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

Research output: Contribution to journalJournal articleResearchpeer-review


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  • Jason V Baker
  • Shweta Sharma
  • Birgit Grund
  • Adam Rupert
  • Julia A Metcalf
  • Mauro Schechter
  • Paula Munderi
  • Inka Aho
  • Sean Emery
  • Abdel Babiker
  • Andrew Phillips
  • Jens D Lundgren
  • James D Neaton
  • H Clifford Lane
  • INSIGHT START (Strategic Timing of AntiRetroviral Treatment) Study Group
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Background: The Strategic Timing of AntiRetroviral Treatment (START) trial demonstrated that immediate (at CD4+ >500 cells/µL) vs deferred (to CD4+ <350 cells/µL or AIDS) antiretroviral therapy (ART) initiation reduced risk for AIDS and serious non-AIDS (SNA). We investigated associations of inflammation, coagulation, and vascular injury biomarkers with AIDS, SNA or death, and the effect of immediate ART initiation.

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-naïve and treated. Research is needed to identify disease-modifying treatments that target inflammation beyond the effects of ART.

Original languageEnglish
JournalOpen Forum Infectious Diseases
Issue number4
Pages (from-to)ofx262
Publication statusPublished - 2017

    Research areas

  • Journal Article

ID: 52584907