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Effects of hydroxychloroquine on immune activation and disease progression among HIV-infected patients not receiving antiretroviral therapy: a randomized controlled trial.

ABSTRACT: 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/?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/?L vs -23 cells/?L at week 48; difference, -62 cells/?L; 95% CI, -115 to -8; P = .03). Viral load increased in the hydroxychloroquine group compared with placebo (0.61 log10 copies/mL vs 0.23 log10 copies/mL at week 48; difference, 0.38 log10 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. TRIAL REGISTRATION:isrctn.org Identifier: ISRCTN30019040.

SUBMITTER: Paton NI

PROVIDER: S-EPMC3821003 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Effects of hydroxychloroquine on immune activation and disease progression among HIV-infected patients not receiving antiretroviral therapy: a randomized controlled trial.

Paton Nicholas I NI Goodall Ruth L RL Dunn David T DT Franzen Samuel S Collaco-Moraes Yolanda Y Gazzard Brian G BG Williams Ian G IG Fisher Martin J MJ Winston Alan A Fox Julie J Orkin Chloe C Herieka Elbushra A EA Ainsworth Jonathan G JG Post Frank A FA Wansbrough-Jones Mark M Kelleher Peter P

JAMA 20120701 4

<h4>Context</h4>Therapies to decrease immune activation might be of benefit in slowing HIV disease progression.<h4>Objective</h4>To determine whether hydroxychloroquine decreases immune activation and slows CD4 cell decline.<h4>Design, setting, and patients</h4>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 t ...[more]

PMID: 22820788

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Project description:BACKGROUND:Identifying characteristics of HIV-infected adults likely to have poor treatment outcomes can be useful for targeting interventions efficiently. Research in economics and psychology suggests that individuals' intertemporal time preferences, which indicate the extent to which they trade-off immediate vs. future cost and benefits, can influence various health behaviors. While there is empirical support for the association between time preferences and various non-HIV health behaviors and outcomes, the extent to which time preferences predict outcomes of those receiving antiretroviral therapy (ART) has not been examined previously. METHODS:HIV-infected adults initiating ART were enrolled at a health facility in Kenya. Participants' time preferences were measured at enrollment and used to classify them as having either a low or high discount rate for future benefits. At 48 weeks, we assessed mortality and ART adherence, as measured by Medication Event Monitoring System (MEMS). Logistic regression models adjusting for socio-economic characteristics and risk factors were used to determine the association between time preferences and mortality as well as MEMS adherence ?90%. RESULTS:Overall, 44% (96/220) of participants were classified as having high discount rates. Participants with high discount rates had significantly higher 48-week mortality than participants with low discount rates (9.3% vs. 3.1%; adjusted odds ratio 3.84; 95% CI 1.03, 14.50). MEMS adherence ?90% was similar for participants with high vs. low discount rates (42.3% vs. 49.6%, AOR 0.70; 95% CI 0.40, 1.25). CONCLUSION:High discount rates were associated with significantly higher risk of mortality among HIV-infected patients initiating ART. Greater use of time preference measures may improve identification of patients at risk of poor clinical outcomes. More research is needed to further identify mechanisms of action and also to build upon and test the generalizability of this finding.

Project description:BACKGROUND:The aim was to determine the association between bone health and inflammation, T-cell activation, and monocyte activation among HIV-infected persons on stable antiretroviral therapy. METHODS:We performed a cross-sectional analysis of all the subjects enrolling in the Stopping Atherosclerosis and Treating Unhealthy bone with RosuvastatiN in HIV trial with available skeletal assessments by dual-energy x-ray absorptiometry, inflammation, and immune activation markers. Analyses used were Wilcoxon rank-sum tests, Spearman correlation coefficients, and linear regression. RESULTS:One hundred forty-two subjects were included: 78% men, 69% African American, median age 46.3 years, CD4 count 604 cells per microliter, and 77% with undetectable HIV-1 RNA. Twenty-three percent had osteopenia/osteoporosis at the hip, and 21% had this at the lumbar spine. Soluble vascular cell adhesion molecule-1 was correlated with hip (r = -0.22) and spine (r = -0.23) bone mineral density (BMD), and bone turnover markers (r = 0.20-0.33; all P < 0.05). No significant correlations were observed between the BMD and T-cell activation (%CD38HLA-DR on CD4 or CD8 T cells), monocyte activation (CD14CD16, sCD14, and sCD163), or inflammatory markers [interleukin (IL)-6, tumor necrosis factor-?, highly sensitive C-reactive protein, D-dimer, receptor activator of NF-kB ligand, osteoprotegerin, soluble tumor necrosis factor-RI and II]. In regression models including traditional bone risk factors, hip BMD was associated with age, race, and body mass index; spine BMD was associated with race, family history of hip fracture, trunk fat, tenofovir, and HIV RNA; bone resorption (c-terminal collagen crosslinks) was associated with intracellular adhesion molecule-1 and trunk fat; bone formation (P1NP) was associated with soluble vascular cell adhesion molecule-1, trunk and limb fat (P ? 0.05). CONCLUSIONS:Future studies should evaluate the longitudinal association of the adhesion molecules to further elucidate potential contributory mechanisms of bone loss among HIV-infected persons on stable antiretroviral therapy.

Project description:BACKGROUND: Long term use of antiretroviral therapy (ART) in persons living with human immunodeficiency virus (PLWHIV) is associated with disturbances in blood lipids which should be monitored. More data on such disturbances are needed in Cameroon to persuade the country program to institute their routine monitoring. We then sought to determine the prevalence and timing of dyslipidaemia in PLWHIV and receiving ART in a predominantly rural Cameroonian setting. METHODS: A cross-sectional study conducted between August and October 2012 in HIV-infected persons aged 15 years or more and receiving first-line ART for at least six months at The Nkongsamba Regional Hospital in Cameroon. Lipid assays were carried out by enzymatic-linked colorimetric methods. A multiple logistic regression model was used to assess for factors related to dyslipidaemia. RESULTS: Included were 114 participants of whom 83 (72.8%) were females. Their median age was 43 years (IQR: 36-51) and their median CD4 count was 436 cells/?l (IQR: 275-585) after a median duration on ART of 36 months (IQR: 12-60). The prevalence of dyslipidaemia was 70.2%. Hypercholesterolaemia was observed in 34 (29.8%) patients. One-third of them had a high LDL-cholesterol level (LDL-c?130 mg/dl). Hypertriglyceridaemia (TG?150 mg/dl) was present in 59 (51.8%) cases. The proportion of patients with a low HDL-cholesterol (HDL-c<40 mg/dl) was 18.4% while those with a ratio of TC/HDL-c?5 were about 16.7%. A duration of 2-4 years on ART (adjusted Odd Ratio, aOR=5.22, 95% CI: 1.43-19.06, p=0.01), current smokers (aOR=15.94, 95% CI: 1.13-225.61, p=0.04) and a concurrent metabolic disease (aOR=12.54, 95% CI: 1.02-153.86, p=0.48) were independently associated with pro-atherogenic LDL-c values. Alcohol users had a more friendly LDL-c profile (aOR=0.24, 95% CI: 0.07-0.74, p=0.01). CONCLUSION: The study has demonstrated a high prevalence of dyslipidaemia in HIV-patients receiving first-line ART in a predominantly rural setting of Cameroon. There is a need for the country HIV program to institute laboratory monitoring of blood lipids in patients over two years on first line ART with a focus on smokers.

Dataset Information

Effects of hydroxychloroquine on immune activation and disease progression among HIV-infected patients not receiving antiretroviral therapy: a randomized controlled trial.

Publications

Effects of hydroxychloroquine on immune activation and disease progression among HIV-infected patients not receiving antiretroviral therapy: a randomized controlled trial.

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