Machuca A, Rodés B, Soriano V
Service of Infectious Diseases, Hospital Carlos III, Instituto de Salud Carlos III, Madrid, Spain.
Virus Res. 2001 Oct 30;78(1-2):93-100. doi: 10.1016/s0168-1702(01)00287-8.
No effective treatment for TSP/HAM has been described so far. Interventions with corticosteroids, plasmapheresis, interferon and, more recently, with antiretroviral drugs have been tried with poor results. The main HTLV replication mechanism is thought to be through clonal expansion of HTLV-infected cells, which excludes the involvement of the reverse transcriptase (RT) enzyme. However, a virological and clinical improvement has been noticed in HTLV-I carriers suffering from TSP/HAM receiving zidovudine or lamivudine. Herein, we describe the virological and clinical outcome in two TSP/HAM patients infected with HTLV-I treated with zidovudine plus lamivudine, and in two HTLV-II/HIV-1 co-infected patients receiving triple combinations including lamivudine. While, one TSP/HAM patient experienced a 2 log decrease in HTLV-I proviral load, an increase of 1 log was observed in another patient after several months of treatment with zidovudine plus lamivudine. The two HTLV-II/HIV-1 co-infected patients showed an initial increase in HTLV-II proviral load after beginning HAART followed by a slight decline a few months later. Plasma HIV-1 RNA fell to <50 copies/ml in both patients after beginning therapy. None of the four HTLV positive patients developed genetic changes at the conserved YMDD domain within their respective RT genes, which could be related to lamivudine resistance. No clinical improvement was observed in one TSP/HAM patient after more than 1 year on treatment with nucleoside analogues. The inhibition of the HTLV RT along with the cytostatic effect of some nucleoside analogues, including zidovudine, could reduce HTLV replication, and therefore reduce HTLV proviral load. The clinical consequences of this effect need to be further examined.
迄今为止，尚未发现针对热带痉挛性轻瘫/人类嗜T淋巴细胞病毒I型相关脊髓病（TSP/HAM）的有效治疗方法。曾尝试使用皮质类固醇、血浆置换、干扰素，以及最近使用抗逆转录病毒药物进行干预，但效果不佳。人们认为人类嗜T淋巴细胞病毒（HTLV）的主要复制机制是通过HTLV感染细胞的克隆扩增，这排除了逆转录酶（RT）的参与。然而，接受齐多夫定或拉米夫定治疗的TSP/HAM患者中，已观察到病毒学和临床症状有所改善。在此，我们描述了两名感染HTLV-I的TSP/HAM患者接受齐多夫定加拉米夫定治疗后的病毒学和临床结果，以及两名HTLV-II/HIV-1合并感染患者接受包括拉米夫定在内的三联组合治疗后的情况。一名TSP/HAM患者在接受齐多夫定加拉米夫定治疗数月后，HTLV-I前病毒载量下降了2个对数，而另一名患者则增加了1个对数。两名HTLV-II/HIV-1合并感染患者在开始高效抗逆转录病毒治疗（HAART）后，HTLV-II前病毒载量最初有所增加，几个月后略有下降。两名患者在开始治疗后，血浆HIV-1 RNA均降至<50拷贝/ml。四名HTLV阳性患者在各自的RT基因保守的YMDD结构域均未发生与拉米夫定耐药相关的基因变化。一名TSP/HAM患者在接受核苷类似物治疗1年多后，未观察到临床改善。抑制HTLV RT以及包括齐多夫定在内的一些核苷类似物的细胞生长抑制作用，可能会减少HTLV复制，从而降低HTLV前病毒载量。这种作用的临床后果需要进一步研究。
