Abstract
BackgroundIncreased 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).MethodsA 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).ResultsPeople 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.ConclusionsPeople 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.
Highlights
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)
Treated people living with human immunodeficiency virus (PLHIV) are reported to have higher rates of ageassociated noncommunicable diseases (AANCCs) and a shorter average life expectancy compared with uninfected persons of the same age [1,2,3]
Markers of cellular monocyte activation did not differ between treated PLHIV and highly comparable, but Human Immunodeficiency Virus (HIV)-negative individuals (COBRA) but were notably increased in both PLHIV and HIV-negative Comorbidity in Relation to AIDS (COBRA) participants compared with blood bank donors (BBD)
Summary
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). The COBRA study included 134 PLHIV on cART and 79 demographically and lifestyle comparable HIV-negative control subjects from sites in London and Amsterdam in a detailed, prospective evaluation of the impact of HIV infection on the prevalence, incidence, and age at onset of AANCC. For the present immunological substudy, 40 PLHIV and 40 HIV-negative control participants were randomly selected with equal numbers in each of the following age groups: 45–50, 51–55, 56–60, 61–65, 66–70, and 70+, except for the oldest age category in which only a few individuals were available. Potential BBD were excluded from blood donation if they were determined to be at high risk of bloodborne infections (based on a questionnaire regarding general and sexual health, medication use, sexual risk behavior, and travel (https://www.sanquin.nl/en/give-blood/)
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