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Altered Monocyte Phenotype in HIV-1 Infection Tends to Normalize with Integrase-Inhibitor-Based Antiretroviral Therapy.
McCausland, Marie R; Juchnowski, Steven M; Zidar, David A; Kuritzkes, Daniel R; Andrade, Adriana; Sieg, Scott F; Lederman, Michael M; Funderburg, Nicholas T.
Afiliação
  • McCausland MR; Division of Infectious Disease, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
  • Juchnowski SM; Harrington Heart & Vascular Institute, University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
  • Zidar DA; Division of Infectious Disease, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America; Harrington Heart & Vascular Institute, University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
  • Kuritzkes DR; Division of Infectious Diseases, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States of America.
  • Andrade A; Department of Medicine, Division of Infectious Diseases, John Hopkins University, Baltimore, Maryland, United States of America.
  • Sieg SF; Division of Infectious Disease, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
  • Lederman MM; Division of Infectious Disease, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
  • Funderburg NT; School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, Ohio State University, Columbus, Ohio, United States of America.
PLoS One ; 10(10): e0139474, 2015.
Article em En | MEDLINE | ID: mdl-26430882
BACKGROUND: Monocytes are increasingly implicated in the inflammatory consequences of HIV-1 disease, yet their phenotype following antiretroviral therapy (ART) initiation is incompletely defined. Here, we define more completely monocyte phenotype both prior to ART initiation and during 48 weeks of ART. METHODS: Cryopreserved peripheral blood mononuclear cells (PBMCs) were obtained at baseline (prior to ART initiation) and at weeks 12, 24, and 48 of treatment from 29 patients participating in ACTG clinical trial A5248, an open label study of raltegravir/emtricitibine/tenofovir administration. For comparison, cryopreserved PBMCs were obtained from 15 HIV-1 uninfected donors, each of whom had at least two cardiovascular risk factors. Thawed samples were stained for monocyte subset markers (CD14 and CD16), HLA-DR, CCR2, CX3CR1, CD86, CD83, CD40, CD38, CD36, CD13, and CD163 and examined using flow cytometry. RESULTS: In untreated HIV-1 infection there were perturbations in monocyte subset phenotypes, chiefly a higher frequency and density (mean fluorescence intensity-MFI) of HLA-DR (%-p = 0.004, MFI-p = .0005) and CD86 (%-p = 0.012, MFI-p = 0.005) expression and lower frequency of CCR2 (p = 0.0002) expression on all monocytes, lower CCR2 density on inflammatory monocytes (p = 0.045) when compared to the expression and density of these markers in controls' monocytes. We also report lower expression of CX3CR1 (p = 0.014) on patrolling monocytes at baseline, compared to levels seen in controls. After ART, these perturbations tended to improve, with decreasing expression and density of HLA-DR and CD86, increasing CCR2 density on inflammatory monocytes, and increasing expression and density of CX3CR1 on patrolling monocytes. CONCLUSIONS: In HIV-1 infected patients, ART appears to attenuate the high levels of activation (HLA-DR, CD86) and to increase expression of the chemokine receptors CCR2 and CX3CR1 on monocyte populations. Circulating monocyte phenotypes are altered in untreated infection and tend to normalize with ART; the role of these cells in the inflammatory environment of HIV-1 infection warrants further study.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Viremia / Monócitos / Infecções por HIV / HIV-1 / Inibidores de Integrase de HIV Tipo de estudo: Clinical_trials / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Viremia / Monócitos / Infecções por HIV / HIV-1 / Inibidores de Integrase de HIV Tipo de estudo: Clinical_trials / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos