诱导性,传染性HIV-1的潜藏储备并没有减少,尽管几十年的抗逆转录病毒疗法
Natalie F McMyn1, Joseph Varriale1, Emily J Fray1
1Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
The Journal of clinical investigation
|July 18, 2023
概括
尽管几十年来进行了抗逆转录病毒疗法 (ART),但CD4+T细胞中的潜伏HIV-1储存体并未衰变. 感染细胞的增殖维持了这种储备,强调了终身艾滋病毒治疗的必要性.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 传染性疾病 传染性疾病
背景情况:
- 人类免疫缺陷病毒1型 (HIV-1) 在休息的CD4+T细胞中建立了一个潜在的储存库,尽管抗逆转录病毒治疗 (ART) 仍然存在.
- 最初的研究表明,在ART的前7年 (半衰期为44个月) 中,储衰变缓慢,但长期衰变动态尚不清楚.
- 整合部位的分析表明了对可诱导,完整的前病毒的潜在选择,这增加了几十年ART治疗后治疗中断的希望.
研究的目的:
- 在长期接受ART治疗的个体中研究可诱导,可复制的HIV-1储库的长期动态.
- 为了确定在ART的前7年观察到的缓慢衰变是否会在持续20多年的治疗中继续下去.
主要方法:
- 定量病毒外生测试 (QVOA) 和完整的病毒前DNA测试 (IPDA) 用于测量HIV-1储存器.
- 这项研究包括42名患者,平均持续ART治疗22年.
- 分析的重点是诱导性,复制能力强的前病毒的频率和储库衰变率.
主要成果:
- 与预期相反,可诱导,具有复制能力的HIV-1前病毒的频率在ART治疗7年后没有下降;相反,它显示出增加,估计翻倍时间为23年.
- IPDA证实,长期使用ART时,储衰变 (半衰期为44个月) 不会持续.
- 缺乏衰变的原因是受感染的CD4+T细胞的增殖,这抵消了任何潜在的衰变机制.
结论:
- 尽管整合部位发生了变化,但HIV-1感染的CD4+T细胞的增殖使得诱导性,复制能力强的前病毒的频率在长期内保持在相对恒定的水平.
- 这些发现挑战了几十年的ART可能导致储水池消除,从而使治疗中断的观念.
- 这些结果强烈地加强了终身ART的必要性,以有效地管理HIV-1感染.
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