Monocyte Dysfunction, Activation, and Inflammation After Long-Term Antiretroviral Therapy in an African Cohort.
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ABSTRACT: Background
Monocyte dysfunction may persist during antiretroviral therapy (ART).Methods
Frozen peripheral blood mononuclear cells of 30 human immunodeficiency virus (HIV)-infected ART-treated adults with sustained viral suppression and CD4 counts ≥500 cells/µL were consecutively analyzed for monocyte phenotypes and function.Results
Nonclassical monocytes (CD14+, CD16++), interleukin (IL)-1β production, and expression of CD40 and CD86 were lower among ART-treated HIV-infected adults relative to age-matched HIV-negative adults (P = .01, P = .01, and P = .02, respectively). Intestinal fatty acid-binding protein, IL6, and soluble CD14 were higher among HIV-infected adults relative to HIV-negative adults (P = .0002, P = .04, and P = .0017, respectively).Conclusions
Further investigation is required to understand drivers of persistent monocyte activation and dysfunction.
SUBMITTER: Nabatanzi R
PROVIDER: S-EPMC6761975 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background:We examined changes in soluble inflammatory cytokines and T-cell activation after antiretroviral therapy (ART) initiation in an AIDS Clinical Trials Group (ACTG) nested case-control study. Methods:Cases were 143 human immunodeficiency virus (HIV)-infected adults who developed a non-AIDS event; 315 controls remained event-free. Specimens were tested pre-ART, year 1 post-ART, and at the visit preceding the event. Conditional logistic regression evaluated the associations of biomarker changes with non-AIDS events. Results:Inflammatory and most activation biomarkers declined from pre-ART to year 1 for cases and controls. Subsequently, inflammatory biomarkers remained mostly stable in controls but not cases. Cellular activation markers generally declined for both cases and controls between year 1 and the pre-event sampling. Controls with greater pre-ART RNA levels or lower CD4+ levels had higher biomarker levels while also experiencing greater biomarker declines in the first year of ART. Changes in biomarkers to year 1 showed no significant associations with non-AIDS events. Cases, however, had significantly greater increases in all plasma biomarkers (but not cellular activation) from year 1 to the visit preceding the event. Conclusions:Inflammation increases prior to non-AIDS events in treated HIV-infected adults. These biomarker changes may reflect subclinical disease processes or other alterations in the inflammatory environment that causally contribute to disease. Clinical Trials Registration:NCT00001137.
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