Differential Reduction in Monocyte Activation and Vascular Inflammation With Integrase Inhibitor-Based Initial Antiretroviral Therapy Among HIV-Infected Individuals

Abstract

Background: Little is known about how different antiretrovirals effect inflammation and monocyte activation in human immunodeficiency virus (HIV) infection.

Methods: We examined plasma specimens obtained during a randomized, double-blinded trial in antiretroviral therapy (ART)-naive HIV-infected adults which compared the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/c/FTC/TDF) with that of efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). From a random sample achieving an HIV type 1 RNA load of <50 copies/mL by week 48, changes over 24 and 48 weeks in levels of biomarkers of monocyte activation (soluble CD14 [sCD14] and soluble CD163 [sCD163]), systemic inflammation (soluble tumor necrosis factor α receptor I [sTNF-RI], interleukin 6 [IL-6], and high-sensitivity C-reactive protein [hsCRP]), and vascular inflammation (lipoprotein-associated phospholipase A2 [Lp-PLA2]) were compared. Multivariable linear regression was used.

Results: A total of 200 participants were included. Significant differences favoring EVG/c/FTC/TDF were noted for changes in sCD14, hsCRP, and Lp-PLA2 levels. Factors independently associated with a larger decrease in the sCD14 level included random assignment to receive EVG/c/FTC/TDF, higher baseline sCD14 level, and larger decreases in hsCRP and sCD163 levels; factors associated with a larger Lp-PLA2 decrease included higher baseline Lp-PLA2 and IL-6 levels, smaller increases in total cholesterol and triglycerides levels, a larger decrease in the sCD14 level, and a smaller decrease in the sCD163 level.

Conclusions: EVG/c/FTC/TDF led to greater decreases in sCD14, hsCRP, and Lp-PLA2 levels, compared with EFV/FTC/TDF. Randomization group independently predicted the change in sCD14 level, and changes in monocyte activation independently predicted the change in Lp-PLA2 level. There appears to be a more favorable effect of the integrase inhibitor EVG over efavirenz on immune activation, which may affect vascular inflammation.

Keywords: HIV infection; antiretroviral-naive; monocyte activation; systemic inflammation; vascular inflammation.

Figure 1.

Median percentage changes (interquartile range) in biomarker levels over 24 and 48 weeks, by randomization group. P values are for comparisons between groups in the percentage change from weeks 0 to 24 and weeks 0 to 48. Abbreviations: EFV/FTC/TDF, efavirenz/emtricitabine/tenofovir disoproxil fumarate; EVG/c/FTC/TDF, elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate; hsCRP, high-sensitivity C-reactive protein; IL-6, interleukin 6; Lp-PLA₂, lipoprotein-associated phospholipase A₂; sCD14, soluble CD14; sCD163, soluble CD163; sTNF-RI, soluble tumor necrosis factor α receptor I.