Highly active antiretroviral therapy and cardiovascular complications in HIV-infected patients

Highly active antiretroviral therapy (HAART) has prolonged many patients' lives, but many cardiac sequelae of HIV are not affected by HAART and continue to develop even with treatment. In addition, HAART itself causes in a high proportion of patients a metabolic syndrome, characterized by lipodystrophy/ lipoatrophy, dyslipidemia and insulin resistance that may be associated with an increase in peripheral artery and coronary artery diseases. Careful cardiovascular evaluation in the course of HIV disease can identify cardiac complications early enough to treat. All HIV-infected patients who are either candidates to antiretroviral therapy or who are already under treatment should undergo an assessment that includes the evaluation of the cardiovascular risk with the available guidelines and the interactions between antiretrovirals and drugs commonly used to treat cardiovascular disease.     

Highly active antiretroviral therapy and the cardiovascular system: the heart of the matter

Highly active antiretroviral therapy (HAART) has prolonged many patients' lives, but many cardiac sequelae of HIV are not affected by HAART and continue to develop even with treatment. In addition, HAART itself causes in a high proportion of patients a metabolic syndrome, characterized by lipodystrophy/lipoatrophy, dyslipidemia and insulin resistance that may be associated with an increase in coronary artery disease and stroke. Careful cardiovascular evaluation in the course of HIV disease can identify cardiac complications early enough to treat. All HIV-infected patients are candidates for antiretroviral therapy and patients already under treatment should undergo an assessment that includes the evaluation of the cardiovascular risk according to the available guidelines.     

水飞蓟宾胶囊治疗抗艾滋病毒药物致肝损害的效果观察

目的 观察水飞蓟宾胶囊对艾滋病患者抗病毒治疗后出现肝损害的疗效.方法 将82例诊断为因高效抗逆转录病毒治疗后出现药物性肝炎的艾滋病初治患者随机分成对照组40例和治疗组42例,对照组予口服葡醛内酯片（每次0.2 g tid）;治疗组在此基础上加用口服水飞蓟宾胶囊（每次70 mg tid）,疗程2周.结果 治疗后两组患者的丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、谷氨酰转肽酶（GGT）均明显下降,治疗组总有效率与对照组相比差异有统计学意义（P 〈 0.05）,而且治疗组的ALT、AST、GGT恢复率与对照组相比差异有统计学意义（P 〈 0.05）.结论 水飞蓟宾治疗抗艾滋病病毒药物引起的药物性肝炎疗效显著,且用药安全.     

Therapeutic drug monitoring in highly active antiretroviral therapy

Importance of the field: Despite the efficacy of combination antiretroviral therapy (ART), a large proportion of patients living with HIV/AIDS on ART does not achieve or maintain adequate virological suppression. Therapeutic drug monitoring (TDM) has been utilised to improve treatment outcomes of ART.

Areas covered in the review: The potential incorporation of TDM into the clinical HIV management is supported by the existing relationship between drug exposure and efficacy/toxicity, the high inter-patient variability pharmacokinetics, and the accurate, specific and rapid method for drug level determination. The current status of TDM in ART is reviewed in this article with discussions on its feasibility, potential use and limitations.

What the reader will gain: Mounting evidence from clinical trials has indicated the potential use of TDM in reducing the rates of treatment failure and adverse effect, avoiding the drug interactions, and special populations, such as children, pregnant women and patients with co-infections. TDM may play an important role even in resource-limited settings, to safeguard expanded use of bioequivalent generic antiretroviral drugs and avoid drug interactions with traditional Chinese medicines.

Take home message: TDM is still in the centre of controversy in that several critical issues need to be addressed, such as limited adherence assessment, inappropriate response predictors, insufficient validation of target concentration windows and lack of the quality control of assay. The utility of TDM will remain experimental until more data are obtained from large clinical trials showing the benefit of TDM.     

长期接受高效抗逆转录病毒治疗的不良反应研究进展

高效抗逆转录病毒治疗(HAART)已大大提高了获得性免疫缺陷综合征(AIDS)患者的生存年限.人们在设法降低药物成本、增强药物疗效的同时,越来越关注抗逆转录病毒药物的不良反应.后者临床表现多样,短期用药可出现胃肠道症状、过敏反应、药物性肝损害、骨髓抑制及乳酸酸中毒等,长期用药不良反应有脂肪重新分布、胰岛素抵抗、血脂异常及心血管疾病等.本文主要概述长期接受HAART者的不良反应及其发生机制.     

常压氧疗法对降低精神分裂症患者无抽搐电痉挛治疗引起的记忆功能损伤研究

目的研究常压氧疗法对精神分裂症患者无抽搐电痉挛治疗(MECT)对记忆功能的影响。方法选择本院2012年7月至2013年12月84例精神分裂症患者,随机分为2组,每组42例,对照组在每次行MECT后予常规处理,试验组在每次MECT治疗后行常压氧吸氧处理。进行治疗前、治疗后及结束治疗后4周各阶段阳性和阴性症状量表(PANSS)评估,并用韦氏记忆量表(WMS)进行记忆测试。结果对照组与试验组治疗后、结束治疗后4周与治疗前各项指标比较差异均有统计学意义(P<0.05);试验组治疗结束后4周PANSS分别为17.0±3.1和11.0±2.9,低于对照组(分别为19.3±2.9和13.8±2.2),差异具有统计学意义(P<0.05);试验组结束治疗后4周一般病理症状评分为24.9±2.8,低于对照组29.3±2.2(P<0.05);试验组治疗后4周再认和图片评分分别为11.8±1.9和14.2±3.0,高于对照组(分别为10.4±1.2和11.8±1.5)(P<0.05);试验组治疗后4周联想和背数评分分别为15.6±1.2和15.7±2.5,高于对照组(分别为13.3±1.8和13.5±1.9),差异具有统计学意义(P<0.05)。结论常压氧疗法能降低精神分裂症患者MECT引起的记忆功能损伤。     

高效抗逆转录病毒疗法相关性代谢并发症研究进展

高效抗逆转录病毒疗法 (HAART)使人免疫缺陷病毒 (HIV)感染的发病率及病死率明显降低,但常引起代谢并发症,包括脂肪代谢障碍、血脂异常、高血糖、高乳酸血症及骨质疏松等,机制未完全阐明。有报道在接受HAART的HIV阳性病人,提前发生冠心病及心肌梗死的危险性上升。     

河南省艾滋病儿童抗病毒治疗效果分析

目的明确艾滋病（AIDS）儿童抗病毒药物的治疗效果,了解抗病毒治疗对AIDS儿童的生长发育情况的影响。方法符合治疗标准的AIDS儿童给予抗病毒治疗并随访2年,每半年对AIDS儿童的身高、体重及外周血CD4＋T淋巴细胞、病毒载量等进行检测并分析,评估AIDS儿童抗病毒治疗效果及生长发育状况。结果AIDS儿童经一线方案抗病毒治疗后CD4＋T淋巴细胞计数升高,较基线水平差异具有统计学意义（P〈0.05）,二线方案抗病毒治疗后CD4＋T淋巴细胞较基线水平差异无统计学意义（P〉0.05）。AIDS儿童基线身高、体重均低于同龄正常儿童,差异具有统计学意义（P〈0.05）,经抗病毒治疗后身高、体重与同龄正常儿童差距减小,差异具有统计学意义（P〈0.05）。结论抗病毒治疗能够有效提高AIDS儿童机体免疫力,提升儿童的生长发育水平;更早期、更长期的抗病毒治疗能否使AIDS儿童的生长发育水平达到正常,仍需开展进一步的研究。     

治疗性药物监测在高效抗反转录病毒疗法中的应用进展

在HIV病人的治疗中,高效抗反转录病毒疗法(HAART)在降低发病率和病死率方面都有积极作用。然而,用于HAART的抗反转录病毒药物(ARV)在体内代谢中多有相互影响,主要为彼此的抑制或拮抗作用。因此,HAART在临床应用于不同个体时多会有不同的临床效果和不良反应,用药剂量难以把握。治疗性药物监测(TDM)则可检测用药病人的ARV血浆浓度,在此基础上再结合临床疗效而对用药剂量作出调整。本文综述了TDM在HAART中的运用现状、存在问题以及发展前景。     

他汀类药物引起的肝损害

他汀类药物是3-羟基3-甲基戊二酰辅酶A还原酶抑制剂,是目前临床上广泛应用的降脂药物。他汀类药物所致肝损害(SILI)无特殊临床特征,与其他药物所致肝损害类似。SILI以肝细胞型多见,胆汁淤积型不常见,混合型少见。SILI的发生机制可能与药物本身的毒性、继发性效应及免疫机制等有关。高剂量、联合用药、肝病史等是SILI的危险因素。应用他汀类药物期间发生轻度肝损害者可减小药物剂量继续使用;发生中度肝损害者应在减量的同时使用保肝药物;发生严重肝损害者则需停药并采取相应的对症治疗措施。临床医师处方他汀类药物要注意严格掌握用药剂量,加强用药期间的实验室监测,尽量避免联合用药,并应嘱咐患者加强营养、注意休息。肝病患者慎用他汀类药物。大部分患者的SILI是可逆的。     

Leukotriene-mediated liver injury

The pathogenic mechanism of fulminant hepatitis induced by 700 mg/kg D-galactosamine plus 33 micrograms/kg endotoxin was investigated in male NMRI mice. The extent of liver injury was assessed by measurement of serum transaminases and sorbitol dehydrogenase activities 9 hr after intoxication, as well as by histopathological evaluation. When the hepatic glutathione content of galactosamine endotoxin-treated animals had been decreased by more than 90% following administration of 250 mg/kg phorone or 400 mg/kg diethyl maleate given three times, no signs of liver injury were observed. Since different agents interfering with the leukotriene synthesis pathway also prevented galactosamine/endotoxin-induced hepatitis, we suspected that a glutathione-derived peptidoleukotriene may be the pathogenic metabolite. In vivo inhibition of the catabolism of leukotriene C4 by administration of 50 mg/kg of the glutamyl transpeptidase inhibitor AT 125 (Acivicin) also protected the animals against liver injury. In order to elucidate which metabolite of leukotriene C4 was responsible for the observed hepatotoxicity we intravenously injected leukotrienes into animals that had received only galactosamine. Injection of 50 micrograms/kg leukotriene E4 1 hr after galactosamine had no effect. The same dose of leukotriene D4 led to a fulminant hepatitis which was prevented when the leukotriene D4 antagonist FPL 55712 had been given before. In contrast, lipoxygenase inhibitors or AT 125 did not protect against galactosamine + LTD4. Galactosamine/endotoxin-induced and galactosamine/leukotriene D4-induced hepatitis resulted in similarly localized histopathological changes, i.e. diffuse necrosis in the organ. We conclude from our results that galactosamine/endotoxin-induced hepatitis is mediated by a leukotriene D4-dependent mechanism.     

Flucloxacillin-induced liver injury

Flucloxacillin is a common cause of drug-induced liver injury in Europe, affecting in the region of 8.5 in every 100,000 first time users of the drug. The mechanism by which the drug causes the liver injury is currently unknown but it is believed to be influenced by a combination of genetic and environmental factors. This review summarises what is currently known about the disposition of flucloxacillin in the liver, considers potential mechanisms by which flucloxacillin may cause the liver injury, and suggests candidate genes which could determine individual susceptibility to flucloxacillin-induced liver injury.     

Chronic phenytoin therapy-induced vecuronium resistance

This case report highlights a clinically significant pharmacokinetic drug interaction between phenytoin, a widely used anticonvulsant and vecuronium, a non-depolarizing neuromuscular blocker which led to vecuronium resistance.