Virological and immunological effects of treatment interruptions in HIV-1 infected patients with treatment failure
Virological and immunological effects of treatment interruptions in HIV-1 infected patients with treatment failure
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DOI：
10.1097/00002030-200012220-00007
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发表时间：
2000-12-22
期刊：
影响因子：
3.8
通讯作者：
Staszewski, S
中科院分区：
文献类型：
--
作者：
Miller, V;Sabin, C;Staszewski, S
目的：分析治疗失败和多重耐药病毒的 HIV-1 感染患者中治疗中断的免疫学和病毒学影响。方法：对 48 名中断治疗（大于或等于 2 个月）的患者，使用抗病毒图评估药物敏感性，并基于群体和克隆测序进行基因型分析。结果：治疗中断导致病毒载量增加（平均 0.7 log(10) 拷贝/ml；P = 0.0001）和 CD4 细胞计数减少（平均 89 x 10(6) 细胞/升；P = 0.0001）。在 28/45 名患者中观察到在表型、基因型和克隆水平上完全转变为野生型病毒。这些患者与那些未表现出向野生型转变的患者的不同之处在于基线 CD4 细胞计数（192 与 59 x 10(6) 细胞/I；P = 0.007）以及基线病毒载量和 CD4 细胞计数之间的关系（无相关与显着负相关；P = 0.008）。随着病毒载量的增加，重新开始治疗的反应下降[相对危险 (RH) 0.33； P = 0.001]并且随着敏感性降低的药物总数的增加（RH 0.51；P = 0.0003）；随着新药数量的增加（RH 2.12；P = 0.0002）和向野生型的转变（RH 5.22，P = 0.006），这种情况有所改善。结论：替代标记的变化表明，尽管存在病毒学失败和耐药病毒，但治疗仍能带来益处。尽管转为野生型病毒的患者在短期内对重新开始治疗的反应更好，但长期影响尚不清楚，需要仔细考虑免疫恶化的风险。 (C) 2000 年利平科特·威廉姆斯和威尔金斯。
Objective: To analyse the immunological and virological effects of treatment interruptions in HIV-1-infected patients with treatment failure and multidrug-resistant virus.Methods: Drug susceptibility was assessed using Antivirogram and genotypic analysis was based on population and clonal sequencing for 48 patients who had interrupted treatment (greater than or equal to 2 months).Results: Treatment interruption resulted in viral load increases (mean 0.7 log(10) copies/ml; P = 0.0001) and CD4 cell count decreases (mean 89 x 10(6) cells/l; P = 0.0001). A complete shift to wild-type virus at the phenotypic, genotypic and clonal level was observed in 28/45 patients. These patients differed from those that did not show a shift to wild type in baseline CD4 cell counts (192 versus 59 x 10(6) cells/I; P = 0.007) and in the relationship between baseline viral load and CD4 cell count (no correlation versus a significant negative correlation; P = 0.008). Response to re-initiation of treatment fell with increasing viral load [relative hazard (RH) 0.33; P = 0.001] and with increasing total number of drugs with reduced susceptibility (RH 0.51; P = 0.0003); it improved with the number of new drugs received (RH 2.12; P = 0.0002) and a shift to wild type (RH 5.22, P = 0.006).Conclusions: Changes in surrogate markers suggest that treatment provided benefit in spite of virological failure and resistant virus. Although patients with a shift to wildtype virus responded better in the short term to treatment re-initiation, the long-term effects are not known and the risk of immune deterioration needs to be carefully considered. (C) 2000 Lippincott WiIliams & Wilkins.