Altered Monocyte Phenotype in HIV-1 Infection Tends to Normalize with Integrase-Inhibitor-Based Antiretroviral Therapy.

TitleAltered Monocyte Phenotype in HIV-1 Infection Tends to Normalize with Integrase-Inhibitor-Based Antiretroviral Therapy.
Publication TypeJournal Article
Year of Publication2015
AuthorsMcCausland MR, Juchnowski SM, Zidar DA, Kuritzkes DR, Andrade A, Sieg SF, Lederman MM, Funderburg NT
JournalPLoS One
Volume10
Issue10
Paginatione0139474
Date Published2015
ISSN1932-6203
KeywordsAdult, Anti-HIV Agents, Antigens, CD, Antiretroviral Therapy, Highly Active, Cell Separation, Drug Combinations, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination, Female, Flow Cytometry, HIV Infections, HIV Integrase Inhibitors, HIV-1, HLA-DR Antigens, Humans, Immunophenotyping, Male, Middle Aged, Monocytes, Raltegravir Potassium, Receptors, CCR2, Receptors, Chemokine, Viral Load, Viremia
Abstract

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.

DOI10.1371/journal.pone.0139474
Alternate JournalPLoS ONE
PubMed ID26430882
PubMed Central IDPMC4591977
Grant ListAI 68636 / AI / NIAID NIH HHS / United States
AI36219 / AI / NIAID NIH HHS / United States
R00 HL108743 / HL / NHLBI NIH HHS / United States
R56 HL126563 / HL / NHLBI NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States