Moderate to severe HIV-associated neurocognitive impairment A randomized placebo-controlled trial of lithium
Moderate to severe HIV-associated neurocognitive impairment A randomized placebo-controlled trial of lithium
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DOI：
10.1097/md.0000000000005401
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发表时间：
2016-11-01
期刊：
影响因子：
1.6
通讯作者：
Joska, John A.
中科院分区：
文献类型：
--
作者：
Decloedt, Eric H.;Freeman, Carla;Joska, John A.
背景：尽管抗逆转录病毒治疗（ART）有效，但 HIV 相关神经认知障碍（HAND）仍然非常普遍。一些 HAND 辅助药物疗法的研究结果令人失望，但初步数据表明锂可能会带来临床益处。此外，锂的低成本将有助于艾滋病毒负担最重的低收入和中等收入国家获得锂。方法：我们的目标是评估锂对中度至重度手足口病患者的 24 周疗效和安全性。我们的主要疗效终点是总体赤字评分 (GDS) 从基线到 24 周的变化，而我们的次要终点是质子磁共振波谱 (H-1-MRS) 脑代谢物浓度的变化。我们进行了一项为期 24 周的随机安慰剂对照试验，将锂作为辅助药物治疗。我们招募了患有中度至重度手足口病的参与者，接受了至少 6 个月的 ART 治疗，病毒载量受到抑制，并前往南非开普敦的公共部门初级保健诊所就诊。我们将 66 名参与者随机分配到锂剂组 (n = 32) 或安慰剂组 (n = 34)。每 12 小时服用一次锂或安慰剂，并滴定以达到 0.6 至 1.0mmol/L 的维持目标血浆浓度。为接受安慰剂的参与者生成假锂浓度。结果：共有 61 名参与者完成了研究（锂组 = 30；安慰剂组 = 31）。入组参与者的平均年龄为 40 岁，CD4+ T 细胞计数中位数为 500 个细胞/mL。锂剂组和安慰剂组在基线和第 24 周之间的 GDS 中位变化分别为 -0.57（95% 置信区间 [CI] -0.77，-0.32）和 -0.56（-0.69，-0.34），平均差为 -0.054（95% CI -0.26，0.15）； P = 0.716。根据年龄、损伤严重程度、CD4+ 计数、ART 时间和 ART 方案进行分析时，改善情况仍然相似。治疗组之间的标准 H-1-MRS 代谢物浓度相似。该研究药物在两个研究组中均具有良好的耐受性。发生了 6 例严重不良事件，但没有一例被认为与研究药物有关。结论：使用 HAND 进行 ART 的患者辅助锂药物治疗耐受性良好，但对神经认知障碍没有额外益处。
Background: HIV-associated neurocognitive disorder (HAND) remains highly prevalent despite effective anti-retroviral therapy (ART). A number of adjunctive pharmacotherapies for HAND have been studied with disappointing results, but preliminary data suggest that lithium may provide clinical benefit. In addition, the low cost of lithium would facilitate access in low- and middle-income countries which carry the greatest burden of HIV.Methods: Our objective was to evaluate the 24-week efficacy and safety of lithium in patients with moderate to severe HAND. Our primary efficacy endpoint was the change in Global Deficit Score (GDS) from baseline to 24 weeks, whereas our secondary endpoint was the change in proton magnetic resonance spectroscopy (H-1-MRS) brain metabolite concentrations. We conducted a 24-week randomized placebo-controlled trial of lithium as adjunctive pharmacotherapy. We enrolled participants with moderate to severe HAND, on ART for at least 6 months, with suppressed viral loads and attending public sector primary care clinics in Cape Town, South Africa. We randomized 66 participants to lithium (n = 32) or placebo (n = 34). Lithium or placebo was dosed 12-hourly and titrated to achieve the maintenance target plasma concentration of 0.6 to 1.0mmol/L. Sham lithium concentrations were generated for participants receiving placebo.Results: Totally 61 participants completed the study (lithium arm = 30; placebo arm = 31). Participants at enrolment had a mean age of 40 years and a median CD4+ T-cell count of 500cells/mL. The median change in GDS between baseline and week 24 for the lithium and placebo arms were -0.57 (95% confidence interval [CI] -0.77, -0.32) and -0.56 (-0.69, -0.34) respectively, with a mean difference of -0.054 (95% CI -0.26, 0.15); P = 0.716. The improvement remained similar when analyzed according to age, severity of impairment, CD4+ count, time on ART, and ART regimen. Standard H-1-MRS metabolite concentrations were similar between the treatment arms. The study drug was well tolerated in both study arms. Six serious adverse events occurred, but none were considered related to the study drug.Conclusion: Adjunctive lithium pharmacotherapy in patients on ART with HAND was well tolerated but had no additional benefit on neurocognitive impairment.