Reversal of monocyte and macrophage activation and the relationship to viral suppression and T cell activation are unknown in patients with advanced HIV-1
infection, initiating antiretroviral
therapy. This study aimed to determine whether reduction in
biomarkers of monocyte and macrophage activation would be reduced in conjunction with viral suppression and resolution of T cell activation. Furthermore, we hypothesized that the addition of CCR5 antagonism (by
maraviroc) would mediate greater reduction of monocyte/macrophage activation markers than suppressive antiretroviral
therapy alone. In the CCR5 antagonism to decrease the incidence of
immune reconstitution inflammatory syndrome study, antiretroviral
therapy-naïve patients received
maraviroc or placebo in addition to standard antiretroviral
therapy. PBMCs and plasma from 65 patients were assessed during 24 wk of antiretroviral
therapy for
biomarkers of monocyte and macrophage activation. Markers of monocyte and macrophage activation were reduced significantly by 24 wk, including CD14(++)CD16(+) intermediate monocytes (P < 0.0001), surface CD163 (P = 0.0004), CD169 (P < 0.0001),
tetherin (P = 0.0153), and soluble CD163 (P < 0.0001). A change in CD38(+),
HLA-DR(+) CD8 T cells was associated with changes in CD169 and
tetherin expression.
Maraviroc did not affect
biomarkers of monocyte/macrophage activation but resulted in greater percentages of CCR5-positive monocytes in PBMC. HIV-1 suppression after 24 wk of antiretroviral
therapy, with or without
maraviroc, demonstrates robust recovery in monocyte subset activation markers, whereas soluble markers of activation demonstrate minimal decrease, qualitatively differentiating markers of monocyte/macrophage activation in advanced disease.