Zidovudine: a review of its use in the management of vertically-acquired pediatric HIV infection.
Zidovudine: a review of its use in the management of vertically-acquired pediatric HIV infection.
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DOI：
10.2165/00128072-200204080-00004
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发表时间：
2002-01-01
期刊：
影响因子：
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通讯作者：
Figgitt, David P
中科院分区：
文献类型：
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作者：
Bhana, Nila;Ormrod, Douglas;Figgitt, David P
未标记：齐多夫定是一种胸腺嘧啶类似物，在细胞内磷酸化为齐多夫定三磷酸代谢物后，抑制hiv特异性逆转录酶并终止前病毒DNA。齐多夫定在产前（100mg口服5次/天），分娩时（2mg /kg静脉注射超过1小时，然后1mg /kg/h），然后给新生儿6周（2mg /kg），显著降低艾滋病毒垂直传播率约三分之二，在没有母乳喂养的情况下（儿科艾滋病临床试验组076试验，标准方案）。较短的齐多夫定治疗方案使非母乳喂养人群的艾滋病毒传播风险降低了50%，使母乳喂养人群的艾滋病毒传播风险降低了37%。齐多夫定（标准方案）联合拉米夫定优于单用齐多夫定。短期口服齐多夫定方案不如两剂量口服奈韦拉平方案有效，尽管短期齐多夫定加拉米夫定联合使用同样有效。在包括其他抗病毒药物的三联治疗方案中，齐多夫定可以抑制新生儿、婴儿和儿童的病毒复制。一项针对未接受治疗的儿童的试验结果表明，齐多夫定和拉米夫定或阿巴卡韦联合使用蛋白酶抑制剂奈非那韦的抗病毒效果优于不使用奈非那韦的联合治疗。当齐多夫定用于其他高活性抗逆转录病毒治疗方案时，替代标志物的显著改善一直可见。改用含利托那韦方案优于改用两种新的核苷类逆转录酶抑制剂治疗。临床试验的短期和长期（长达5.6年）结果表明，除了轻度贫血在治疗停止后自行消退外，产前和新生儿暴露于齐多夫定通常耐受良好。在儿童HIV感染患者的临床试验中，齐多夫定作为单药治疗通常耐受性良好，不良事件与成人报告的相似，贫血和中性粒细胞减少症是最常见的。结论：齐多夫定单药治疗或与其他抗逆转录病毒药物联合使用，仍然是预防母婴艾滋病毒传播的首选治疗方法，其传播率显著降低。在可行的情况下，预防垂直传播的最佳策略是将药物治疗与剖宫产分娩和不母乳喂养结合起来。此外，齐多夫定联合另一种核苷类似物和蛋白酶抑制剂是治疗儿童HIV感染的首选或第二选择疗法，因为血浆和脑脊液中的病毒载量已显示出显著和持续的降低。
UNLABELLED: Zidovudine is a thymidine analog that, after intracellular phosphorylation to zidovudine triphosphate metabolite, inhibits HIV-specific reverse transcriptase and terminates proviral DNA. Zidovudine administered to mildly symptomatic women with HIV infection in the antepartum (100mg orally 5 times/day), intrapartum (2 mg/kg intravenously over 1 hour then 1 mg/kg/h) and then to the neonate for 6 weeks (2 mg/kg), significantly reduced the rate of vertical HIV transmission by about two thirds, in the absence of breast-feeding (The Pediatric AIDS Clinical Trials Group 076 trial, standard protocol). Shorter zidovudine regimens, reduced the risk of transmission of HIV by 50% in a non-breast-feeding population and by about 37% in breast-feeding populations. Zidovudine (standard protocol) in combination with lamivudine was superior to zidovudine alone. A short oral zidovudine regimen was not as effective as a two-dose oral nevirapine regime, although the combination of short-course zidovudine plus lamivudine was as effective. Suppression of viral replication in neonates, infants and children has been achieved with zidovudine when used in triple-therapy regimens that include other antiviral drugs. Results from a trial of treatment-naive children indicate that the antiviral efficacy of combinations of zidovudine and lamivudine or abacavir, given with the protease inhibitor nelfinavir, is superior to treatment with this combination minus nelfinavir. When zidovudine was used in other highly active antiretroviral therapy regimens significant improvements in surrogate markers were consistently seen. Changing to ritonavir-containing regimens was superior to changing to treatment with two new nucleoside reverse transcriptase inhibitors. Short- and long-term (up to 5.6 years) outcomes from clinical trials showed that prenatal and neonatal exposure to zidovudine was generally well tolerated with the exception of mild anemia that resolved spontaneously after treatment cessation. Zidovudine was generally well tolerated as monotherapy in clinical trials of pediatric patients with HIV infection, and adverse events were similar to those reported in adults, with anemia and neutropenia being the most common.CONCLUSION: Zidovudine, as monotherapy or in combination with other antiretroviral agents, remains a first-choice therapy for the prophylaxis of mother-to-child HIV transmission as shown by substantial reductions in transmission rates. Where feasible, the optimal strategy to prevent vertical transmission is to combine drug therapy with Cesarean section delivery and no breast-feeding. In addition, zidovudine in combination with another nucleoside analogue and a protease inhibitor is a first- or second-choice therapy for the treatment of pediatric HIV infection as significant and sustained reductions in viral load have been shown in both plasma and cerebrospinal fluid.