Evidence map›Paper›PMID 25959989›Full record

Trial reportHIV medicine2015

Pre-therapy inflammation and coagulation activation and long-term CD4 count responses to the initiation of antiretroviral therapy.

A C Achhra, A Phillips, S Emery, R D MacArthur, H Furrer, S De Wit, M Losso, M G Law, International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) Strategic Management of Antiretroviral Therapy (SMART) and Flexible Initial Retrovirus Suppressive Therapies (FIRST) study groups

Abstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in HIV medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
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.

A C AchhraKirby Institute, UNSW Australia, Sydney, NSW, Australia.
A PhillipsResearch Department of Infection & Population Health, University College London, London, UK.
S EmeryKirby Institute, UNSW Australia, Sydney, NSW, Australia.
R D MacArthurWayne State University, Detroit, MI, USA.
H FurrerInfectious Diseases, University Hospital, Bern, Switzerland.
S De WitDepartment of Infectious Diseases, CHU Saint-Pierre, Brussels, Belgium.
M LossoJ.M. Ramos Mejía Hospital, Buenos Aires, Argentina.
M G LawKirby Institute, UNSW Australia, Sydney, NSW, Australia.
International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) Strategic Management of Antiretroviral Therapy (SMART) and Flexible Initial Retrovirus Suppressive Therapies (FIRST) study groups

Funding

International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)U01AI068641 · NIAID · UNIVERSITY OF MINNESOTA · PI NEATON, JAMES DENNIS · 2006 to 2010
$120.1M
COMMUNITY PROGRAMS FOR CLINICAL RESEARCH ON AIDSU01AI046362 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI GORDIN, FRED M · 2000 to 2006
$75.9M
TERRY BEIRN COMMUNITY PROGRAMS FOR CLINICAL RESEARCH ONU01AI042170 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI NEATON, JAMES DENNIS · 1997 to 2006
$23.2M
Scholar Development Clinical Research (RMI)K12RR023247 · NCRR · UNIVERSITY OF MINNESOTA TWIN CITIES · PI LUEPKER, RUSSELL V · 2005 to 2009
$13.5M
Immune Reconstitution Syndrome in HIV infected Persons in Resource-Limited AreasK23AI073192 · NIAID · UNIVERSITY OF MINNESOTA · PI BOULWARE, DAVID R · 2009 to 2012
$530k
CCR NIH HHS HHSN261200800001CIntramural NIH HHSNCI NIH HHS HHSN261200800001ENCRR NIH HHS K12 RR023247NCRR NIH HHS K12RR023247-05NIAID NIH HHS K23 AI073192NIAID NIH HHS K23AI073192-02NIAID NIH HHS U01 AI042170NIAID NIH HHS U01AI042170NIAID NIH HHS U01 AI046362NIAID NIH HHS U01AI046362NIAID NIH HHS U01 AI068641NIAID NIH HHS U01AI068641NIAID NIH HHS U01AI46362
6 · The paper itself

Abstract

objectivesPre-antiretroviral therapy (ART) inflammation and coagulation activation predict clinical outcomes in HIV-positive individuals. We assessed whether pre-ART inflammatory marker levels predicted the CD4 count response to ART.

methodsAnalyses were based on data from the Strategic Management of Antiretroviral Therapy (SMART) trial, an international trial evaluating continuous vs. interrupted ART, and the Flexible Initial Retrovirus Suppressive Therapies (FIRST) trial, evaluating three first-line ART regimens with at least two drug classes. For this analysis, participants had to be ART-naïve or off ART at randomization and (re)starting ART and have C-reactive protein (CRP), interleukin-6 (IL-6) and D-dimer measured pre-ART. Using random effects linear models, we assessed the association between each of the biomarker levels, categorized as quartiles, and change in CD4 count from ART initiation to 24 months post-ART. Analyses adjusted for CD4 count at ART initiation (baseline), study arm, follow-up time and other known confounders.

resultsOverall, 1084 individuals [659 from SMART (26% ART naïve) and 425 from FIRST] met the eligibility criteria, providing 8264 CD4 count measurements. Seventy-five per cent of individuals were male with the mean age of 42 years. The median (interquartile range) baseline CD4 counts were 416 (350-530) and 100 (22-300) cells/μL in SMART and FIRST, respectively. All of the biomarkers were inversely associated with baseline CD4 count in FIRST but not in SMART. In adjusted models, there was no clear relationship between changing biomarker levels and mean change in CD4 count post-ART (P for trend: CRP, P = 0.97; IL-6, P = 0.25; and D-dimer, P = 0.29).

conclusionsPre-ART inflammation and coagulation activation do not predict CD4 count response to ART and appear to influence the risk of clinical outcomes through other mechanisms than blunting long-term CD4 count gain.

Indexed as

AdultAnti-HIV AgentsBiomarkersBlood CoagulationCD4 Lymphocyte CountC-Reactive ProteinDisease ProgressionFemaleFibrin Fibrinogen Degradation ProductsHIV InfectionsHumansInflammationInterleukin-6MalePredictive Value of TestsRetrospective StudiesAnti-HIV AgentsBiomarkersC-Reactive ProteinFibrin Fibrinogen Degradation Productsfibrin fragment DIL6 protein, humanInterleukin-6antiretroviral therapyCD4 countcoagulationC-reactive proteinD-dimerhighly active antiretroviral therapyHIVimmunological responseinflammationinterleukin-6

Identifiers

PMID25959989
PMCPMC5676307

What OpenQuestion holds

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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.