title: Interleukin-6 and D-dimer levels at seroconversion as predictors of HIV-1 disease progression.
abstract: OBJECTIVE
  Inflammation and coagulation biomarkers interleukin (IL)-6 and D-dimer are predictive of all-cause mortality in chronic HIV-1 infection; however, their predictive value in individuals with recent infection has not been described.
  
  
  METHODS
  SPARTAC was a randomized controlled trial comparing three strategies of intervention in primary HIV-1 infection [no therapy, 12-week or 48-week antiretroviral therapy (ART)]. Plasma IL-6 and D-dimer were measured in 200 participants from sites in Australia, Brazil, UK and Italy. We evaluated age, sex/HIV risk group, time since HIV-1 seroconversion, baseline HIV-RNA, CD4 cell count and BMI as possible predictors of IL-6 and D-dimer levels at seroconversion using multivariable linear regression. For participants remaining ART-naive, we evaluated whether baseline IL-6 and D-dimer levels independently predicted time to reaching CD4 cell count less than 350 cells/μl or initiating ART using multivariable Cox proportional hazards models.
  
  
  RESULTS
  Median (interquartile range, IQR) baseline IL-6 and D-dimer levels were 1.45 (0.88-2.41) pg/ml and 0.34 (0.20-0.50) μg/l, respectively. Higher levels were associated with older age (P=0.008 and 0.004, respectively). Higher D-dimer levels were associated with higher HIV-RNA (P<0.001). For the 73 participants not initiating ART (median follow-up 225 weeks), of whom 48 reached the primary endpoint, higher baseline IL-6, but not D-dimer, was independently associated with a shorter time to primary endpoint [hazard ratio=1.38 per additional pg/ml, 95% confidence interval (CI) 1.09-1.75; P=0.007]. Other baseline predictors were older age (P=0.030), higher RNA (P=0.033) and lower CD4 cell count (P<0.001).
  
  
  CONCLUSIONS
  IL-6 levels at time of HIV-1 seroconversion independently predict HIV-1 disease progression in patients with primary HIV-1 infection.
authors.affiliation: aImperial College London bKings College Hospital NHS Foundation Trust cMedical Research Council Clinical Trials Unit at University College London, London, UK dKirby Institute, University of New South Wales, Sydney, New South Wales, Australia eOspedale San Raffaele, Milan, Italy fProjeto Praça Onze, Hospital Escola São Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil gHospital Clinic-Institut d'investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hamlyn
authors.forename: Sarah
authors.initials: S
authors.lastname: Fidler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stöhr
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tambussi
authors.forename: Mauro
authors.initials: M
authors.lastname: Schechter
authors.forename: Jose M
authors.initials: JM
authors.lastname: Miro
authors.forename: Myra
authors.initials: M
authors.lastname: Mcclure
authors.forename: Jonathan
authors.initials: J
authors.lastname: Weber
authors.forename: Abdel
authors.initials: A
authors.lastname: Babiker
authors.forename: Kholoud
authors.initials: K
authors.lastname: Porter
mesh_terms: D000328:Adult; D018450:Disease Progression; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D015658:HIV Infections / Q000175:diagnosis* / Q000473:pathology*; D006679:HIV Seropositivity; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; C036309:fibrin fragment D