JAMA：羟氯喹不会减缓病人HIV的疾病发展

伦敦医学研究委员会临床试验单位的Nicholas I. Paton, M.D., F.R.C.P.及其同事开展了一项研究，旨在检查羟氯喹是否可降低免疫激活及炎症并随之减缓HIV早期疾病的进展。羟氯喹是一种具有免疫调节和抗炎性质的药物；有报告显示，它在体外具有抗HIV的性质。相关成果刊登在了JAMA上。

根据文章的背景资料：“国际性的HIV治疗方针建议，抗逆转录病毒治疗应该在CD4 细胞计数达到350个细胞/微升时开始使用，但资源的限制阻止了这一建议在许多国家中的实施。一种可减缓CD4 细胞下降速度的廉价、安全且耐受良好的干预方法（并因而延迟开始抗逆转录病毒组合疗法的时间）因此会变得有吸引力。”

该随机化、有安慰剂作为对照的试验是在2008年6月至2011年2月间在英国的10个HIV门诊部门开展的。所接纳的83名患者为无症状性HIV感染患者，他们没有接受抗逆转录病毒的治疗，其CD4 细胞计数大于400个细胞/微升。患者每日服用400毫克的羟氯喹或是与其相匹配的安慰剂达48周。

研究人员发现“在那些没有接受抗逆转录病毒疗法的HIV慢性感染的病人中，羟氯喹不会降低免疫激活但会对CD4细胞计数产生有害的影响并会增加HIV的病毒复制。需要有替代性的干预手段来减少HIV早期感染中的免疫激活和疾病进展。”

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Effects of hydroxychloroquine on immune activation in ART- naïve patients: a 48-week randomised, double-blind, placebo-controlled trial

N. Paton, HCQ-01 Trial Group

Background: HIV-induced immune activation and inflammation are thought to play an important role in disease pathogenesis. We hypothesised that hydroxychloroquine (HCQ), a long-established and safe anti-inflammatory and immunomodulatory drug might be of benefit. Methods: We performed a prospective, randomised, double-blind, placebo controlled trial in asymptomatic, ART-naive HIV-infected patients with a CD4 count above 400 cells/mm3. Patients were randomised to receive HCQ 400mg or placebo once daily for 48 weeks. The primary endpoint was change in immune activation from baseline to week 48, measured by the proportion of CD8 T-cells expressing CD38+ and HLA-DR+ (CD8CD38DR+). Results: We randomised 83 patients (41 placebo, 42 HCQ); 93% male, 88% white; median baseline CD4 count 492 cells/mm3, VL 4.2 log10 copies/ml, and CD8CD38DR+ 23%. There was no difference between the groups in change from baseline in CD8CD38DR+, IL-6 or D-dimer, but the HCQ group showed a trend towards higher VL and more rapid loss of CD4 cells (see table). In the HCQ group 16 patients discontinued treatment (9 started ART, 1 SAE, 6 patient decision), and in the placebo group 7 discontinued treatment (1 started ART, 1 SAE, 2 AE, 3 patient decision).