Early changes in coagulation but not inflammatory biomarkers under intermittent ART: the randomized ANRS 106 WINDOW trial

Introduction: In the SMART trial, baseline plasma hsCRP, IL6 and D-dimer levels were strongly correlated to all-cause mortality. A case-control study has shown an increase of IL-6 and D-dimer levels after one month of antiretroviral therapy (ART) interruption, which was correlated to viral load. Restarting ART was associated to a decrease in D-dimer but not IL-6 or hsCRP levels. We assessed biomarkers levels up to 96 weeks in ART-experienced adults with plasma HIV RNA levels <400 c/mL randomized in the ANRS 106 WINDOW trial to intermittent ART (IT: six cycles of eight weeks of ART interruption followed by eight weeks of ART) versus continuous treatment (CT). Methods: Stored plasma for 160 participants (80 IT and 80 CT), matched by age, sex and CDC classification, were analyzed blinded for IL-6, sCD-14, hsCRP and D-dimer levels at baseline, week 8 (IT group only), week 16 and week 96. Lower levels of detection for IL-6, sCD14, hsCRP and D-Dimer were 1.5 pg/mL, 250 ng/mL, 0.03 µg/mL and 0.21 µg/mL, respectively. The primary objective was to compare changes in IL-6, hsCRP, sCD14 and D-dimer plasma levels from baseline to week 8, 16 and 96 in the IT and CT arms. Biomarkers levels were log10 transformed prior to analysis. Results: At baseline, patients were mostly men (86%), with a median age of 40 years, a CD4+ T-cell count of 768/mm3, have received a median of 4.7 years of ART and 85% had HIV RNA <50 c/mL. Proportion of patients with plasma HIV RNA levels