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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Hydroxychloroquine drastically reduces immune activation in HIV-infected, antiretroviral therapy-treated immunologic nonresponders
Blood, Volume 118, No. 12, Year 2011
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Description
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. © 2011 by The American Society of Hematology.
Authors & Co-Authors
Piconi, Stefania
Italy, Milan
Ospedale Luigi Sacco - Polo Universitario
Rizzardini, Giuliano
Italy, Milan
Ospedale Luigi Sacco - Polo Universitario
Passerini, Simone
Italy, Milan
Ospedale Luigi Sacco - Polo Universitario
Argenteri, Barbara
Italy, Milan
Ospedale Luigi Sacco - Polo Universitario
Meraviglia, Paola
Italy, Milan
Ospedale Luigi Sacco - Polo Universitario
Capetti, Amedeo Ferdinando
Italy, Milan
Ospedale Luigi Sacco - Polo Universitario
Biasin, Mara Raffaella
Italy, Milan
Università Degli Studi Di Milano
Trabattoni, Daria Lucia
Italy, Milan
Università Degli Studi Di Milano
Clerici, Mario S.
Italy, Milan
Università Degli Studi Di Milano
Italy, Milan
Fondazione Don Carlo Gnocchi
Statistics
Citations: 150
Authors: 9
Affiliations: 3
Identifiers
Doi:
10.1182/blood-2011-01-329060
ISSN:
00064971
Research Areas
Infectious Diseases
Study Design
Cohort Study