Labhardt Niklaus D, Bader Joëlle, Lejone Thabo Ishmael, Ringera Isaac, Hobbins Michael A, Fritz Christiane, Ehmer Jochen, Cerutti Bernard, Puga Daniel, Klimkait Thomas
Medical Services and Diagnostic, Clinical Research Unit, Swiss Tropical and Public Health Institute University of Basel Molecular Virology, Department Biomedicine-Petersplatz, University of Basel, Basel, Switzerland SolidarMed, Swiss Organization for Health in Africa, Maseru, Lesotho SolidarMed, Swiss Organization for Health in Africa, Luzern, Switzerland Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Medicine (Baltimore). 2016 Jul;95(28):e3985. doi: 10.1097/MD.0000000000003985.
The World Health Organization (WHO) guidelines on antiretroviral therapy (ART) define treatment failure as 2 consecutive viral loads (VLs) ≥1000 copies/mL. There is, however, little evidence supporting 1000 copies as an optimal threshold to define treatment failure. Objective of this study was to assess the correlation of the WHO definition with the presence of drug-resistance mutations in patients who present with 2 consecutive unsuppressed VL in a resource-limited setting.In 10 nurse-led clinics in rural Lesotho children and adults on first-line ART for ≥6 months received a first routine VL. Those with plasma VL ≥80 copies/mL were enrolled in a prospective study, receiving enhanced adherence counseling (EAC) and a follow-up VL after 3 months. After a second unsuppressed VL genotypic resistance testing was performed. Viruses with major mutations against ≥2 drugs of the current regimen were classified as "resistant".A total of 1563 adults and 191 children received a first routine VL. Of the 138 adults and 53 children with unsuppressed VL (≥80 copies/mL), 165 (116 adults; 49 children) had a follow-up VL after EAC; 108 (74 adults; 34 children) remained unsuppressed and resistance testing was successful. Ninety of them fulfilled the WHO definition of treatment failure (both VL ≥1000 copies/mL); for another 18 both VL were unsuppressed but with <1000 copies/mL. The positive predictive value (PPV) for the WHO failure definition was 81.1% (73/90) for the presence of resistant virus. Among the 18 with VL levels between 80 and 1000 copies/mL, thereby classified as "non-failures", 17 (94.4%) harbored resistant viruses. Lowering the VL threshold from 1000 copies/mL to 80 copies/mL at both determinations had no negative influence on the PPV (83.3%; 90/108).The current WHO-definition misclassifies patients who harbor resistant virus at VL below 1000 c/mL as "nonfailing." Lowering the threshold to VL ≥80 copies/mL identifies a significantly higher number of patients with treatment-resistant virus and should be considered.
世界卫生组织（WHO）的抗逆转录病毒疗法（ART）指南将治疗失败定义为连续两次病毒载量（VL）≥1000拷贝/毫升。然而，几乎没有证据支持将1000拷贝作为定义治疗失败的最佳阈值。本研究的目的是在资源有限的环境中，评估WHO定义与连续两次未被抑制的VL患者中耐药突变存在情况之间的相关性。
在莱索托农村地区的10个由护士主导的诊所中，接受一线抗逆转录病毒治疗≥6个月的儿童和成人接受了首次常规病毒载量检测。血浆病毒载量≥80拷贝/毫升的患者被纳入一项前瞻性研究，接受强化依从性咨询（EAC），并在3个月后进行病毒载量随访。在第二次未被抑制的病毒载量检测后进行基因耐药性检测。对当前治疗方案中针对≥2种药物有主要突变的病毒被归类为“耐药”。
共有1563名成人和191名儿童接受了首次常规病毒载量检测。在138名成人和53名儿童的病毒载量未被抑制（≥80拷贝/毫升）的患者中，165名（116名成人；49名儿童）在接受EAC后进行了病毒载量随访；108名（74名成人；34名儿童）仍未被抑制，耐药性检测成功。其中90名符合WHO治疗失败的定义（两次病毒载量均≥1000拷贝/毫升）；另有18名患者两次病毒载量均未被抑制，但低于1000拷贝/毫升。WHO失败定义对耐药病毒存在情况的阳性预测值（PPV）为81.1%（73/90）。在18名病毒载量水平在80至1000拷贝/毫升之间、因此被归类为“未失败”的患者中，17名（94.4%）携带耐药病毒。将两次检测的病毒载量阈值从1000拷贝/毫升降至80拷贝/毫升对PPV没有负面影响（83.3%；90/108）。
当前的WHO定义将病毒载量低于1000拷贝/毫升但携带耐药病毒的患者错误地归类为“未失败”。将阈值降至病毒载量≥80拷贝/毫升可识别出数量显著更多的携带耐药病毒的患者，应予以考虑。
