title: Non-classical monocytes predict progression of carotid artery bifurcation intima-media thickness in HIV-infected individuals on stable antiretroviral therapy.
abstract: Inflammation may contribute to cardiovascular disease (CVD) among antiretrovirally suppressed HIV-infected individuals. We assessed relationships of monocyte, CD8 T-cell activation and plasma biomarkers to changes in carotid artery intima-media thickness (CIMT).
  
  
  
  Longitudinal study of HIV-infected subjects ≥40 years and on stable antiretroviral therapy (ART) ≥3 months. Peripheral blood mononuclear cells were immunophenotyped by multiparameteric flow cytometry to quantify classical (CD14(++)CD16(-)), intermediate (CD14(++)CD16(+)), non-classical (CD14(low/+)CD16(++)) and transitional (CD14(+)CD16(-)) monocyte subsets and activated (CD38(+)HLA-DR(+)) CD8(+) T-cells at baseline. Plasma biomarkers were assessed by multiplex Luminex assay. High-resolution B-mode ultrasounds of right carotid arteries were obtained. Changes in CIMT over two years at the right common carotid artery (CIMTCCA) and right bifurcation (CIMTBIF) were outcome variables.
  
  
  
  We studied 50 subjects: 84% male, median age 49 (Q1, Q3; 46, 56) years, median CD4 count 461 (317, 578) cells/mm(3), and with HIV RNA ≤ 50 copies/mL in 84%. Change in CIMTBIF correlated with log values of baseline absolute count of non-classical monocytes (r = 0.37, p = 0.020), and with MCP-1 (r = 0.42, p = 0.0024) and TNF-α (r = 0.30, p = 0.036) levels. In multivariable linear regression, only non-classical monocytes and MCP-1 predicted the change in CIMTBIF, independent of Framingham Risk Score and baseline CIMTBIF. No correlation was noted between CD8 T-cell activation and CIMTBIF change. Monocyte subsets, CD8 T-cell activation, and biomarker concentrations were not correlated with changes in CIMTCCA.
  
  
  
  Our findings highlight the role of non-classical monocytes and MCP-1 in the progression of CIMTBIF in HIV-infected individuals on stable ART independent of traditional cardio-metabolic risk factors.
authors.affiliation: a Hawaii Center for AIDS, John A. Burns School of Medicine , University of Hawaii , Honolulu , HI , USA.
authors.forename: Dominic C
authors.initials: DC
authors.lastname: Chow
authors.affiliation: a Hawaii Center for AIDS, John A. Burns School of Medicine , University of Hawaii , Honolulu , HI , USA.
authors.forename: Jamie M
authors.initials: JM
authors.lastname: Kagihara
authors.affiliation: a Hawaii Center for AIDS, John A. Burns School of Medicine , University of Hawaii , Honolulu , HI , USA.
authors.forename: Guangxiang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: a Hawaii Center for AIDS, John A. Burns School of Medicine , University of Hawaii , Honolulu , HI , USA.|b The Queen's Medical Center , Honolulu , HI , USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Souza
authors.affiliation: c University of Southern California Atherosclerosis Research Unit , CA , USA.
authors.forename: Howard N
authors.initials: HN
authors.lastname: Hodis
authors.affiliation: c University of Southern California Atherosclerosis Research Unit , CA , USA.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Hawaii Center for AIDS, John A. Burns School of Medicine , University of Hawaii , Honolulu , HI , USA.
authors.forename: Brooks I
authors.initials: BI
authors.lastname: Mitchell
authors.affiliation: a Hawaii Center for AIDS, John A. Burns School of Medicine , University of Hawaii , Honolulu , HI , USA.|d Straub Medical Center , Honolulu , HI , USA.
authors.forename: Beau K
authors.initials: BK
authors.lastname: Nakamoto
authors.affiliation: a Hawaii Center for AIDS, John A. Burns School of Medicine , University of Hawaii , Honolulu , HI , USA.
authors.forename: Kalpana J
authors.initials: KJ
authors.lastname: Kallianpur
authors.affiliation: e Blood Systems Research Institute , San Francisco , CA , USA.|f Department of Laboratory Medicine , University of California , San Francisco , CA , USA.
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Keating
authors.affiliation: e Blood Systems Research Institute , San Francisco , CA , USA.|f Department of Laboratory Medicine , University of California , San Francisco , CA , USA.|g Department of Medicine , University of California , San Francisco , CA , USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Norris
authors.affiliation: a Hawaii Center for AIDS, John A. Burns School of Medicine , University of Hawaii , Honolulu , HI , USA.
authors.forename: Lindsay B
authors.initials: LB
authors.lastname: Kohorn
authors.affiliation: a Hawaii Center for AIDS, John A. Burns School of Medicine , University of Hawaii , Honolulu , HI , USA.
authors.forename: Lishomwa C
authors.initials: LC
authors.lastname: Ndhlovu
authors.affiliation: a Hawaii Center for AIDS, John A. Burns School of Medicine , University of Hawaii , Honolulu , HI , USA.
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Shikuma
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000175:diagnosis* / Q000209:etiology*; D059168:Carotid Intima-Media Thickness; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype; D011379:Prognosis
chemical_list: D015415:Biomarkers
keywords: Biomarkers; CIMT; HIV; Monocytes