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Adjunctive sertraline for asymptomatic cryptococcal antigenemia: A randomized clinical trial.
Medical Mycology ( IF 2.9 ) Pub Date : 2020-05-16 , DOI: 10.1093/mmy/myaa033
David R Boulware 1 , Elizabeth Nalintya 2 , Radha Rajasingham 1 , Paul Kirumira 2 , Rose Naluyima 2 , Fred Turya 2 , Sylvia Namanda 2 , Morris K Rutakingirwa 2 , Caleb P Skipper 1, 2 , Yofesi Nikweri 3 , Kathy Huppler Hullsiek 1 , Ananta S Bangdiwala 1 , David B Meya 1, 2, 4
Affiliation  

Cryptococcal antigen (CrAg) screening in HIV-infected persons with CD4 < 100 cells/µl can reduce meningitis and death, yet preemptive fluconazole therapy fails in ∼25%. Sertraline has in vitro and in vivo activity against Cryptococcus and is synergistic with fluconazole in mice. We evaluated the efficacy and safety of sertraline in asymptomatic cryptococcal antigenemia. We conducted a randomized trial of asymptomatic CrAg-positive Ugandans from November 2017 to February 2018. All subjects received WHO standard therapy of fluconazole 800 mg for 2 weeks, then 400 mg for 10 weeks, then 200 mg through 24 weeks. Participants were randomized to receive adjunctive sertraline or placebo, given in once-weekly escalating 100 mg/day doses up to 400 mg/day, which was then given for 8 weeks, then tapered. The primary endpoint was meningitis-free 6-month survival. The data and safety monitoring board halted the trial after 21 subjects were enrolled due to safety concerns. Meningitis-free 6-month survival occurred in 9 of 11 of placebo participants and 10 of 10 of sertraline participants. However, seven serious adverse events (SAEs) occurred (n = 4 sertraline group; n = 3 placebo group). Three SAEs in the sertraline group presented with psychosis and aggressive behavioral changes with one meeting Hunter's criteria for serotonin syndrome while receiving 200 mg/day sertraline. Two transient psychoses were associated with antecedent fluconazole and sertraline interruption. The serotonin syndrome resolved within 1 day, but psychosis persisted for 4 months after sertraline discontinuation. Sertraline was associated with excess SAEs of psychosis. Due to early stopping, we were unable to determine any efficacy for cryptococcal antigenemia.

中文翻译:

辅助舍曲林用于无症状隐球菌抗原血症:一项随机临床试验。

在CD4 <100个细胞/微升的HIV感染者中进行隐球菌抗原(CrAg)筛查可以减少脑膜炎和死亡,但先发性氟康唑治疗无效约25%。舍曲林对隐球菌具有体外和体内活性,并且与氟康唑在小鼠中具有协同作用。我们评估了舍曲林在无症状隐球菌抗原血症中的疗效和安全性。我们从2017年11月至2018年2月进行了无症状CrAg阳性乌干达人的随机试验。所有受试者均接受WHO标准的氟康唑治疗,疗程为2周,然后400 mg疗程10周,然后200 mg疗程24周。参与者被随机分配接受舍曲林或安慰剂,每周一次,逐渐增加剂量100 mg /天,最高至400 mg /天,然后给予8周,然后逐渐减量。主要终点是无脑膜炎的6个月生存期。出于安全方面的考虑,数据和安全监控委员会在招募了21名受试者后中止了试验。11名安慰剂参与者中有9名发生了无脑膜炎的6个月生存期,而舍曲林参与者10名中有10名发生了10个月的无脑膜炎。但是,发生了七个严重不良事件(SAE)(n = 4个舍曲林组; n = 3个安慰剂组)。舍曲林组中的三名SAE出现精神病和激进的行为变化,其中一名在接受200 mg / day舍曲林的同时符合Hunter血清素综合征的标准。两种暂时性的精神病与氟康唑和舍曲林的中断有关。血清素综合征在1天之内消失,但是在停用舍曲林后精神病持续了4个月。舍曲林与过度的精神病性SAE相关。
更新日期:2020-05-16
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