High Cellular Monocyte Activation in People Living With Human Immunodeficiency Virus on Combination Antiretroviral Therapy and Lifestyle-Matched Controls Is Associated With Greater Inflammation in Cerebrospinal Fluid
Authors: Booiman Thijs , Wit Ferdinand W. , Maurer Irma , De Francesco Davide , Sabin Caroline A. , Harskamp Agnes M. , Prins Maria , Garagnani Paolo , Pirazzini Chiara , Franceschi Claudio , Fuchs Dietmar , Gisslén Magnus , Winston Alan , Reiss Peter , Kootstra Neeltje A. ,   On Behalf of the Comorbidity in Relation to AIDS (COBRA) Collaboration, Reiss P. , Wit F. W. N. M. , Schouten J. , Kooij K. W. , van Zoest R. A. , Elsenga B. C. , Janssen F. R. , Heidenrijk M. , Zikkenheiner W. , van der Valk M. , Kootstra N. A. , Booiman T. , Harskamp-Holwerda A. M. , Boeser-Nunnink B. , Maurer I. , Mangas Ruiz M. M. , Girigorie A. F. , Villaudy J. , Frankin E. , Pasternak A. , Berkhout B. , van der Kuyl T. , Portegies P. , Schmand B. A. , Geurtsen G. J. , ter Stege J. A. , Klein Twennaar M. , Majoie C. B. L. M. , Caan M. W. A. , Su T. , Weijer K. , Bisschop P. H. L. T. , Kalsbeek A. , Wezel M. , Visser I. , Ruhé H. G. , Franceschi C. , Garagnani P. , Pirazzini C. , Capri M. , Dall’Olio F. , Chiricolo M. , Salvioli S. , Hoeijmakers J. , Pothof J. , Prins M. , Martens M. , Moll S. , Berkel J. , Totté M. , Kovalev S. , Gisslén M. , Fuchs D. , Zetterberg H. , Winston A. , Underwood J. , McDonald L. , Stott M. , Legg K. , Lovell A. , Erlwein O. , Doyle N. , Kingsley C. , Sharp D. J. , Leech R. , Cole J. H. , Zaheri S. , Hillebregt M. M. J. , Ruijs Y. M. C. , Benschop D. P. , Burger D. , de Graaff-Teulen M. , Guaraldi G. , Bürkle A. , Sindlinger T. , Moreno-Villanueva M. , Keller A. , Sabin C. , de Francesco D. , Libert C. , Dewaele S. 
Published: May 2017

Background

Increased monocyte activation and intestinal damage have been shown to be predictive for the increased morbidity and mortality observed in treated people living with human immunodeficiency virus (PLHIV).

Methods

A cross-sectional analysis of cellular and soluble markers of monocyte activation, coagulation, intestinal damage, and inflammation in plasma and cerebrospinal fluid (CSF) of PLHIV with suppressed plasma viremia on combination antiretroviral therapy and age and demographically comparable HIV-negative individuals participating in the Comorbidity in Relation to AIDS (COBRA) cohort and, where appropriate, age-matched blood bank donors (BBD).

Results

People living with HIV, HIV-negative individuals, and BBD had comparable percentages of classical, intermediate, and nonclassical monocytes. Expression of CD163, CD32, CD64, HLA-DR, CD38, CD40, CD86, CD91, CD11c, and CX3CR1 on monocytes did not differ between PLHIV and HIV-negative individuals, but it differed significantly from BBD. Principal component analysis revealed that 57.5% of PLHIV and 62.5% of HIV-negative individuals had a high monocyte activation profile compared with 2.9% of BBD. Cellular monocyte activation in the COBRA cohort was strongly associated with soluble markers of monocyte activation and inflammation in the CSF.

Conclusions

People living with HIV and HIV-negative COBRA participants had high levels of cellular monocyte activation compared with age-matched BBD. High monocyte activation was predictive for inflammation in the CSF.