Although antiretroviral treatment lowers the burden of human immunodeficiency virus (HIV)-related disease,it does not always result in immunological recovery.This manifests as persistent chronic inflammation,immune activation or exhaustion that can promote the onset of co-morbidities.As the exact function of regulatory T (Treg) cells in HIV remains unclear,this cross-sectional study investigated three expression markers (Forkhead box protein P3[FOXP3],glycoprotein A repetitions predominant[GARP],special AT-rich sequence binding protein 1[SATB 1]) and compared their expansion between CD4+CD25-and CD4+CD25++ T cells.Age-matched study subjects were recruited (Western Cape,South Africa) and sub-divided:HIV-negative subjects (n =12),HIV-positive naive treated (n =22),HIV-positive treated based on CD4 count cells/μL (CD4 ＞ 500 and CD4 ＜ 500) (n =34) and HIV-treated based on viral load (VL) copies/mL(VL ＜ 1000 and VL ＞ 1000) (n =34).Markers of immune activation (CD38) and coagulation (CD142) on T cells (CD8)were assessed by flow cytometry together with FOXP3,GARP and SATB 1 expression on CD4+CD25-and CD4+CD25++ T cells.Plasma levels of interleukin-10 (IL-10;anti-inflammatory marker),IL-6 (inflammatory marker) and D-dimer (coagu-lation marker) were assessed.This study revealed three major findings in immuno-compromised patients with virological failure (CD4 ＜ 500;VL ＞ 1000):(1) the expansion of the unconventional Treg cell subset (CD4+CD25-FOXP3+) is linked with disease progression markers;(2) increased GARP expression in the CD4+CD25-and CD4+CD25++ subsets;and (3) the identification of a strong link between CD4+CD25-SATB1+ cells and markers of immune activation (CD8+CD38+) and coagulation (CD8 +CD 142+ and D-dimer).