Protease inhibitor monotherapy is associated with a higher level of monocyte activation, bacterial translocation and inflammation

Abstract

Introduction Monotherapy with protease‐inhibitors (MPI) may be an alternative to cART for HIV treatment. We assessed the impact of this strategy on immune activation, bacterial translocation and inflammation. Methods We performed a cross‐sectional study comparing patients on successful MPI (n=40) with patients on cART (n=20). Activation, senescence, exhaustion and differentiation stage in CD4+ and CD8+ T lymphocyte subsets, markers of monocyte activation, microbial translocation, inflammation, coagulation and low‐level viremia were assessed. Results CD4+ or CD8+ T lymphocyte subset parameters were not significantly different between both groups. Conversely, as compared with triple cART, MPI patients showed a higher proportion of activated monocytes (CD14+ CD16−CD163+ cells, p=0.031), soluble markers of monocyte activation (sCD14 p=0.004, sCD163 p=0.002), microbial translocation (lipopolysaccharide (LPS)‐binding protein; LBP p=0.07), inflammation (IL‐6 p=0.04) and low‐level viremia (p=0.035). In a multivariate model, a higher level of CD14+ CD16−CD163+ cells and sCD14, and presence of very low‐level viremia were independently associated with MPI. Monocyte activation was independently associated with markers of inflammation (IL‐6, p=0.006), microbial translocation (LBP, p=0.01) and low‐level viremia (p=0.01). Conclusions Patients on MPI showed a higher level of monocyte activation than patients on standard therapy. Microbial translocation and low‐level viremia were associated with the high level of monocyte activation observed in patients on MPI. The long‐term clinical consequences of these findings should be assessed.

Keywords

• protease inhibitor
• monotherapy
• immune activation
• very low‐level viremia
• microbial translocation
• monocyte