Boillat-Blanco Noémie, Darling Katharine E A, Schoni-Affolter Franziska, Vuichard Danielle, Rougemont Mathieu, Fulchini Rosamaria, Bernasconi Enos, Aouri Manel, Clerc Olivier, Furrer Hansjakob, Günthard Huldrych F, Cavassini Matthias
Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland.
Antivir Ther. 2015;20(2):165-75. doi: 10.3851/IMP2815. Epub 2014 Jun 25.
Management of persistent low-level viraemia (pLLV) in patients on combined antiretroviral therapy (cART) with previously undetectable HIV viral loads (VLs) is challenging. We examined virological outcome and management among patients enrolled in the Swiss HIV Cohort Study (SHCS).
In this retrospective study (2000-2011), pLLV was defined as a VL of 21-400 copies/ml on ≥ three consecutive plasma samples with ≥8 weeks between first and last analyses, in patients undetectable for ≥24 weeks on cART. Control patients had ≥ three consecutive undetectable VLs over ≥32 weeks. Virological failure (VF), analysed in the pLLV patient group, was defined as a VL>400 copies/ml.
Among 9,972 patients, 179 had pLLV and 5,389 were controls. Compared to controls, pLLV patients were more often on unboosted protease inhibitor (PI)-based (adjusted odds ratio [aOR; 95% CI] 3.2 [1.8, 5.9]) and nucleoside/nucleotide reverse transcriptase inhibitor (NRTI)-only combinations (aOR 2.1 [1.1, 4.2]) than on non-nucleoside reverse transcriptase inhibitor and boosted PI-based regimens. At 48 weeks, 102/155 pLLV patients (66%) still had pLLV, 19/155 (12%) developed VF and 34/155 (22%) had undetectable VLs. Predictors of VF were previous VF (aOR 35 [3.8, 315]), unboosted PI-based (aOR 12.8 [1.7, 96]) or NRTI-only combinations (aOR 115 [6.8, 1,952]), and VLs>200 during pLLV (aOR 3.7 [1.1, 12]). No VF occurred in patients with persistent very LLV (21-49 copies/ml; n=26). At 48 weeks, 29/39 patients (74%) who changed cART had undetectable VLs, compared with 19/74 (26%) without change (P<0.001).
Among patients with pLLV, VF was predicted by previous VF, cART regimen and VL≥200. Most patients who changed cART had undetectable VLs 48 weeks later. These findings support cART modification for pLLV>200 copies/ml.
对于接受联合抗逆转录病毒疗法（cART）且既往HIV病毒载量（VL）不可检测的患者，持续性低水平病毒血症（pLLV）的管理具有挑战性。我们在瑞士HIV队列研究（SHCS）的入组患者中研究了病毒学结局及管理情况。
在这项回顾性研究（2000 - 2011年）中，pLLV被定义为在接受cART治疗≥24周后病毒载量不可检测的患者中，连续≥3份血浆样本的病毒载量为21 - 400拷贝/毫升，且首次和末次分析之间间隔≥8周。对照患者在≥32周内连续≥3次病毒载量不可检测。在pLLV患者组中分析的病毒学失败（VF）定义为病毒载量>400拷贝/毫升。
在9972例患者中，179例有pLLV，5389例为对照。与对照相比，pLLV患者更常采用未增强的蛋白酶抑制剂（PI）为基础的方案（校正比值比[aOR；95%可信区间]3.2[1.8, 5.9]）和仅含核苷/核苷酸逆转录酶抑制剂（NRTI）的联合方案（aOR 2.1[1.1, 4.2]），而非非核苷逆转录酶抑制剂和增强PI为基础的方案。48周时，155例pLLV患者中有102例（66%）仍有pLLV，19例（12%）发生VF，34例（22%）病毒载量不可检测。VF的预测因素为既往VF（aOR 35[3.8, 315]）、未增强的PI为基础的方案（aOR 12.8[1.7, 96]）或仅含NRTI的联合方案（aOR 115[6.8, 1952]），以及pLLV期间病毒载量>200（aOR 3.7[1.1, 12]）。持续性极低水平病毒血症（21 - 49拷贝/毫升；n = 26）的患者未发生VF。48周时，39例更换cART的患者中有29例（74%）病毒载量不可检测，而未更换的74例患者中有19例（26%）病毒载量不可检测（P<0.001）。
在pLLV患者中，VF可由既往VF、cART方案和病毒载量≥200预测。大多数更换cART的患者在48周后病毒载量不可检测。这些发现支持对病毒载量>200拷贝/毫升的pLLV患者进行cART调整。
