, envGenes, polHIV-1HIV InfectionsHumansPlasmaRNA, ViralSputumVirus ReplicationAnti-HIV AgentsRNA, Viral

Identifiers

PMID19349849
PMCPMC2677633
OpenAlexW2068503851

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.