title: The Effect of Chloroquine on Immune Activation and Interferon Signatures Associated with HIV-1.
abstract: Immune activation associated with HIV-1 infection contributes to morbidity and mortality. We studied whether chloroquine, through Toll-like receptor (TLR) antagonist properties, could reduce immune activation thought to be driven by TLR ligands, such as gut-derived bacterial elements and HIV-1 RNAs. AIDS Clinical Trials Group A5258 was a randomized, double-blind, placebo-controlled study in 33 HIV-1-infected participants off antiretroviral therapy (ART) and 37 participants on ART. Study participants in each cohort were randomized 1:1 to receive chloroquine 250 mg orally for the first 12 weeks then cross over to placebo for 12 weeks or placebo first and then chloroquine. Combining the periods of chloroquine use in both arms of the on-ART cohort yielded a modest reduction in the proportions of CD8 T cells co-expressing CD38 and DR (median decrease = 3.0%, p = .003). The effect on immune activation in the off-ART cohort was likely confounded by increased plasma HIV-1 RNA during chloroquine administration (median 0.29 log10 increase, p < .001). Transcriptional analyses in the off-ART cohort showed decreased expression of interferon-stimulated genes in 5 of 10 chloroquine-treated participants and modest decreases in CD38 and CCR5 RNAs in all chloroquine-treated participants. Chloroquine modestly reduced immune activation in ART-treated HIV-infected participants. Clinical Trials Registry Number: NCT00819390.
authors.affiliation: 1 Drexel University College of Medicine , Philadelphia, Pennsylvania.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Jacobson
authors.affiliation: 2 Emory University , Atlanta, Georgia .
authors.forename: Steven E
authors.initials: SE
authors.lastname: Bosinger
authors.affiliation: 3 Harvard University School of Public Health , Boston, Massachusetts.
authors.forename: Minhee
authors.initials: M
authors.lastname: Kang
authors.affiliation: 4 Johns Hopkins University School of Public Health , Baltimore, Maryland.
authors.forename: Pablo
authors.initials: P
authors.lastname: Belaunzaran-Zamudio
authors.affiliation: 3 Harvard University School of Public Health , Boston, Massachusetts.
authors.forename: Roy M
authors.initials: RM
authors.lastname: Matining
authors.affiliation: 5 University of Colorado , Denver, Colorado.
authors.forename: Cara C
authors.initials: CC
authors.lastname: Wilson
authors.affiliation: 6 Johns Hopkins University School of Medicine , Baltimore, Maryland.
authors.forename: Charles
authors.initials: C
authors.lastname: Flexner
authors.affiliation: 7 Case Western Reserve University , Cleveland, Ohio.
authors.forename: Brian
authors.initials: B
authors.lastname: Clagett
authors.affiliation: 8 Rush University School of Medicine , Chicago, Illinois.
authors.forename: Jill
authors.initials: J
authors.lastname: Plants
authors.affiliation: 9 Division of AIDS , NIAID, Bethesda, Maryland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Read
authors.affiliation: 9 Division of AIDS , NIAID, Bethesda, Maryland.
authors.forename: Lynette
authors.initials: L
authors.lastname: Purdue
authors.affiliation: 10 Frontier Science , Amherst, New York.
authors.forename: Laurie
authors.initials: L
authors.lastname: Myers
authors.affiliation: 11 Social and Scientific Systems, Inc., Silver Springs, Maryland.
authors.forename: Linda
authors.initials: L
authors.lastname: Boone
authors.affiliation: 12 University of Pennsylvania School of Medicine , Philadelphia, Pennsylvania.
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.affiliation: 13 Georgetown University Medical School , Washington, District of Columbia.
authors.forename: Princy
authors.initials: P
authors.lastname: Kumar
authors.affiliation: 14 Washington University School of Medicine , St. Louis, Missouri.
authors.forename: David
authors.initials: D
authors.lastname: Clifford
authors.affiliation: 15 Vaccine Research Center , NIAID, Bethesda, Maryland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Douek
authors.affiliation: 2 Emory University , Atlanta, Georgia .
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.affiliation: 8 Rush University School of Medicine , Chicago, Illinois.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Landay
authors.affiliation: 7 Case Western Reserve University , Cleveland, Ohio.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002738:Chloroquine / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D056724:Immunity, Humoral / Q000187:drug effects*; D007155:Immunologic Factors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D007155:Immunologic Factors; D010919:Placebos; D002738:Chloroquine