■治疗简化策略是以患者为中心的管理的重要工具。我们评估了PI单一疗法转换策略的长期结果。
■参加43个英国治疗中心的合格参与者在联合ART治疗至少24周内的病毒载量(VL)低于50拷贝/ml。参与者被随机分配以维持正在进行的三联疗法(OT)或切换到医生选择的PI单一疗法(PI-mono)的策略,如果VL反弹,则迅速返回联合疗法。主要结果,此前报道,三年后失去了未来的药物选择,定义为对至少一种药物的新的中/高水平耐药,参与者的病毒在试验进入时被认为是敏感的。在这里,我们报告了在常规护理中进一步延长随访后的耐药性和疾病结局。该研究注册为ISRCTN04857074。
■我们在2008年11月4日至2010年7月28日之间将587名参与者随机分配到OT(291)或PI-mono(296),并跟踪他们的中位数超过8年(100个月),直到2018年。在这个后续时间结束时,OT组的7名参与者和PI-mono组的6名参与者失去了一种或多种未来的药物选择;估计8年的累积风险分别为2.7%和2.1%(差异-0.6%,95%CI-3.2%至2.0%)。只有一名PI-mono参与者对他们正在服用的蛋白酶抑制剂(阿扎那韦)产生了抗性。严重临床事件(死亡,严重的艾滋病,和严重的非AIDS)很少发生;在整个随访期间,OT组共有12名(4.1%)参与者,PI-mono组共有23名(7.8%)参与者(P=0.08)。
■PI单药治疗的策略,定期监测VL,并在反弹后及时重新引入联合治疗,保留了未来的治疗选择。研究结果证实了PI类药物耐药性的高遗传障碍,这使得它们非常适合创造性,以病人为中心,治疗简化方法。不能排除PI单药治疗策略的严重临床事件的小的额外风险的可能性。
■国家卫生研究所卫生技术评估计划。
UNASSIGNED: Treatment-
simplification strategies are important tools for patient-centred management. We evaluated long-term outcomes from a PI monotherapy switch strategy.
UNASSIGNED: Eligible participants attending 43 UK treatment centres had a viral load (VL) below 50 copies/ml for at least 24 weeks on combination ART. Participants were randomised to maintain ongoing triple therapy (OT) or switch to a strategy of physician-selected PI monotherapy (PI-mono) with prompt return to combination therapy if VL rebounded. The primary outcome, previously reported, was loss of future drug options after 3 years, defined as new intermediate/high level resistance to at least one drug to which the participant\'s virus was considered sensitive at trial entry. Here we report resistance and disease outcomes after further extended follow-up in routine care. The study was registered as ISRCTN04857074.
UNASSIGNED: We randomised 587 participants to OT (291) or PI-mono (296) between Nov 4, 2008, and July 28, 2010 and followed them for a median of more than 8 years (100 months) until 2018. At the end of this follow-up time, one or more future drug options had been lost in 7 participants in the OT group and 6 in the PI-mono group; estimated cumulative risk by 8 years of 2.7% and 2.1% respectively (difference -0.6%, 95% CI -3.2% to 2.0%). Only one PI-mono participant developed resistance to the protease inhibitor they were taking (atazanavir). Serious clinical events (death, serious AIDS, and serious non-AIDS) were infrequent; reported in a total of 12 (4.1%) participants in the OT group and 23 (7.8%) in the PI-mono group (P = 0.08) over the entire follow-up period.
UNASSIGNED: A strategy of PI monotherapy, with regular VL monitoring and prompt reintroduction of combination treatment following rebound, preserved future treatment options. Findings confirm the high genetic barrier to resistance of the PI drug class that makes them well suited for creative, patient-centred, treatment-
simplification approaches. The possibility of a small excess risk of serious clinical events with the PI monotherapy strategy cannot be excluded.
UNASSIGNED: The National Institute for Health Research Health Technology Assessment programme.