Abstract Since the advent of anti-retroviral (ARV) therapy, HIV-dementia has significantly declined, however, milder forms of HIV-associated Neurocognitive Disorder (HAND) remain highly prevalent. HIV DNA reservoirs in CD14+ Monocytes (MO) have been associated with cognitive impairment. However, the role of MO subsets in the pathogenesis of HAND over time remains poorly characterized. We sought to analyze HIV DNA content and MO phenotypic properties in relation to cognitive impairment through a prospective study of 30 ARV therapy-naïve individuals enrolled by HIV DNA reservoir levels with subsequent cognitive characterization as normal (n=17), Asymptomatic Neurocognitive Impairment (n=6), Mild Neurocognitive Disorder (MND) (n=2), HIV-associated dementia (HAD) (n=5) and 44 HIV- matched controls. HIV DNA was extracted from CD14+ cells and quantified by PCR. MO subsets and cell surface chemokine receptors were measured by flow cytometry using an extensive panel to exclude non-MO. Our preliminary findings show that among 4 MO subsets, there was a statistically significant decline in frequency of CD14highCD16+ (p<0.001) and an increase in CD14lowCD16- (p<0.001) in HIV+ compared to HIV- individuals. Remarkably, we found that CD14lowCD16+ MO frequency was lower in cognitively impaired individuals (p<0.05) and frequency of CCR2+ and CCR5+ expressing MO was higher in symptomatic (MND and HAD) cognitively impaired HIV+ individuals (p<0.05, p<0.05).