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The contribution of monocyte activation in the development of HIV-associated neurocognitive disorders is not completely understood. This study aimed to explore the predictive value of peripheral monocyte/macrophage (M/M) phenotypes on the evolution of cognitive performance in a population of virologically suppressed HIV-infected patients.Prospective, observational, longitudinal study.HIV-1-infected patients with HIV-RNA <50copies/mL for >12 months underwent neuropsychological examination at baseline and after 1 year. Cognitive performance was evaluated using Z-transformed scores, and neurocognitive impairment (NCI) was defined according to Frascati criteria. Peripheral M/M phenotypes (classic CD14++CD16−, intermediate CD14++CD16+, and nonclassic CD14+CD16++) and specific surface activation markers (eg, CD163, CD11b, and CD38) were evaluated using flow cytometry at baseline. Predictive value of peripheral M/M phenotypes on the evolution of cognitive performance over 1-year follow-up was also evaluated.Overall, 54 patients [85.2% men, median age 50 years (range 27–60 years), 27.8% hepatitis C virus coinfected, 48.1% with past AIDS-defining events, median nadir CD4 83 cells/μL (range 1–334), median baseline CD4 547 cells/μL (range 136–1652)] were enrolled. Proportion of patients with NCI was low, accounting for 13% at baseline and 16.5% after 1 year (P = 0.687). Memory was the only single domain in which decreased performance after 1 year was observed (−0.25 Z-score, P = 0.025). In patients with significant decrease (≥0.5 SD) in memory performance (n = 20), significantly lower CD14++CD16+CD163+ (% CD14++CD16+) (P = 0.038) and higher CD14+CD38+ (% CD14+) (P = 0.030) levels were observed.In virologically suppressed HIV-infected patients, the evolution of memory performance could be linked to the expression of certain peripheral activated M/M phenotypes. Such associations should be verified in larger populations over the long term.