Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201).
Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201).
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DOI：
10.1371/journal.pone.0095524
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
A5201 study team
中科院分区：
文献类型：
--
作者：
McKinnon JE;Mailliard RB;Swindells S;Wilkin TJ;Borowski L;Roper JM;Bastow B;Kearney M;Wiegand A;Mellors JW;Rinaldo CR;A5201 study team
利托那韦增强阿扎那韦（ATV/r）的简化维持治疗为HIV-1感染提供了一种替代治疗选择，可节省核苷类似物（NRTI）供将来使用并降低毒性。我们假设免疫激活（IA）水平和淋巴细胞群的恢复可能会影响方案简化后的病毒学结果。在ACTG 5201临床试验的背景下，34名接受抗逆转录病毒治疗（2种NRTI加蛋白酶抑制剂）病毒学抑制≥48周的受试者转为单独使用ATV/r。对从25名具有可用样本的患者中分离的PBMC进行流式细胞术分析，其中24名患者的淋巴细胞恢复足以进行本研究。评估包括计数T细胞（CD 4/CD 8）、自然杀伤（NK）（CD 3 + CD 56 + CD 16+）细胞和细胞相关标志物（HLA-DR，CD 38/69/94/95/158/279）。在研究期间，24名患者中有8名患者至少有一次血浆HIV-1 RNA水平（VL）>50拷贝/mL。在回归和生存分析简化后，研究入组时NK细胞水平低于7.1%的组中位数与VL >50拷贝/mL的发展相关（p = 0.043和0.023），比值比为10.3（95%CI：1.92-55.3）。 简化与初始和CD 25 + CD 4 + T细胞的一过性增加相关，对IA水平无影响。方案简化前较低的NK细胞水平预示着核苷类似物停药后病毒学反弹。在48周的临床监测中，方案简化对IA标志物或T淋巴细胞群没有持续影响。ClinicalTrials.gov NCT00084019
Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r) provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI) for future use and decreased toxicity. We hypothesized that the level of immune activation (IA) and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification. Thirty-four participants with virologic suppression ≥48 weeks on antiretroviral therapy (2 NRTI plus protease inhibitor) were switched to ATV/r alone in the context of the ACTG 5201 clinical trial. Flow cytometric analyses were performed on PBMC isolated from 25 patients with available samples, of which 24 had lymphocyte recovery sufficient for this study. Assessments included enumeration of T-cells (CD4/CD8), natural killer (NK) (CD3+CD56+CD16+) cells and cell-associated markers (HLA-DR, CD's 38/69/94/95/158/279). Eight of the 24 patients had at least one plasma HIV-1 RNA level (VL) >50 copies/mL during the study. NK cell levels below the group median of 7.1% at study entry were associated with development of VL >50 copies/mL following simplification by regression and survival analyses (p = 0.043 and 0.023), with an odds ratio of 10.3 (95% CI: 1.92–55.3). Simplification was associated with transient increases in naïve and CD25+ CD4+ T-cells, and had no impact on IA levels. Lower NK cell levels prior to regimen simplification were predictive of virologic rebound after discontinuation of nucleoside analogs. Regimen simplification did not have a sustained impact on markers of IA or T lymphocyte populations in 48 weeks of clinical monitoring. ClinicalTrials.gov NCT00084019
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