Defining a Cutoff for Atazanavir in Hair Samples Associated With Virological Failure Among Adolescents Failing Second-Line Antiretroviral Treatment.
Defining a Cutoff for Atazanavir in Hair Samples Associated With Virological Failure Among Adolescents Failing Second-Line Antiretroviral Treatment.
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DOI：
10.1097/qai.0000000000001452
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发表时间：
2017-09-01
期刊：
影响因子：
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通讯作者：
Adolescent Treatment Failure (ATF) study team
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文献类型：
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作者：
Chawana TD;Gandhi M;Nathoo K;Ngara B;Louie A;Horng H;Katzenstein D;Metcalfe J;Nhachi CFB;Adolescent Treatment Failure (ATF) study team
充分的抗逆转录病毒暴露对于病毒学抑制至关重要。我们评估了阿扎那韦毛发水平与自我报告的依从性、病毒学结果之间的关系，以及在津巴布韦二线抗逆转录病毒治疗失败的HIV感染青少年中进行家庭依从性干预的效果。接受阿扎那韦/利托那韦二线治疗≥6个月且病毒载量（VL）> 1，000拷贝/ml的HIV感染青少年被随机分配至标准治疗组（对照组）或标准治疗加改良的直接给药抗逆转录病毒治疗（mDAART）组（干预组）。在基线和90天后，在每组中采集VL和毛发样本。病毒抑制定义为随访后<1，000拷贝/ml。入组了50名青少年（10-18岁）; 23名（46%）被随机分配到干预组，27名（54%）被随机分配到对照组。阿扎那韦毛发浓度<2.35 ng/mg（病毒学抑制者的四分位数范围较低）定义了一个截止值，低于该截止值，大多数参与者发生病毒学失败。男性（p=0.03）、随访时的病毒学抑制（p=0.013）、VL的较大降低（p=0.006）和前一个月平均自我报告依从性的变化（p=0.031）与足够（> 2.35 ng/mg）的毛发浓度相关。病毒学失败的受试者更有可能出现次优阿扎那韦毛发浓度（RR=7.2，95% CI=1-51，p=0.049）。随访后两组阿扎那韦毛发浓度无差异。在津巴布韦，对于二线阿扎那韦/利托那韦抗逆转录病毒治疗失败的青少年，定义了头发中阿扎那韦浓度的阈值（2.35 ng/mg），高于该阈值可能产生病毒学抑制。男性和更好的自我报告的依从性与足够的阿扎那韦毛发浓度相关。抗逆转录病毒头发浓度可以作为一个有用的临床工具，在青少年。
Adequate antiretroviral exposure is crucial for virological suppression. We assessed the relationship between atazanavir hair levels with self-reported adherence, virological outcomes, and the effect of a home-based adherence intervention in HIV-infected adolescents failing 2nd-line antiretroviral treatment in Zimbabwe. HIV-infected adolescents on atazanavir/ritonavir-based 2nd-line treatment for ≥6 months with viral load (VL) >1,000 copies/ml were randomised to either standard care (control) or standard care plus modified directly administered antiretroviral therapy (mDAART) (intervention). Questionnaires were administered; VL and hair samples were collected at baseline and after 90 days in each group. Viral suppression was defined as <1,000 copies/ml after follow-up. Fifty adolescents (10–18 years) were enrolled; 23(46%) were randomized to intervention and 27(54%) to control. Atazanavir hair concentration <2.35ng/mg (lower inter-quartile range for those with virological suppression) defined a cut-off below which most participants experienced virological failure. Male sex (p=0.03), virological suppression at follow-up (p=0.013), greater reduction in VL (p=0.006) and change in average self-reported adherence over the previous month (p=0.031) were associated with adequate (>2.35ng/mg) hair concentrations. Participants with virological failure were more likely to have sub-optimal atazanavir hair concentrations (RR=7.2, 95% CI=1–51, p=0.049). There were no differences in atazanavir hair concentration between the arms after follow-up. A threshold of atazanavir concentrations in hair (2.35ng/mg), above which virological suppression was likely, was defined for adolescents failing 2nd line atazanavir/ritonavir-based ART in Zimbabwe. Male sex and better self-reported adherence were associated with adequate atazanavir hair concentrations. Antiretroviral hair concentrations may serve as a useful clinical tool among adolescents.