Precise Quantitation of the Latent HIV-1 Reservoir: Implications for Eradication Strategies
Precise Quantitation of the Latent HIV-1 Reservoir: Implications for Eradication Strategies
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DOI：
10.1093/infdis/jiv218
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发表时间：
2015-11-01
影响因子：
6.4
通讯作者：
Archin, Nancie M.
中科院分区：
文献类型：
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作者：
Crooks, Amanda M.;Bateson, Rosalie;Archin, Nancie M.
定量病毒生长试验（QVOA）提供了静息CD4（+）T细胞感染（静息细胞感染[RCI]）储库的精确最小估计值。然而，在抗逆转录病毒治疗（ART）期间，RCI随时间的变化，与评估潜伏期逆转剂或其他干预措施的潜在影响有关，尚未得到充分描述。我们对37例接受稳定的抑制性ART治疗6年的人类免疫缺陷病毒（HIV）感染患者的静息CD4（+）T细胞进行了QVOA。一旦HIV RNA水平≥ 6个月，研究在急性（n = 17）或慢性（n = 20）HIV感染期间开始ART的患者。使用160个RCI测量值的随机效应分析，我们发现RCI随时间显著下降（P <0.001），估计平均半衰期为3.6年（95%置信区间，2.3 - 8.1年），与先前研究的结果非常一致。没有证据表明抑制≥ 6个月的患者的急性HIV感染比慢性HIV感染衰减更快（P = 0.99）。RCI是可靠的估计与纵向测量一般显示6倍是罕见的。我们认为，6倍的下降是一个相关的阈值，可靠地确定抗潜伏期干预措施对RCI的影响。
The quantitative viral outgrowth assay (QVOA) provides a precise minimal estimate of the reservoir of resting CD4(+) T-cell infection (resting cell infection [RCI]). However, the variability of RCI over time during antiretroviral therapy (ART), relevant to assess potential effects of latency-reversing agents or other interventions, has not been fully described. We performed QVOA on resting CD4(+) T cells obtained via leukapheresis from 37 human immunodeficiency virus (HIV)-infected patients receiving stable suppressive ART for a period of 6 years. Patients who started ART during acute (n = 17) or chronic (n = 20) HIV infection were studied once HIV RNA levels were = 6 months. Using random effects analysis of 160 RCI measurements, we found that RCI declined significantly over time (P < .001), with an estimated mean half-life of 3.6 years (95% confidence interval, 2.3-8.1 years), remarkably consistent with findings of prior studies. There was no evidence of more rapid decay in acute versus chronic HIV infection (P = .99) for patients suppressed a >= 6 months. RCI was reliably estimated with longitudinal measurements generally showing 6-fold were rare. We suggest that a 6-fold decline is a relevant threshold to reliably identify effects of antilatency interventions on RCI.