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 IFN alpha-secreting plasmacytoid dendritic cells; and (6) reduced IL-6 and TNF alpha 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. (Blood. 2011;118(12):3263-3272)
Hydroxychloroquine drastically reduces immune activation in HIV-infected, antiretroviral therapy-treated immunologic nonresponders / S. Piconi, S. Parisotto, G. Rizzardini, S. Passerini, R. Terzi, B. Argenteri, P. Meraviglia, A. Capetti, M. Biasin, D. Trabattoni, M. Clerici. - In: BLOOD. - ISSN 0006-4971. - 118:12(2011 Sep 22), pp. 3263-3272.
Hydroxychloroquine drastically reduces immune activation in HIV-infected, antiretroviral therapy-treated immunologic nonresponders
S. PiconiPrimo
;S. ParisottoSecondo
;S. Passerini;A. Capetti;M. Biasin;D. TrabattoniPenultimo
;M. ClericiUltimo
2011
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 IFN alpha-secreting plasmacytoid dendritic cells; and (6) reduced IL-6 and TNF alpha 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. (Blood. 2011;118(12):3263-3272)File | Dimensione | Formato | |
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