title: Differential levels of soluble inflammatory markers by human immunodeficiency virus controller status and demographics.
abstract: Background.  Human immunodeficiency virus (HIV)-1 elite controllers (ECs) represent an ideal population to study the effects of HIV persistence on chronic inflammation in the absence of antiretroviral therapy (ART). Methods.  Twenty inflammatory markers measured in cohorts of ECs, HIV suppressed noncontrollers, and HIV-uninfected controls were compared using rank-based tests and partial least squares discriminant analysis (PLSDA). Spearman correlations were determined among the inflammatory markers, residual viremia by the single-copy assay, and CD4(+) T cell slope. Results.  Significant differences were seen between cohorts in 15 of the soluble inflammatory markers. Human immunodeficiency virus-1 ECs were found to have the highest levels for all of the markers with the exception of RANTES. In particular, median levels of 7 inflammatory markers (soluble CD14 [sCD14], interferon [IFN]-γ, IFN-γ-inducible protein [IP]-10, interleukin [IL]-4, IL-10, sCD40L, and granulocyte-macrophage colony-stimulating factor) were twice as high in the HIV-1 ECs compared with either of the HIV-suppressed or uninfected groups. Multivariate PLSDA analysis of inflammatory markers improved differentiation between the patient cohorts, discerning gender differences in inflammatory profile amongst individuals on suppressive ART. Soluble markers of inflammation in ECs were not associated with either levels of residual HIV-1 viremia or CD4(+) T cell decline. Conclusions.  Despite maintaining relatively low levels of viremia, HIV-1 ECs had elevated levels of a set of key inflammatory markers. Additional studies are needed to determine whether ECs may benefit from ART and to further evaluate the observed gender differences.
authors.affiliation: Brigham and Women's Hospital , Harvard Medical School , Cambridge, Massachusetts.
authors.forename: Jonathan Z
authors.initials: JZ
authors.lastname: Li
authors.affiliation: Massachusetts Institute of Technology , Cambridge.
authors.forename: Kelly B
authors.initials: KB
authors.lastname: Arnold
authors.affiliation: Massachusetts General Hospital , Boston.
authors.forename: Janet
authors.initials: J
authors.lastname: Lo
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard , Cambridge, Massachusetts.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Dugast
authors.affiliation: Rush University Medical Center , Chicago, Illinois.
authors.forename: Jill
authors.initials: J
authors.lastname: Plants
authors.affiliation: Harvard School of Public Health , Boston, Massachusetts.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ribaudo
authors.affiliation: Massachusetts General Hospital , Boston.
authors.forename: Kevin
authors.initials: K
authors.lastname: Cesa
authors.affiliation: Brigham and Women's Hospital , Harvard Medical School , Cambridge, Massachusetts.
authors.forename: Andrea
authors.initials: A
authors.lastname: Heisey
authors.affiliation: Brigham and Women's Hospital , Harvard Medical School , Cambridge, Massachusetts.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
authors.affiliation: Massachusetts Institute of Technology , Cambridge.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Lauffenburger
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard , Cambridge, Massachusetts.
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
authors.affiliation: Rush University Medical Center , Chicago, Illinois.
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
authors.affiliation: Massachusetts General Hospital , Boston.
authors.forename: Steven
authors.initials: S
authors.lastname: Grinspoon
authors.affiliation: Brigham and Women's Hospital , Harvard Medical School , Cambridge, Massachusetts ; Massachusetts General Hospital , Boston.
authors.forename: Florencia
authors.initials: F
authors.lastname: Pereyra
keywords: HIV elite controllers; antiretroviral therapy; gender; inflammation; low-level viremia