High rates of virological failure and drug resistance in perinatally HIV-1-infected children and adolescents receiving lifelong antiretroviral therapy in routine clinics in Togo
High rates of virological failure and drug resistance in perinatally HIV-1-infected children and adolescents receiving lifelong antiretroviral therapy in routine clinics in Togo
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DOI：
10.7448/ias.19.1.20683
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发表时间：
2016-04-27
影响因子：
6
通讯作者：
Peeters, Martine
中科院分区：
文献类型：
--
作者：
Salou, Mounerou;Dagnra, Anoumou Y.;Peeters, Martine
在过去十年中，抗逆转录病毒治疗（ART）得到了扩大，但与成人相比，感染艾滋病毒的儿童接受抗逆转录病毒治疗的可能性较小。此外，儿童和青少年比成人更容易受到病毒学失败（VF）和耐药性出现的影响。在这项研究中，我们确定了在多哥接受抗逆转录病毒治疗的围产期感染hiv -1的儿童和青少年的病毒学结果。方法：2014年6月至9月，对所有接受抗逆转录病毒治疗至少12个月的儿童和青少年进行常规随访，并建议进行HIV病毒载量（VL）检测。血浆HIV-1 VL采用m2000 RealTime HIV-1检测（Abbott Molecular, Des Plaines， IL， USA）。所有VL浓度为1000拷贝/ml的样品均进行基因型耐药检测。结果与讨论：283例围产期感染hiv -1的儿童和青少年中，167例（59%）为青少年，116例（41%）为儿童。抗逆转录病毒治疗的中位持续时间为48个月（四分位数范围：28至68个月）。228例（80.6%），目前的ART组合包括两种核苷类逆转录酶抑制剂（齐多夫定和拉米夫定）和一种非核苷类逆转录酶抑制剂（奈韦拉平或依非韦伦）。只有28例（9.9%）采用了基于蛋白酶抑制剂（PI）的方案。VL低于检出限（40拷贝/ml）的102例（36%），在40 ~ 1000拷贝/ml之间的35例（12.4%），高于1000拷贝/ml的146例（51.6%）。基因型耐药检测成功125/146例（85.6%）；110/125（88.0%）对NRTIs和NNRTIs均耐药，1/125（0.8%）对NRTIs仅耐药，4/125（3.2%）对NNRTIs仅耐药，3个病毒对逆转录酶和pi耐药。总体而言，86%（108/125）经历VF并成功进行基因分型的儿童和青少年，相当于至少38%的研究人群，要么没有有效的抗逆转录病毒治疗，要么在目前的抗逆转录病毒治疗方案中只有一种有效的药物。结论：我们的研究为围产期感染hiv -1的儿童和青少年提供了终身抗逆转录病毒治疗的病毒学结果的重要信息，这些儿童和青少年仍然接受抗逆转录病毒治疗，并继续到抗逆转录病毒诊所进行随访。在资源有限的国家，扩大和监测儿童终身抗逆转录病毒治疗的实际情况可产生显著的长期结果，并表明儿科抗逆转录病毒治疗得不到足够的重视。
Introduction: Antiretroviral treatment (ART) has been scaled up over the last decade but compared to adults, children living with HIV are less likely to receive ART. Moreover, children and adolescents are more vulnerable than adults to virological failure (VF) and emergence of drug resistance. In this study we determined virological outcome in perinatally HIV-1-infected children and adolescents receiving ART in Togo.Methods: HIV viral load (VL) testing was consecutively proposed to all children and adolescents who were on ART for at least 12 months when attending HIV healthcare services for their routine follow-up visit (June to September 2014). Plasma HIV-1 VL was measured using the m2000 RealTime HIV-1 assay (Abbott Molecular, Des Plaines, IL, USA). Genotypic drug resistance was done for all samples with VL > 1000 copies/ml.Results and discussion: Among 283 perinatally HIV-1-infected children and adolescents included, 167 (59%) were adolescents and 116 (41%) were children. The median duration on ART was 48 months (interquartile range: 28 to 68 months). For 228 (80.6%), the current ART combination consisted of two nucleoside reverse transcriptase inhibitors (NRTIs) (zidovudine and lamivudine) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) (nevirapine or efavirenz). Only 28 (9.9%) were on a protease inhibitor (PI)-based regimen. VL was below the detection limit (i.e. 40 copies/ml) for 102 (36%), between 40 and 1000 copies/ml for 35 (12.4%) and above 1000 copies/ml for 146 (51.6%). Genotypic drug-resistance testing was successful for 125/146 (85.6%); 110/125 (88.0%) were resistant to both NRTIs and NNRTIs, 1/125 (0.8%) to NRTIs only, 4/125 (3.2%) to NNRTIs only and three harboured viruses resistant to reverse transcriptase and PIs. Overall, 86% (108/125) of children and adolescents experiencing VF and successfully genotyped, corresponding thus to at least 38% of the study population, had either no effective ART or had only a single effective drug in their current ART regimen.Conclusions: Our study provided important information on virological outcome on lifelong ART in perinatally HIV-1-infected children and adolescents who were still on ART and continued to attend antiretroviral (ARV) clinics for follow-up visits. Actual conditions for scaling up and monitoring lifelong ART in children in resource-limited countries can have dramatic long-term outcomes and illustrate that paediatric ART receives inadequate attention.