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Journal article
The Effect of Chloroquine on Immune Activation and Interferon Signatures Associated with HIV-1
AIDS research and human retroviruses, v 32(7), pp 636-647
Jul 2016
PMID: 26935044
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- The Effect of Chloroquine on Immune Activation and Interferon Signatures Associated with HIV-1
- Creators
- Jeffrey M Jacobson - Drexel UniversitySteven E Bosinger - Emory UniversityMinhee Kang - Harvard UniversityPablo Belaunzaran-Zamudio - Johns Hopkins UniversityRoy M Matining - Harvard UniversityCara C Wilson - University of Colorado DenverCharles Flexner - Johns Hopkins MedicineBrian Clagett - Case Western Reserve UniversityJill Plants - Rush UniversitySarah Read - Office of AIDS ResearchLynette Purdue - Office of AIDS ResearchLaurie Myers - Frontier Science & Technology Research FoundationLinda Boone - Social and Scientific Systems (United States)Pablo Tebas - University of PennsylvaniaPrincy Kumar - Georgetown UniversityDavid Clifford - Washington University in St. LouisDaniel Douek - Vaccine Research CenterGuido Silvestri - Emory UniversityAlan L Landay - Rush UniversityMichael M Lederman - Case Western Reserve UniversityAIDS Clinical Trial Grp A5258 Prot
- Publication Details
- AIDS research and human retroviruses, v 32(7), pp 636-647
- Publisher
- Mary Ann Liebert
- Grant note
- UM1 AI106701 / NIAID NIH HHS UM1 AI069501 / NIAID NIH HHS UM1 AI069423 / NIAID NIH HHS UM1 AI069494 / NIAID NIH HHS UL1 TR000457 / NCATS NIH HHS UL1 TR001111 / NCATS NIH HHS UM1 AI069465 / NIAID NIH HHS UM1 AI068636 / NIAID NIH HHS UL1 TR001082 / NCATS NIH HHS UM1 AI069534 / NIAID NIH HHS P30 AI050410 / NIAID NIH HHS P30 AI045008 / NIAID NIH HHS UM1 AI069452 / NIAID NIH HHS P51 OD011132 / NIH HHS UM1 AI069412 / NIAID NIH HHS UM1 AI069419 / NIAID NIH HHS UM1 AI068634 / NIAID NIH HHS UM1 AI069439 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:000379609100003
- Scopus ID
- 2-s2.0-84976485600
- Other Identifier
- 991019335244204721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Immunology
- Infectious Diseases
- Virology