Systemic Inflammation, Coagulation, and Clinical Risk in the START Trial

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Baker , J V , Sharma , S , Grund , B , Rupert , A , Metcalf , J A , Schechter , M , Munderi , P , Aho , I , Emery , S , Babiker , A , Phillips , A , Lundgren , J D , Neaton , J D , Lane , H C & INSIGHT START Strategic Timing 2017 , ' Systemic Inflammation, Coagulation, and Clinical Risk in the START Trial ' , Open Forum Infectious Diseases , vol. 4 , no. 4 , 262 . https://doi.org/10.1093/ofid/ofx262

Title: Systemic Inflammation, Coagulation, and Clinical Risk in the START Trial
Author: Baker, Jason V.; Sharma, Shweta; Grund, Birgit; Rupert, Adam; Metcalf, Julia A.; Schechter, Mauro; Munderi, Paula; Aho, Inka; Emery, Sean; Babiker, Abdel; Phillips, Andrew; Lundgren, Jens D.; Neaton, James D.; Lane, H. Clifford; INSIGHT START Strategic Timing
Contributor: University of Helsinki, Department of Medicine
Date: 2017
Language: eng
Number of pages: 9
Belongs to series: Open Forum Infectious Diseases
ISSN: 2328-8957
URI: http://hdl.handle.net/10138/231542
Abstract: Background. The Strategic Timing of AntiRetroviral Treatment (START) trial demonstrated that immediate (at CD4+ > 500 cells/mu L) vs deferred (to CD4+ Methods. Biomarkers were measured from stored plasma prior to randomization and at month 8. Associations of baseline biomarkers with event risk were estimated with Cox regression, pooled across groups, adjusted for age, gender, and treatment group, and stratified by region. Mean changes over 8 months were estimated and compared between the immediate and deferred ART arms using analysis of covariance models, adjusted for levels at entry. Results. Baseline biomarker levels were available for 4299 START participants (92%). Mean follow-up was 3.2 years. Higher levels of IL-6 and D-dimer were the only biomarkers associated with risk for AIDS, SNA or death, as well as the individual components of SNA and AIDS events (HRs ranged 1.37-1.41 per 2-fold higher level), even after adjustment for baseline CD4+ count, HIV RNA level, and other biomarkers. At month 8, biomarker levels were lower in the immediate arm by 12%-21%. Conclusions. These data, combined with evidence from prior biomarker studies, demonstrate that IL-6 and D-dimer consistently predict clinical risk across a broad spectrum of CD4 counts for those both ART-naive and treated. Research is needed to identify disease-modifying treatments that target inflammation beyond the effects of ART.
Subject: coagulation
comorbidities
end-organ disease
HIV disease
inflammation risk
HIV-INFECTED PATIENTS
C-REACTIVE PROTEIN
ANTIRETROVIRAL THERAPY
D-DIMER
CIRCULATING MARKERS
PLASMA-LEVELS
BIOMARKERS
COHORT
AIDS
ACTIVATION
3121 General medicine, internal medicine and other clinical medicine
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