In:
Blood, American Society of Hematology, Vol. 118, No. 12 ( 2011-09-22), p. 3263-3272
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.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood-2011-01-329060
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2011
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
