The relationship between markers of monocyte/macrophage activation (sCD14 and sCD163) and components of the Veterans Aging Cohort Study (VACS) score, which predict mortality in patients with HIV, in immunologic nonresponders (INRs) is not defined. HIV(+) subjects with >12 months of continuous virologic suppression and persistent CD4 <250 cells/mm(3) were enrolled at the CORE Center, Chicago. Subjects had a single visit where history was taken and blood drawn. ELISA assays for sCD14 and sC163 were performed at Blood Systems, CA. Descriptive statistics were performed using SAS. We enrolled 43 subjects with persistent CD4 <250 after a median of 32 months of continuous viral suppression. We found elevated markers of monocyte/macrophage activation; sCD14 and sCD163 correlated with higher VACS scores as well as hepatitis C virus (HCV) coinfection and FIB-4 score, components of the VACS index. In this cohort of immunologic nonresponders, there was a significant correlation between markers of monocyte/macrophage activation and the VACS score. Among components of the VACS index, we did not find a significant association between HCV coinfection and sCD14; however, there was a significant association between HCV coinfection and sCD163.