Hydroxychloroquine drastically reduces immune activation in HIV-infected, antiretroviral therapy-treated immunologic nonresponders

Stefania Piconi, Serena Parisotto, Giuliano Rizzardini, Simone Passerini, Roberta Terzi, Barbara Argenteri, Paola Meraviglia, Amedeo Capetti, Mara Biasin, Daria Trabattoni, Mario Clerici

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Despite optimal suppression of HIV replication, restoration of CD4 + T cells is not always achieved in antiretroviral therapy - treated individuals. Defective CD4 recovery in immunologic nonresponders is possibly associated with TLR-mediated immune activation driven by alterations of gut permeability. Hydroxychloroquine (HCQ) reduces endosomal TLR signaling; thus, we verified whether HCQ could dampen immune activation and be associated with an increase in CD4 + T cells. To this end, we enrolled in a prospective study 20 HIV-infected immunologic nonresponders (CD4 count <200 cells/mL or CD4 increase <5% in the last 12 months) who received 400 mg/day HCQ for 6 months. HCQ had a notable impact on immune activation as shown by significant modifications of the following parameters: (1) reduced plasma lipopolysaccharide; (2) decreased TLR4-expressing CD14 + cells, TLR4-mediated signal transduction, and mRNA synthesis; (3) reduced percentages of activated CD4 + (CD4 +/Ki67 +) and CD14 + (CD14 +/CD69 +) cells; (4) increased T-regulatory cells (Tregs), naive Tregs, and TLR4- expressing Tregs; (5) augmented plasmacytoid dendritic cells and reduced IFNα- secreting plasmacytoid dendritic cells; and (6) reduced IL-6 and TNFα production. HCQ-induced immune modulation was associated with increased percentages of circulating CD4 + T cells and was mostly retained 2 months after therapy interruption. HCQ reduces lipopolysaccharide/ TLR-mediated immune activation; this compound could be a useful immunomodulant in HIV-infected patients. This study is registered at EutraCT as 2009-012499-28 with study number HLS01/ 2009-1-16-03-2009.

Original languageEnglish
Pages (from-to)3263-3272
Number of pages10
JournalBlood
Volume118
Issue number12
DOIs
Publication statusPublished - Sep 22 2011

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Hydroxychloroquine
Chemical activation
HIV
T-cells
Regulatory T-Lymphocytes
T-Lymphocytes
Dendritic Cells
Lipopolysaccharides
Therapeutics
Signal transduction
CD4 Lymphocyte Count
Restoration
Permeability
Interleukin-6
Signal Transduction
Modulation
Prospective Studies
Plasmas
Recovery
Messenger RNA

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Hydroxychloroquine drastically reduces immune activation in HIV-infected, antiretroviral therapy-treated immunologic nonresponders. / Piconi, Stefania; Parisotto, Serena; Rizzardini, Giuliano; Passerini, Simone; Terzi, Roberta; Argenteri, Barbara; Meraviglia, Paola; Capetti, Amedeo; Biasin, Mara; Trabattoni, Daria; Clerici, Mario.

In: Blood, Vol. 118, No. 12, 22.09.2011, p. 3263-3272.

Research output: Contribution to journalArticle

Piconi, S, Parisotto, S, Rizzardini, G, Passerini, S, Terzi, R, Argenteri, B, Meraviglia, P, Capetti, A, Biasin, M, Trabattoni, D & Clerici, M 2011, 'Hydroxychloroquine drastically reduces immune activation in HIV-infected, antiretroviral therapy-treated immunologic nonresponders', Blood, vol. 118, no. 12, pp. 3263-3272. https://doi.org/10.1182/blood-2011-01-329060
Piconi, Stefania ; Parisotto, Serena ; Rizzardini, Giuliano ; Passerini, Simone ; Terzi, Roberta ; Argenteri, Barbara ; Meraviglia, Paola ; Capetti, Amedeo ; Biasin, Mara ; Trabattoni, Daria ; Clerici, Mario. / Hydroxychloroquine drastically reduces immune activation in HIV-infected, antiretroviral therapy-treated immunologic nonresponders. In: Blood. 2011 ; Vol. 118, No. 12. pp. 3263-3272.
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