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台湾地区晚期人类免疫缺陷病毒感染者中与高效抗逆转录病毒治疗相关的致命性乳酸性酸中毒

Fatal lactic acidosis associated with highly active antiretroviral therapy in patients with advanced human immunodeficiency virus infection in Taiwan.

作者信息

Sheng W H, Hsieh S M, Lee S C, Chen M Y, Wang J T, Hung C C, Chang S C

机构信息

Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan 100.

出版信息

Int J STD AIDS. 2004 Apr;15(4):249-53. doi: 10.1258/095646204773557785.

Abstract

Lactic acidosis (LA), a rare but life-threatening adverse effect associated with antiretroviral therapy, has been reported with an increasing frequency since the mid-1990s. From June 1994 to June 2002, a total of six patients, four males and two females with a median age of 43 years (range, 30 to 74 years), had been diagnosed with LA. The estimated incidence of LA was 5.1 per 1000 patient-years (PYs) on highly active antiretroviral therapy (HAART) (95% confidence interval [95% CI], 4.5-5.5 per 1000 PYs) and 4.4 per 1000 PY on nucleoside analogues (NAs) (95% CI, 3.9-4.7 per 1000 PYs). Their median body mass index at diagnosis of LA was 17.6 kg/m(2) (range 16.3 to 22.6 kg/m(2)). The median CD4+ lymphocyte count at the initial diagnosis of HIV infection and at the onset of LA was 38 cells/ micro L (range, 4 to 103 cells/ micro L) and 108 cells/ micro L (range, 79 to 224 cells/ micro L), respectively. The most common symptoms were nausea, vomiting, and dyspnoea. All of the patients had findings suggestive of NA-related mitochondrial toxicity, such as myositis, pancreatitis, fatty hepatitis, peripheral neuropathy or lipodystrophy. The prescribed NA related to LA were stavudine in six patients, lamivudine, five, and didanosine, one. Despite treatment, all patients died of persistent circulatory collapse following LA. The median duration from diagnosis to death was eight days (range, 4-17 days). Our report highlights that clinicians caring for patients with AIDS should be alerted to the potentially fatal LA associated with antiretroviral therapy when patients present with low body mass index, lipodystrophy, unexplained abdominal symptoms, dyspnoea, or elevated aminotransferases.

摘要

乳酸性酸中毒(LA)是一种与抗逆转录病毒疗法相关的罕见但危及生命的不良反应,自20世纪90年代中期以来,其报告频率不断增加。1994年6月至2002年6月,共有6例患者被诊断为LA,其中4例男性,2例女性,中位年龄为43岁(范围30至74岁)。在高效抗逆转录病毒疗法(HAART)中,LA的估计发病率为每1000患者年(PYs)5.1例(95%置信区间[95%CI],每1000 PYs 4.5 - 5.5例),在核苷类似物(NAs)治疗中为每1000 PYs 4.4例(95%CI,每1000 PYs 3.9 - 4.7例)。他们在诊断LA时的中位体重指数为17.6 kg/m²(范围16.3至22.6 kg/m²)。在初次诊断HIV感染时以及LA发作时,CD4⁺淋巴细胞计数的中位数分别为38个细胞/微升(范围4至103个细胞/微升)和108个细胞/微升(范围79至224个细胞/微升)。最常见的症状是恶心、呕吐和呼吸困难。所有患者均有提示与NA相关的线粒体毒性的表现,如肌炎、胰腺炎、脂肪性肝炎、周围神经病变或脂肪代谢障碍。与LA相关的所开具的NA药物中,司他夫定有6例患者使用,拉米夫定有5例,去羟肌苷有1例。尽管进行了治疗,所有患者均死于LA后的持续性循环衰竭。从诊断到死亡的中位持续时间为8天(范围4至17天)。我们的报告强调,当艾滋病患者出现低体重指数、脂肪代谢障碍、不明原因的腹部症状、呼吸困难或转氨酶升高时,诊治这些患者的临床医生应警惕与抗逆转录病毒疗法相关的潜在致命性LA。

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