Effects of Hydroxychloroquine on Immune Activation and Disease Progression Among HIV-Infected Patients Not Receiving Antiretroviral Therapy A Randomized Controlled Trial

被引：126

作者：

Paton, Nicholas I. ^{[1
]}

Goodall, Ruth L. ^{[1
]}

Dunn, David T. ^{[1
]}

Franzen, Samuel ^{[2
]}

Collaco-Moraes, Yolanda ^{[1
]}

Gazzard, Brian G. ^{[3
]}

Williams, Ian G. ^{[4
]}

Fisher, Martin J. ^{[5
]}

Winston, Alan ^{[6
]}

Fox, Julie ^{[7
]}

Orkin, Chloe ^{[8
]}

Herieka, Elbushra A. ^{[9
]}

Ainsworth, Jonathan G. ^{[10
]}

Post, Frank A. ^{[11
,12
]}

Wansbrough-Jones, Mark ^{[13
]}

Kelleher, Peter ^{[2
,3
]}

机构：

[1] MRC Clin Trials Unit, London WC2B 6NH, England

[2] Univ London Imperial Coll Sci Technol & Med, Chelsea & Westminster Hosp, Immunol Sect, London SW7 2AZ, England

[3] Chelsea & Westminster NHS Fdn, NHS Trust, London, England

[4] Mortimer Market Ctr, London, England

[5] Brighton & Sussex Univ Hosp, NHS Trust, Brighton, E Sussex, England

[6] St Marys Hosp, London, England

[7] St Thomas Hosp, London, England

[8] Barts & London NHS Trust, London, England

[9] Royal Bournemouth Hosp, Bournemouth, Dorset, England

[10] N Middlesex Univ Hosp, London, England

[11] Kings Coll Hosp London, London, England

[12] Kings Coll London, London, England

[13] St George Hosp, London, England

来源：

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION | 2012年 / 308卷 / 04期

基金：

英国惠康基金;

关键词：

T-CELL-ACTIVATION; LYMPHOCYTE-ACTIVATION; INHIBITION; CHLOROQUINE; REPLICATION; INFECTIVITY; DIDANOSINE; MECHANISM; APOPTOSIS; MARKERS;

D O I：

10.1001/jama.2012.6936

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Context Therapies to decrease immune activation might be of benefit in slowing HIV disease progression. Objective To determine whether hydroxychloroquine decreases immune activation and slows CD4 cell decline. Design, Setting, and Patients Randomized, double-blind, placebo-controlled trial performed at 10 HIV outpatient clinics in the United Kingdom between June 2008 and February 2011. The 83 patients enrolled had asymptomatic HIV infection, were not taking antiretroviral therapy, and had CD4 cell counts greater than 400 cells/mu L. Intervention Hydroxychloroquine, 400 mg, or matching placebo once daily for 48 weeks. Main Outcome Measures The primary outcome measure was change in the proportion of activated CD8 cells (measured by the expression of CD38 and HLA-DR surface markers), with CD4 cell count and HIV viral load as secondary outcomes. Analysis was by intention to treat using mixed linear models. Results There was no significant difference in CD8 cell activation between the 2 groups (-4.8% and -4.2% in the hydroxychloroquine and placebo groups, respectively, at week 48; difference, -0.6%; 95% CI, -4.8% to 3.6%; P = .80). Decline in CD4 cell count was greater in the hydroxychloroquine than placebo group (-85 cells/mu L vs -23 cells/mu L at week 48; difference, -62 cells/mu L; 95% CI, -115 to -8; P = .03). Viral load increased in the hydroxychloroquine group compared with placebo (0.61 log(10) copies/mL vs 0.23 log(10) copies/mL at week 48; difference, 0.38 log(10) copies/mL; 95% CI, 0.13 to 0.63; P = .003). Antiretroviral therapy was started in 9 patients in the hydroxychloroquine group and 1 in the placebo group. Trial medication was well tolerated, but more patients reported influenza-like illness in the hydroxychloroquine group compared with the placebo group (29% vs 10%; P = .03). Conclusion Among HIV-infected patients not taking antiretroviral therapy, the use of hydroxychloroquine compared with placebo did not reduce CD8 cell activation but did result in a greater decline in CD4 cell count and increased viral replication.

引用

页码：353 / 361

页数：9

共 34 条

[21] Reduction of Immune Activation with Chloroquine Therapy during Chronic HIV Infection [J].