The Effect of Chloroquine on Immune Activation and Interferon Signatures Associated with HIV-1

Jeffrey M. Jacobson, Steven E. Bosinger, Minhee Kang, Pablo Belaunzaran-Zamudio, Roy M. Matining, Cara C. Wilson, Charles Flexner, Brian Clagett, Jill Plants, Sarah Read, Lynette Purdue, Laurie Myers, Linda Boone, Pablo Tebas, Princy Kumar, David Clifford, Daniel Douek, Guido Silvestri, Alan L. Landay, Michael M. Lederman

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)636-647
Number of pages12
JournalAIDS research and human retroviruses
Volume32
Issue number7
DOIs
StatePublished - Jul 1 2016

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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  • Cite this

    Jacobson, J. M., Bosinger, S. E., Kang, M., Belaunzaran-Zamudio, P., Matining, R. M., Wilson, C. C., Flexner, C., Clagett, B., Plants, J., Read, S., Purdue, L., Myers, L., Boone, L., Tebas, P., Kumar, P., Clifford, D., Douek, D., Silvestri, G., Landay, A. L., & Lederman, M. M. (2016). The Effect of Chloroquine on Immune Activation and Interferon Signatures Associated with HIV-1. AIDS research and human retroviruses, 32(7), 636-647. https://doi.org/10.1089/aid.2015.0336