Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy
Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy
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DOI：
10.1093/infdis/jiaa532
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发表时间：
2021-01-15
影响因子：
6.4
通讯作者：
Mellors, John W.
中科院分区：
文献类型：
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作者：
Gandhi, Rajesh T.;Cyktor, Joshua C.;Mellors, John W.
背景。HIV-1原病毒在接受抗逆转录病毒治疗（ART）的人体内持续存在，但大多数是有缺陷的，不构成具有复制能力的储存库。与有缺陷的HIV-1原病毒相比，携带完整HIV-1原病毒的感染细胞的衰变在使用art方法的人群中尚未得到很好的定义。我们分别量化了长期抗逆转录病毒治疗人群的完整和缺陷原病毒、残留血浆病毒血症以及炎症和激活标志物。在接受抗逆转录病毒治疗后中位时间为7.1年至12年的40名参与者中，完整的原病毒水平随着时间的推移显著下降（中位半衰期为7.1年；95%可信区间[CI]， 3.9-18），而缺陷的原病毒水平没有下降。总HIV-1 DNA的中位半衰期为41.6年（95% CI, 13.6-75）。所有原病毒完好无损的比例随着抗逆转录病毒治疗时间的推移而减少，从第一次抗逆转录病毒治疗时的约10%降至最后一次抗逆转录病毒治疗时的约5%。抗逆转录病毒治疗中完整的原病毒水平与HIV-1总DNA和残留血浆病毒血症相关，但没有证据表明完整的原病毒水平与炎症或免疫激活之间存在关联。在抑制性抗逆转录病毒治疗期间，含有完整的、具有复制能力的原病毒的细胞被选择性地丢失。确定所涉及的机制应该为加速HIV-1水库枯竭的战略提供信息。
Background. HIV-1 proviruses persist in people on antiretroviral therapy (ART) but most are defective and do not constitute a replication-competent reservoir. The decay of infected cells carrying intact compared with defective HIV-1 proviruses has not been well defined in people on ART.Methods. We separately quantified intact and defective proviruses, residual plasma viremia, and markers of inflammation and activation in people on long-term ART.Results. Among 40 participants tested longitudinally from a median of 7.1 years to 12 years after ART initiation, intact provirus levels declined significantly over time (median half-life, 7.1 years; 95% confidence interval [CI], 3.9-18), whereas defective provirus levels did not decrease. The median half-life of total HIV-1 DNA was 41.6 years (95% CI, 13.6-75). The proportion of all proviruses that were intact diminished over time on ART, from about 10% at the first on-ART time point to about 5% at the last. Intact provirus levels on ART correlated with total HIV-1 DNA and residual plasma viremia, but there was no evidence for associations between intact provirus levels and inflammation or immune activation.Conclusions. Cells containing intact, replication-competent proviruses are selectively lost during suppressive ART. Defining the mechanisms involved should inform strategies to accelerate HIV-1 reservoir depletion.