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首页> 外文期刊>Journal of Medical Virology >Favorable outcome of ex-vivo purging of monocytes after the reintroduction of treatment after interruption in patients infected with multidrug resistant HIV-1.
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Favorable outcome of ex-vivo purging of monocytes after the reintroduction of treatment after interruption in patients infected with multidrug resistant HIV-1.

机译：感染多重耐药性HIV-1的患者中断后重新引入治疗后，单核细胞体外清除的良好结果。

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In multidrug resistant patients treatment interruptions allow the selection of archived wild-type drug-susceptible viruses that compete for the less fit drug-resistant strains. However, the selection of viruses with increased replicative capacity is often followed by a loss of CD4+ T cells. In addition, drug resistant variants later re-emerge limiting the overall clinical benefit of treatment interruption. Blood monocytes are a key component of the HIV reservoir and can be partially removed by a system for purging of myeloid cells (MYP). This study tested the safety and efficacy of MYP on multidrug resistant patients who underwent treatment interruption. Twelve patients were randomized to receive or not six cycles of MYP during treatment interruption. An optimized antiretroviral regimen was reintroduced after the reappearance of a drug susceptible genotype. Following therapy reintroduction, a long lasting increase in CD4+ T cell counts was observed only in the treatment interruption + MYP patients but not in the control patients. Five/six treatment interruption + MYP patients never experienced virological rebound during a median follow up period of 98 weeks. In contrast, 4/6 patients who did not receive MYP never reached complete viral suppression and had a virological rebound after a median of 16.5 weeks after treatment reintroduction. The difference between the two groups in the time to virological rebound was statistically significant (P = 0.021). A consistent decrease of HIV DNA load in CD14+ purified cells was observed only in treatment interruption + MYP patients. These data suggest that MYP can improve the immunological and virological response to treatment interruption.
机译：在具有多重耐药性的患者中，治疗中断允许选择已归档的野生型药物敏感性病毒，这些病毒会竞争不太适合的耐药性菌株。但是，选择复制能力增强的病毒后往往会丢失CD4 + T细胞。另外，抗药性变体随后重新出现，限制了治疗中断的总体临床益处。血液单核细胞是HIV储存库的关键组成部分，可以通过清除髓样细胞（MYP）的系统部分清除。这项研究测试了MYP在接受治疗中断的多药耐药患者中的安全性和有效性。在治疗中断期间，将12例患者随机接受或不接受6个周期的MYP。药物敏感性基因型重新出现后，重新引入了优化的抗逆转录病毒方案。重新引入治疗后，仅在治疗中断+ MYP患者中观察到CD4 + T细胞计数长期持续增加，而在对照患者中未观察到。五分之六的治疗中断+ MYP患者在中位随访期98周内从未经历病毒学反弹。相反，未接受MYP的4/6患者在重新引入治疗后的中位数为16.5周后从未达到完全的病毒抑制，并出现了病毒学反弹。两组在病毒学反弹时间上的差异具有统计学意义（P = 0.021）。仅在中断治疗+ MYP患者中观察到CD14 +纯化细胞中HIV DNA含量的持续下降。这些数据表明，MYP可以改善对治疗中断的免疫学和病毒学应答。

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