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).

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