Background An zidovudine （AZT）-substitution regimen containing 24-week stavudine （d4T） followed by long-term AZT for HIV therapy is potential to trade off short-term AZT-related anemia and long-term risks associat...Background An zidovudine （AZT）-substitution regimen containing 24-week stavudine （d4T） followed by long-term AZT for HIV therapy is potential to trade off short-term AZT-related anemia and long-term risks associated with d4T in resourcelimited settings.However,evidence is scarce.This study aims to assess the efficacy and safety of AZT-substitution regimen,aiming to find a regimen with better efficacy,less adverse events,and more affordability in resource-limited settings.Methods This prospective,multicenter study enrolled 499 （190 on d4T regimen,172 on AZT regimen,and 137 on AZT-substitution regimen） HIV-1-infected subjects who initiated combined antiretroviral therapy and attended follow-up visits over 96 weeks from 2009 to 2011.Lamivudine （3TC） and either nevirapine （NVP） or efavirenz （EFV） were the other two drugs in the antiretroviral regimens.Virologic and immunologic responses and adverse events were monitored at baseline and at weeks 4,12,24,36,48,60,72,84,and 96.Results In terms of hematological adverse effects,AZT-substitution group had similar safety profiles to d4T group and was superior to AZT group.In comparison with AZT-substitution group,AZT group was associated with higher risk of developing anemia （adjusted hazard ratio （aHR）for anemia ≥ grade Ⅱ,8.44,95％ CI 1.81-39.46） and neutropenia （aHR for neutropenia ≥ grade Ⅱ,1.86,95％ CI 1.19-2.93）.The prevalence of lipodystrophy in d4T group was 19.5％,while that in AZT-substitution group was zero.As to antiretroviral efficacy,these three groups showed no differences.Conclusion AZT-substitution regimen provides a relatively safe and effective first-line antiretroviral strategy in resource-limited settings.展开更多
目的系统评价单独应用齐多夫定(zidovudine,ZDV)阻断HIV母婴传播的有效性和安全性。方法采用Cochrane系统评价方法,计算机检索Cochrane图书馆(2007第1期)、PubMed、EMbase、CINAHL、AIDSearch、AIDSLINE、AIDSTRIALS、AIDSDRUGS、AIDSi...目的系统评价单独应用齐多夫定(zidovudine,ZDV)阻断HIV母婴传播的有效性和安全性。方法采用Cochrane系统评价方法,计算机检索Cochrane图书馆(2007第1期)、PubMed、EMbase、CINAHL、AIDSearch、AIDSLINE、AIDSTRIALS、AIDSDRUGS、AIDSinfo、CRD(center of review and dissemination)、CBMdisc,VIP和CNKI等数据库,以及全球或地区性AIDS相关的会议论文集、政府或非政府组织的相关文件等,检索日期截至2007年4月30日,全面收集全球抗艾滋病病毒药物预防HIV母婴传播的随机对照试验。由两名评价员独立筛查文献、评价质量和提取资料,然后交叉核对,若遇分歧则征求第三方意见讨论解决。使用RevMan软件进行Meta分析。结果共纳入8个RCT,包括24篇全文和13篇摘要,其方法学质量的Jadad评分≥3分。Meta分析显示:①ZDV与安慰剂比较共纳入4个RCTs(2385例),无论长短疗程、母乳或非母乳喂养人群,ZDV预防HIV母婴传播的效果均优于安慰剂组,降低HIV母婴传播风险43%～50%,且两组死产率、婴儿死亡率、母亲死亡率、早产、低体重儿、出生缺陷、母婴不良反应发生率和母亲产前、产时和产后并发症发生率差异均无统计学意义(P>0.05)。②1个大样本RCT(1437例)比较了ZDV不同疗程的效果,结果显示ZDV“长–长疗程”(从孕28周开始到产后6周)比“短–短疗程”(从孕35周开始到分娩后3天)降低HIV母婴传播风险61%[RR=0.39,95%CI(0.19,0.82)]。长–长疗程与长–短疗程(从孕28周开始到产后3天)及短-长疗程(从孕35周开始到产后6周)比较,其预防HIV母婴传播的效果差异均无统计学意义(P>0.05)。各组死产、新生儿死亡、1年内婴儿死亡、母亲死亡、早产、低体重儿、出生缺陷、母婴不良反应发生率相似(P>0.05)。③1个大样本RCT(1200例)显示:人工喂养+短程ZDV预防HIV母婴传播的效果优于母乳喂养+长程ZDV,可降低婴儿HIV感染风险的35%～39%,但提高了婴儿7个月时�展开更多
目的:研究齐多夫定三联高效抗逆转录病毒治疗对HIVAIDS感染患儿T淋巴细胞及亚群的影响。方法:将在本院就诊的150例艾滋病患儿纳入研究对象,随机分为3组,高效抗逆转录病毒治疗(highly active antiretroviral therapy,HAART)组接受齐多夫...目的:研究齐多夫定三联高效抗逆转录病毒治疗对HIVAIDS感染患儿T淋巴细胞及亚群的影响。方法:将在本院就诊的150例艾滋病患儿纳入研究对象,随机分为3组,高效抗逆转录病毒治疗(highly active antiretroviral therapy,HAART)组接受齐多夫定、拉米夫定、奈韦拉平三联高效抗逆转录病毒治疗,核苷类反转录酶抑制剂(NRTIs)组接受齐多夫定治疗,非核苷类反转录酶抑制剂(NNRTIs)组接受奈韦拉平治疗。治疗后6个月时,检测检测HIV抗体阳性情况、HIV-RNA阳性情况以及外周血中CD3+T细胞、CD4+T细胞、CD8+T细胞含量。结果:(1)HIV感染情况:治疗后6个月时,HAART组的HIV-RNA阳性率/HIV-RNA阳性率均低于NRTIs组和NNRTIs组(4.00%vs.18.00%vs.24.00%,6.00%vs.22.00%vs.20.00%);(2)T淋巴细胞亚群含量:3组的CD4+T细胞、CD8+T细胞的含量有差异,且HAART组的CD4+T细胞含量高于NRTIs组和NNRTIs组(37.24±5.47 vs.25.82±4.24 vs.24.69±3.95),CD8+T细胞含量低于NRTIs组和NNRTIs组(22.94±3.29vs.29.21±4.05 vs.30.46±4.59)。结论:齐多夫定三联高效抗逆转录病毒治疗有助于抑制HIV病毒,调节T淋巴细胞亚群含量,提高机体的细胞免疫功能。展开更多
Background The pharmacokinetics of zidovudine （AZT） are possibly influenced by weight, age, sex, liver and renal functions, severity of disease, and ethnicity. Currently, little information is available on the stead...Background The pharmacokinetics of zidovudine （AZT） are possibly influenced by weight, age, sex, liver and renal functions, severity of disease, and ethnicity. Currently, little information is available on the steady-state pharmacokinetics of AZT in Chinese HIV-infected patients. The current study aimed to characterize the steady-state pharmacokinetics of AZT in a Chinese set-up. Methods Eleven Chinese HIV-infected patients were involved in the steady-state pharmacokinetic study. In total, 300 mg of AZT, as a part of combination therapy, was given to patients, and serial blood samples were collected for 12 hours. The samples were measured by a high-performance liquid chromatography （HPLC） assay, and the results were analyzed by both the non-compartment model and the one-compartment model. Results The Cmax of AZT in Chinese patients was higher than that in non-Asian patients. The half-life of AZT, analyzed by the non-compartment model （P=-0.02）, in male patients （（1.02±0.22） hours） was shorter than that of AZT in female patients （（1.55±0.29） hours）. The AZT clearance, analyzed by the one-compartment model （P=0.045）, in male patients （（262.60±28.13） L/h） was higher than that in female patients （（195.85±60.51） L/h）. Conclusion The present study provides valuable information for the clinical practice of AZT-based highly active antiretroviral therapy in a Chinese set-up.展开更多
文摘Background An zidovudine （AZT）-substitution regimen containing 24-week stavudine （d4T） followed by long-term AZT for HIV therapy is potential to trade off short-term AZT-related anemia and long-term risks associated with d4T in resourcelimited settings.However,evidence is scarce.This study aims to assess the efficacy and safety of AZT-substitution regimen,aiming to find a regimen with better efficacy,less adverse events,and more affordability in resource-limited settings.Methods This prospective,multicenter study enrolled 499 （190 on d4T regimen,172 on AZT regimen,and 137 on AZT-substitution regimen） HIV-1-infected subjects who initiated combined antiretroviral therapy and attended follow-up visits over 96 weeks from 2009 to 2011.Lamivudine （3TC） and either nevirapine （NVP） or efavirenz （EFV） were the other two drugs in the antiretroviral regimens.Virologic and immunologic responses and adverse events were monitored at baseline and at weeks 4,12,24,36,48,60,72,84,and 96.Results In terms of hematological adverse effects,AZT-substitution group had similar safety profiles to d4T group and was superior to AZT group.In comparison with AZT-substitution group,AZT group was associated with higher risk of developing anemia （adjusted hazard ratio （aHR）for anemia ≥ grade Ⅱ,8.44,95％ CI 1.81-39.46） and neutropenia （aHR for neutropenia ≥ grade Ⅱ,1.86,95％ CI 1.19-2.93）.The prevalence of lipodystrophy in d4T group was 19.5％,while that in AZT-substitution group was zero.As to antiretroviral efficacy,these three groups showed no differences.Conclusion AZT-substitution regimen provides a relatively safe and effective first-line antiretroviral strategy in resource-limited settings.
文摘目的系统评价单独应用齐多夫定(zidovudine,ZDV)阻断HIV母婴传播的有效性和安全性。方法采用Cochrane系统评价方法,计算机检索Cochrane图书馆(2007第1期)、PubMed、EMbase、CINAHL、AIDSearch、AIDSLINE、AIDSTRIALS、AIDSDRUGS、AIDSinfo、CRD(center of review and dissemination)、CBMdisc,VIP和CNKI等数据库,以及全球或地区性AIDS相关的会议论文集、政府或非政府组织的相关文件等,检索日期截至2007年4月30日,全面收集全球抗艾滋病病毒药物预防HIV母婴传播的随机对照试验。由两名评价员独立筛查文献、评价质量和提取资料,然后交叉核对,若遇分歧则征求第三方意见讨论解决。使用RevMan软件进行Meta分析。结果共纳入8个RCT,包括24篇全文和13篇摘要,其方法学质量的Jadad评分≥3分。Meta分析显示:①ZDV与安慰剂比较共纳入4个RCTs(2385例),无论长短疗程、母乳或非母乳喂养人群,ZDV预防HIV母婴传播的效果均优于安慰剂组,降低HIV母婴传播风险43%～50%,且两组死产率、婴儿死亡率、母亲死亡率、早产、低体重儿、出生缺陷、母婴不良反应发生率和母亲产前、产时和产后并发症发生率差异均无统计学意义(P>0.05)。②1个大样本RCT(1437例)比较了ZDV不同疗程的效果,结果显示ZDV“长–长疗程”(从孕28周开始到产后6周)比“短–短疗程”(从孕35周开始到分娩后3天)降低HIV母婴传播风险61%[RR=0.39,95%CI(0.19,0.82)]。长–长疗程与长–短疗程(从孕28周开始到产后3天)及短-长疗程(从孕35周开始到产后6周)比较,其预防HIV母婴传播的效果差异均无统计学意义(P>0.05)。各组死产、新生儿死亡、1年内婴儿死亡、母亲死亡、早产、低体重儿、出生缺陷、母婴不良反应发生率相似(P>0.05)。③1个大样本RCT(1200例)显示:人工喂养+短程ZDV预防HIV母婴传播的效果优于母乳喂养+长程ZDV,可降低婴儿HIV感染风险的35%～39%,但提高了婴儿7个月时�
基金This study was supported by the grants from the National Key Technologies R＆D Program for the llth Five-year Plan （No. 2008ZX10001-006） and the National Natural Science Foundation of China （No. 81071372）.
文摘Background The pharmacokinetics of zidovudine （AZT） are possibly influenced by weight, age, sex, liver and renal functions, severity of disease, and ethnicity. Currently, little information is available on the steady-state pharmacokinetics of AZT in Chinese HIV-infected patients. The current study aimed to characterize the steady-state pharmacokinetics of AZT in a Chinese set-up. Methods Eleven Chinese HIV-infected patients were involved in the steady-state pharmacokinetic study. In total, 300 mg of AZT, as a part of combination therapy, was given to patients, and serial blood samples were collected for 12 hours. The samples were measured by a high-performance liquid chromatography （HPLC） assay, and the results were analyzed by both the non-compartment model and the one-compartment model. Results The Cmax of AZT in Chinese patients was higher than that in non-Asian patients. The half-life of AZT, analyzed by the non-compartment model （P=-0.02）, in male patients （（1.02±0.22） hours） was shorter than that of AZT in female patients （（1.55±0.29） hours）. The AZT clearance, analyzed by the one-compartment model （P=0.045）, in male patients （（262.60±28.13） L/h） was higher than that in female patients （（195.85±60.51） L/h）. Conclusion The present study provides valuable information for the clinical practice of AZT-based highly active antiretroviral therapy in a Chinese set-up.
