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:OBJECTIVES:We examine long-term retention of adults, adolescents and children on antiretroviral therapy under different HIV treatment guidelines in Malawi. DESIGN:Prospective cohort study. SETTING AND PARTICIPANTS:Adults and children starting ART between 2005 and 2015 in 21 health facilities in southern Malawi. METHODS:We used survival analysis to assess retention at clinic level, Cox regression to examine risk factors for loss to follow up, and competing risk analysis to assess long-term outcomes of people on antiretroviral therapy (ART). RESULTS:We included 132,274 individuals in our analysis, totalling 270,256 person years of follow up (PYFU; median per patient 1.3, interquartile range (IQR) 0.26-3.1), 62% were female and the median age was 32 years. Retention on ART was lower in the first year on ART compared to subsequent years for all guideline periods and age groups. Infants (0-3 years), adolescents and young adults (15-24 years) were at highest risk of LTFU. Comparing the different calendar periods of ART initiation we found that retention improved initially, but remained stable thereafter. CONCLUSION:Even though the number of patients and the burden on health care system increased substantially during the study period of rapid ART expansion, retention on ART improved in the early years of ART provision, but gains in retention were not maintained over 5 years on ART. Reducing high attrition in the first year of ART should remain a priority for ART programs, and so should addressing poor retention among adolescents, young adults and men.
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Project description:Statins, or 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, have anti-inflammatory effects that are independent of their lipid-lowering properties. Despite suppressive antiretroviral therapy (ART), elevated levels of immune activation and inflammation often persist.The Stopping Atherosclerosis and Treating Unhealthy Bone With Rosuvastatin in HIV (SATURN-HIV) trial is a randomized, double-blind, placebo-controlled study, designed to investigate the effects of rosuvastatin (10 mg/daily) on markers of cardiovascular disease risk in ART-treated human immunodeficiency virus (HIV)-infected subjects. A preplanned analysis was to assess changes in markers of immune activation at week 24. Subjects with low-density lipoprotein cholesterol <130 mg/dL and heightened immune activation (%CD8(+)CD38(+)HLA-DR(+) ?19%, or plasma high-sensitivity C-reactive protein ?2 mg/L) were randomized to receive rosuvastatin or placebo. We measured plasma (soluble CD14 and CD163) and cellular markers of monocyte activation (proportions of monocyte subsets and tissue factor expression) and T-cell activation (expression of CD38, HLA-DR, and PD1).After 24 weeks of rosuvastatin, we found significant decreases in plasma levels of soluble CD14 (-13.4% vs 1.2%, P = .002) and in proportions of tissue factor-positive patrolling (CD14(Dim)CD16(+)) monocytes (-38.8% vs -11.9%, P = .04) in rosuvastatin-treated vs placebo-treated subjects. These findings were independent of the lipid-lowering effect and the use of protease inhibitors. Rosuvastatin did not lead to any changes in levels of T-cell activation.Rosuvastatin treatment effectively lowered markers of monocyte activation in HIV-infected subjects on antiretroviral therapy.NCT01218802.
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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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