Zidovudine plus lamivudine in human T-lymphotropic virus type-I-associated myelopathy: a randomised trial
Zidovudine plus lamivudine in human T-lymphotropic virus type-I-associated myelopathy: a randomised trial
复制标题
DOI：
10.1186/1742-4690-3-63
复制
发表时间：
2006-09-19
期刊：
影响因子：
3.3
通讯作者：
Weber, Jonathan N.
中科院分区：
文献类型：
--
作者：
Taylor, Graham P.;Goon, Peter;Weber, Jonathan N.
背景：没有治疗方法被证明可以持续改善HTLV-1相关性脊髓病的预后。在观察性研究中，齐多夫定和拉米夫定均报告了临床获益。因此，我们进行了一项随机、双盲、安慰剂对照研究，在16名患者中进行了6个月的核苷类似物联合治疗。结果：主要结局是PBMC中HTLV-1前病毒载量和临床指标的变化。次要终点是T细胞亚群和活化和增殖标志物的变化。6例患者停用齐多夫定。两组之间在疼痛、膀胱功能、残疾评分、步态、前病毒负荷或T细胞活化或增殖标志物方面均未观察到显著变化。积极治疗与不明原因的CD 8和非T淋巴细胞计数降低相关。结论：未能检测到临床改善可能是由于这些具有长期临床病史的患者的不可逆神经损伤，未来的研究应针对早期出现的患者。缺乏病毒学效应，但可能反映了这些核苷类似物缺乏体内抗HTLV-1 RT的活性，活性部分的细胞内浓度不足或新细胞感染对维持该感染阶段前病毒负荷的贡献可能相对较小，从而掩盖了RT抑制的效应。
Background: No therapies have been proven to persistently improve the outcome of HTLV-1-associated myelopathy. Clinical benefit has been reported with zidovudine and with lamivudine in observational studies. We therefore conducted a randomised, double blind, placebo controlled study of six months combination therapy with these nucleoside analogues in sixteen patients. Results: Primary outcomes were change in HTLV-1 proviral load in PBMCs and clinical measures. Secondary endpoints were changes in T-cell subsets and markers of activation and proliferation. Six patients discontinued zidovudine. No significant changes in pain, bladder function, disability score, gait, proviral load or markers of T-cell activation or proliferation were seen between the two arms. Active therapy was associated with an unexplained decrease in CD8 and non-T lymphocyte counts. Conclusion: Failure to detect clinical improvement may have been due irreversible nerve damage in these patients with a long clinical history and future studies should target patients presenting earlier. The lack of virological effect but may reflect a lack of activity of these nucleoside analogues against HTLV-1 RT in vivo, inadequate intracellular concentrations of the active moiety or the contribution of new cell infection to maintaining proviral load at this stage of infection may be relatively small masking the effects of RT inhibition.