Laboratory of Experimental Virology, Department of Medical Microbiology, Amsterdam, the Netherlands.
J Infect Dis. 2012 Nov;206(9):1443-52. doi: 10.1093/infdis/jis502. Epub 2012 Aug 20.
Modern antiretroviral therapy (ART) regimens are widely assumed to forgive modest nonadherence, because virological suppression in plasma is common at adherence levels of >70%. Yet, it is unknown whether human immunodeficiency virus type 1 (HIV-1) replication is completely suppressed at these levels of adherence.
We longitudinally quantified levels of cell-associated HIV-1 RNA and DNA in 40 patients (median duration of successful ART before study initiation, 46 months), whose 1-week adherence to therapy prior to the sampling moments was measured electronically.
Patients were constantly 100% adherent (the optimal-adherence group), demonstrated improving adherence over time (the improving-adherence group), or neither of the above (the poor-adherence group). Adherence never decreased to <70% in any patient, and no rebound in plasma virological levels was observed. Nevertheless, poor adherence but not optimal or improving adherence caused a significant longitudinal increase in cell-associated HIV RNA levels (P = .006). Time-weighted changes and regression slopes of viral RNA load for the poor-adherence group were significantly higher than those for the optimal-adherence group (P < .01).
Because ART only blocks infection of new cells but not viral RNA transcription in cells infected before therapy initiation, the observed effects strongly suggest that modest nonadherence can cause new cycles of HIV-1 replication that are undetectable by commercial plasma viral load assays.
现代抗逆转录病毒疗法（ART）方案被广泛认为可以容忍轻微的不依从，因为在>70%的依从水平下，血浆中的病毒学抑制是常见的。然而，尚不清楚在这些依从水平下，人类免疫缺陷病毒 1 型（HIV-1）复制是否完全被抑制。
我们对 40 例患者（开始研究前成功 ART 的中位持续时间为 46 个月）的细胞相关 HIV-1 RNA 和 DNA 水平进行了纵向定量，这些患者在采样前的 1 周内接受了电子治疗。
患者始终 100%依从（最佳依从组），表现出随着时间的推移依从性提高（改善依从组），或两者均不符合（依从性差组）。在任何患者中，依从性从未下降到<70%，也未观察到血浆病毒学水平反弹。然而，不良依从性而不是最佳或改善依从性导致细胞相关 HIV RNA 水平的显著纵向增加（P=0.006）。不良依从组的病毒 RNA 负荷的时间加权变化和回归斜率明显高于最佳依从组（P<0.01）。
由于 ART 仅阻断新细胞的感染，而不阻断治疗前已感染细胞中的病毒 RNA 转录，因此观察到的效应强烈表明，轻微的不依从可能导致新的 HIV-1 复制周期，这些周期无法通过商业血浆病毒载量检测。
