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Interleukin-6 and D-dimer levels at seroconversion as predictors of HIV-1 disease progression

Hamlyn, Elizabetha,b; Fidler, Saraha; Stöhr, Wolfgangc; Cooper, David A.d; Tambussi, Giuseppee; Schechter, Maurof; Miro, Jose M.g; Mcclure, Myraa; Weber, Jonathana; Babiker, Abdelc; Porter, Kholoudc; for SPARTAC Trial Investigators

doi: 10.1097/QAD.0000000000000155
Clinical Science: Concise Communications

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).

Conclusion: IL-6 levels at time of HIV-1 seroconversion independently predict HIV-1 disease progression in patients with primary HIV-1 infection.

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.

Correspondence to Dr Elizabeth Hamlyn, Caldecot Centre, Kings College Hospital, London SE5 9RS, UK. Tel: +44 20 3299 3852; fax: +44 20 3299 3486; e-mail: e.hamlyn@nhs.net

Received 30 August, 2013

Revised 14 October, 2013

Accepted 14 October, 2013

© 2014 Lippincott Williams & Wilkins, Inc.