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

Berta Torres, Alberto C Guardo, Lorna Leal, Agathe Leon, Constanza Lucero, Miriam J Alvarez-Martinez, Miguel J Martinez, Jordi Vila, María Martínez-Rebollar, Ana González-Cordón, Josep M Gatell, Montserrat Plana, Filipe García

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.

(Published: 29 September 2014)

Citation: Torres B et al. Journal of the International AIDS Society 2014, 17:19246

http://www.jiasociety.org/index.php/jias/article/view/19246 | http://dx.doi.org/10.7448/IAS.17.1.19246




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