Background:  High levels of inflammatory (interleukin-6 [IL-6], high-sensitivity C-reactive protein [hsCRP], and coagulation biomarkers, e.g., D-dimer) are associated with an increased risk of morbidity and mortality in HIV⁺ patients. We wished to assess the effect on these biomarkers of the switch from enfuvirtide (ENF) to raltegravir (RAL) in well-suppressed patients.

Methods:  In the EASIER trial, 169 highly treatment-experienced patients with plasma HIV RNA <400 copies/mL under an ENF-based regimen were randomized to immediate or deferred switch from ENF to RAL. At week 24, patients in the deferred arm switched to RAL and patients in the immediate arm remained on RAL as long as week 48. Levels of IL-6, hsCRP, and D-dimer in stored plasma samples were measured at baseline, week 24 and week 48.

Results:   Plasma samples from 164 patients were analysed (see the table). At baseline, 84% of patients were male, median age was 48 years, median CD4 count was 389/mL, 86% of the patients had plasma HIV RNA <50 copies/mL, patients had received ENF for a median of 2.5 years, and median levels of IL-6, hsCRP, and D-Di were similar in both arms. At week 24, levels of biomarkers were significantly lower in the immediate arm vs the deferred arm for IL6 (p <0.0001), hsCRP (p = 0.0003), and D-dimer (p <0.0001), Wilcoxon rank-sum test. In the immediate arm, median levels of all biomarkers decreased between baseline and week 24, with no change between week 24 and week 48. In the deferred arm, no changes were noted between baseline and week 24, but median levels of all biomarkers decreased between week 24 and week 48, reaching similar levels in both arms at week 48.

Median biomarker levels in the immediate vs delayed switch (IQR)

Conclusions:   IL-6, hsCRP, and D-dimer levels significantly decreased after switching from ENF to RAL in HIV⁺ patients well suppressed under ART.