Persistence of drug-resistant HIV-1 after a structured treatment interruption and its impact on treatment response
Persistence of drug-resistant HIV-1 after a structured treatment interruption and its impact on treatment response
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DOI：
10.1097/00002030-200302140-00010
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发表时间：
2003-02-14
期刊：
影响因子：
3.8
通讯作者：
Petropoulos, CJ
中科院分区：
文献类型：
--
作者：
Deeks, SG;Grant, RM;Petropoulos, CJ
目的：在接受治疗的耐药病毒血症患者中，结构化治疗中断往往会导致药物敏感的HIV-1病毒再次出现。从理论上讲，这可能会让抢救疗法产生更持久的反应。因此，我们研究了一组先前中断治疗的患者对抗逆转录病毒治疗的长期治疗结果，重点关注治疗成功与失败的决定因素。设计：一项关于在治疗中断后恢复治疗的患者对抗逆转录病毒治疗的反应的前瞻性观察性研究。每月进行病毒学和免疫学检查，连续3个月，然后每3个月进行一次。结果：24例患者接受了结构化治疗中断，并在不同的时间段(中位数20周)后恢复治疗。治疗中断后治疗持续时间的中位数为109周。在所有恢复治疗方案的患者中都观察到了短暂的病毒学应答，这些药物不包含他们的阻断前病毒完全敏感的药物。在病毒学失败期间分离的病毒与中断前病毒在基因和表型上相同，复制能力降低，在体内复制的水平与中断前基线相似。相比之下，在开始只包含一种药物的患者中观察到持久的病毒抑制(<；200拷贝/毫升)，而他们的阻断前病毒对这种药物完全敏感。尽管有病毒抑制，但在两名患者中仍可检测到阻断前耐药病毒群。结论：尽管在中断治疗期间和中断治疗后，耐药HIV-1保持在低水平，但仅包含一种完全有效药物的联合方案可能会实现对该病毒群的持久抑制。(C)2003年，里平科特·威廉姆斯·威尔金斯。
Objective: Among treated patients with drug-resistant viremia, structured treatment interruptions often result in the re-emergence of drug-susceptible HIV-1. Theoretically, this may allow for a more durable response to salvage therapy. We therefore studied the long-term treatment outcome to antiretroviral therapy in a cohort of patients who had previously interrupted therapy, focusing on the determinants of treatment success versus failure.Design: A prospective observational study of the response to antiretroviral therapy in patients resuming therapy after a treatment interruption. Virological and immunological studies were performed every month for 3 months and then every 3 months.Results: Twenty-four patients underwent a structured treatment interruption and resumed therapy after a variable period of time (median 20 weeks). The median duration of treatment after the treatment interruption was 109 weeks. A transient virological response was observed in all patients who resumed a regimen containing no drug to which their pre-interruption virus was fully susceptible. Virus isolated during virological failure was genotypically and phenotypically identical to the preinterruption virus, exhibited reduced replicative capacity, and replicated in vivo at levels similar to the pre-interruption baseline. In contrast, durable viral suppression (< 200 copies/ml) was observed in patients who initiated a regimen containing only one drug to which their pre-interruption virus was fully susceptible. Despite viral suppression, the pre-interruption drug-resistant virus population remained detectable in two patients.Conclusion: Although drug-resistant HIV-1 persists at low levels during and after the interruption of therapy, durable suppression of this virus population may be achieved with a combination regimen containing only one fully active agent. (C) 2003 Lippincott Williams Wilkins.