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

Booiman, Thijs; Wit, Ferdinand W. N. M.; Maurer, Irma; Francesco, Davide De; Sabin, Caroline; Harskamp, Agnes M.; Prins, Maria; Garagnani, Paolo; Pirazzini, Chiara; Franceschi, Claudio; Fuchs, Dietmar; Gisslén, Magnus; Winston, Alan; Reiss, Peter; Kootstra, Neeltje A.

doi:10.1093/ofid/ofx108

Cited by 18 publications

(29 citation statements)

References 56 publications

(58 reference statements)

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“…Baseline characteristics of the 40 people with HIV, 40 COBRA HIV-negative individuals and 35 blood donors have been described previously ( 16 , 17 ) and are summarized in Table 1 . Briefly, people with HIV and COBRA HIV-negative individuals had a median (IQR) age of 59 (54–64) years, blood donors had a median (IQR) age of 59 (52–65) years.…”

Section: Resultsmentioning

confidence: 99%

“…Monocytes from participants of the three study groups were analyzed for the percentages of classical, intermediate and non-classical monocyte subsets and the expression levels of activation markers (CD163, CD32, CD64, HLA-DR, CD38), T-cell costimulatory molecules (CD40 and CD86), and adhesion molecules (CD91, CD11c, and CX3CR1) ( 17 ).…”

Section: Resultsmentioning

confidence: 99%

“…For the present immunological sub-study, 40 people with HIV and 40 HIV-negative participants were randomly selected with equal numbers in each of the following age groups: 45–50 years, 51–55 years, 56–60 years, 61–65 years, 66–70 years, except for the oldest age category >70 years in which only a few individuals were available ( 16 , 17 ). Materials from 35 blood donors were obtained from the Dutch national blood bank in Amsterdam, the Netherlands ( ) ( 16 , 17 ). Blood donors were matched for age with the people with HIV and HIV-negative COBRA participants and were selected in such a way that the different COBRA age categories (other than the >70 years category) were equally represented.…”

Section: Methodsmentioning

confidence: 99%

“…Cryopreserved peripheral blood mononuclear cells (PBMCs) from COBRA participants and blood donors were used for immune phenotyping as described previously ( 16 , 17 ). PBMC were thawed and cell viability was analyzed by trypan blue staining and for FACS analysis cell viability was required to be >75%.…”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, increased levels of cellular monocyte activation were observed in a subset of individuals, which was the case for both the people with HIV and the otherwise comparable HIV-negative individuals. Furthermore, this high level of monocyte activation was associated with greater inflammation, both systemically and in the CSF ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

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Monocyte and T Cell Immune Phenotypic Profiles Associated With Age Advancement Differ Between People With HIV, Lifestyle-Comparable Controls and Blood Donors

et al. 2020

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Motivation People with HIV on successful antiretroviral therapy show signs of premature aging and are reported to have higher rates of age-associated comorbidities. HIV-associated immune dysfunction and inflammation have been suggested to contribute to this age advancement and increased risk of comorbidities. Method Partial least squares regression (PLSR) was used to explore associations between biological age advancement and immunological changes in the T cell and monocyte compartment in people with HIV (n=40), comparable HIV-negative individuals (n=40) participating in the Comorbidity in Relation to AIDS (COBRA) cohort, and blood donors (n=35). Results We observed that age advancement in all three groups combined was associated with a monocyte immune phenotypic profile related to inflammation and a T cell immune phenotypic associated with immune senescence and chronic antigen exposure. Interestingly, a unique monocyte and T cell immune phenotypic profile predictive for age advancement was found within each group. An inflammatory monocyte immune phenotypic profile associated with age advancement in HIV-negative individuals, while the monocyte profile in blood donors and people with HIV was more reflective of loss of function. The T cell immune phenotypic profile in blood donors was related to loss of T cell function, whereas the same set of markers were related to chronic antigen stimulation and immune senescence in HIV-negative individuals. In people with HIV, age advancement was related to changes in the CD4 + T cell compartment and more reflective of immune recovery after cART treatment. Impact The identified monocyte and T cell immune phenotypic profiles that were associated with age advancement, were strongly related to inflammation, chronic antigen exposure and immune senescence. While the monocyte and T cell immune phenotypic profile within the HIV-negative individuals reflected those observed in the combined three groups, a distinct profile related to immune dysfunction, was observed within blood donors and people with HIV. These data suggest that varying exposures to lifestyle and infection-related factors may be associated with specific changes in the innate and adaptive immune system, that all contribute to age advancement.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Monocyte and T Cell Immune Phenotypic Profiles Associated With Age Advancement Differ Between People With HIV, Lifestyle-Comparable Controls and Blood Donors

et al. 2020

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European cohorts of older HIV adults: POPPY, AGEhIV, GEPPO, COBRA and FUNCFRAIL

et al. 2019

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Persistence of monocyte activation under treatment in people followed since acute HIV-1 infection relative to participants at high or low risk of HIV infection

et al. 2020

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Background Interpretation of the increase in certain inflammatory markers in virally suppressed HIV-infected individuals must rely on an appropriate uninfected control group well characterized for non-HIV-related factors that contribute to chronic inflammation, e.g. smoking, alcohol consumption, or being overweight. We compared the inflammatory profiles of HIV-infected participants under long-term antiretroviral therapy (ART) with those of two HIV-uninfected groups with contrasting health behaviours. Methods We studied 150 HIV-infected participants (42 women, 108 men) under long-term ART (median, 6 years) followed in the ANRS PRIMO cohort since acute/early HIV-1 infection (AHI) diagnosis. Sex and age-matched controls were sampled from i) the ANRS IPERGAY pre-exposure prophylaxis trial among men at high risk for HIV infection and with high frequencies of non-HIV factors of inflammation ii) the ANRS COHVAC cohort of volunteers in vaccine trials with a low-risk profile for HIV infection . We measured the plasma levels of ten inflammatory markers. Findings After adjusting for smoking, alcohol use and body mass index, both HIV-infected men and women had higher levels of sCD14, sCD163, sTNFRII and I-FABP than their high-risk IPERGAY and low-risk COHVAC counterparts. Hierarchical clustering showed a subset of 15 PRIMO participants to have an inflammatory profile similar to that of most HIV-negative participants. These participants already had favourable markers at AHI diagnosis. Interpretation Long-term ART, even when initiated at a low level of immunodeficiency, fails to normalize monocyte/macrophage activation and gut epithelial dysfunction. Persistent inflammation under treatment may be related to an increased inflammatory profile since AHI. Funding ANRS and Paris-Saclay University.

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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

Cited by 18 publications

References 56 publications

Monocyte and T Cell Immune Phenotypic Profiles Associated With Age Advancement Differ Between People With HIV, Lifestyle-Comparable Controls and Blood Donors

Monocyte and T Cell Immune Phenotypic Profiles Associated With Age Advancement Differ Between People With HIV, Lifestyle-Comparable Controls and Blood Donors

European cohorts of older HIV adults: POPPY, AGEhIV, GEPPO, COBRA and FUNCFRAIL

Persistence of monocyte activation under treatment in people followed since acute HIV-1 infection relative to participants at high or low risk of HIV infection

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