Reduced soluble CD14 levels after switching from a dual regimen with lamivudine plus boosted protease inhibitors to lamivudine plus dolutegravir in virologically suppressed HIV-infected patients

摘要

Background: HIV-induced systemic immune activation and inflammation have been associated with morbidity and mortality in virologically suppressed patients. Objective: To evaluate the impact of treatment switch from a dual regimen with lamivudine (3TC) plus ritonavir-boosted protease inhibitors (PI/r) to 3TC plus dolutegravir (DTG) on the monocyte activation marker soluble CD14 (sCD14) and other inflammatory biomarkers, interleukin-6 (IL-6), C-reactive protein (CRP), intestinal fatty acid-binding protein (I-FABP) and D-dimer. Methods: We performed a retrospective case-crossover study on integrase inhibitors-na?ve virologically suppressed patients while on 3TC + PI/r dual maintenance therapy for >48 weeks who switched to 3TC + DTG and maintained this regimen for >48weeks. Biomarkers plasma levels were tested by ELISA assays on stored samples at three time points: at switch (BL), 48weeks before (—48W) and 48weeks after switch (+48 W). Results: A total of 67 patients were included. Median sCD14 levels were stable from -48W to BL (from 6.07 to 6.04 log10 pg/mL, p = 0.235) but showed a statistically significant decrease after switch: from 6.04 (IQR 5.92-6.12) at BL to 5.95 (IQR 5.84-6.07) log10 pg/mL at + W48 (p< 0.001). Concurrently, an improvement in lipid profile was observed, even thought it was not correlated to the change in sCD14. The levels of IL-6, CRP, I-FABP and D-dimer remained stable before and after the switch to 3TC + DTG. Conclusions: In virologically suppressed HIV-infected patients on a 3TC + PI/r dual therapy, switching to 3TC + DTG was associated with a significant decline in sCD14. These data suggest reduced monocyte activation following substitution of boosted PI with DTG, which could have important clinical implications.