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Drug Resistance, Rather than Low Tenofovir Levels in Blood or Urine, Is Associated with Tenofovir, Emtricitabine, and Efavirenz Failure in Resource-Limited Settings
AIDS Research and Human Retroviruses ( IF 1.5 ) Pub Date : 2022-06-06 , DOI: 10.1089/aid.2021.0135
Lauren Jennings 1 , Tracy Kellermann 2 , Matthew Spinelli 3 , Zukiswa Nkantsu 1 , Dolphina Cogill 1 , Marije van Schalkwyk 4 , Eric Decloedt 2 , Gert van Zyl 5, 6 , Catherine Orrell 1 , Monica Gandhi 3
Affiliation  

The high cost of viral load (VL) testing limits its use for antiretroviral therapy (ART) adherence support. A low-cost lateral flow urine tenofovir (TFV) rapid assay predicts pre-exposure prophylaxis breakthroughs, but has not yet been investigated in HIV treatment. We therefore evaluated its utility in a pilot cross-sectional study of TFV-containing ART recipients at an increased risk of virologic failure (VF). Participants who had a treatment interruption ≥30 days or had ≥1 episode of viremia (VL ≥400 copies/mL) in the previous year were recruited from a public health setting in Cape Town, South Africa. Self-reported adherence data were collected, the urine TFV assay performed, and concurrent TFV-diphosphate analyzed in dried blood spots. VL testing was done concurrently and, if viremic, genotypic HIV drug resistance testing was performed. Of 48 participants, 18 (37.5%) had VL (>400 copies/mL) at the time of the study, including 16 of 39 receiving efavirenz (EFV), 2 of 6 receiving protease inhibitors, and 0 of 3 receiving dolutegravir. Resistance testing succeeded in 17/18, of which 14 had significant mutations compromising ≥2 agents of the current EFV-based regimen. Of these 14, all had detected urine TFV. Urine TFV was undetectable in two out of three without regimen-relevant resistance; p = .02. In participants on EFV-based regimens returning to care, VF was largely due to viral resistance, where detectable urine TFV had 100% sensitivity (14/14 participants) in predicting resistance. Conversely, when undetectable, the urine-based assay could be used to preclude participants with poor adherence from undergoing costly HIV drug resistance testing.

中文翻译:


在资源有限的环境中,与替诺福韦、恩曲他滨和依非韦伦失败相关的是耐药性,而不是血液或尿液中替诺福韦水平低



病毒载量(VL)检测的高成本限制了其在抗逆转录病毒治疗(ART)依从性支持中的使用。低成本侧流尿替诺福韦 (TFV) 快速检测可预测暴露前预防的突破,但尚未在 HIV 治疗中进行研究。因此,我们在一项针对病毒学失败 (VF) 风险增加的含 TFV ART 接受者的试点横断面研究中评估了其效用。从南非开普敦的公共卫生机构招募了上一年治疗中断≥30天或≥1次病毒血症发作(VL≥400拷贝/mL)的参与者。收集自我报告的依从性数据,进行尿液 TFV 测定,并同时分析干血斑中的 TFV-二磷酸盐。同时进行 VL 检测,如果存在病毒血症,则进行基因型 HIV 耐药性检测。在 48 名参与者中,18 名 (37.5%) 在研究时患有 VL (>400 拷贝/mL),其中 39 名接受依非韦伦 (EFV) 的 16 名,6 名接受蛋白酶抑制剂的 2 名,以及 3 名接受多替拉韦的 0 名。耐药性测试在 17/18 中取得成功,其中 14 例具有显着突变,损害了当前基于 EFV 的方案的 ≥ 2 种药物。这 14 人中,全部检测出尿液 TFV。在没有与治疗方案相关的耐药性的情况下,三分之二的人检测不到尿液 TFV; p = .02。在接受基于 EFV 的治疗方案返回护理的参与者中,室颤主要是由于病毒耐药性,其中可检测的尿液 TFV 在预测耐药性方面具有 100% 的敏感性(14/14 参与者)。相反,当无法检测到时,基于尿液的检测可用于阻止依从性差的参与者进行昂贵的艾滋病毒耐药性检测。
更新日期:2022-06-08
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