Chawana Tariro D, Gandhi Monica, Nathoo Kusum, Ngara Bernard, Louie Alexander, Horng Howard, Katzenstein David, Metcalfe John, Nhachi Charles F B
*Department of Clinical Pharmacology, University of Zimbabwe, Harare, Zimbabwe; †Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA; ‡Department of Paediatrics, University of Zimbabwe, Harare, Zimbabwe; §Department of Community Medicine, University of Zimbabwe, Harare, Zimbabwe; ‖Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA; and ¶Division of Pulmonary and Critical Care, Department of Medicine, University of California San Francisco, San Francisco, CA.
J Acquir Immune Defic Syndr. 2017 Sep 1;76(1):55-59. doi: 10.1097/QAI.0000000000001452.
Adequate antiretroviral exposure is crucial to 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 second-line antiretroviral treatment in Zimbabwe.
HIV-infected adolescents on atazanavir/ritonavir-based second-line treatment for ≥6 months with viral load (VL) >1000 copies/mL were randomized to either standard care (control) or standard care plus modified directly administered antiretroviral therapy (intervention). Questionnaires were administered; VL and hair samples were collected at baseline and after 90 days in each group. Viral suppression was defined as <1000 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 <2.35 ng/mg (lower interquartile range for those with virological suppression) defined a cutoff 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 (>2.35 ng/mg) hair concentrations. Participants with virological failure were more likely to have suboptimal atazanavir hair concentrations (RR = 7.2, 95% CI: 1 to 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 (2.35 ng/mg), above which virological suppression was likely, was defined for adolescents failing second-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.
充分的抗逆转录病毒暴露对于病毒学抑制至关重要。我们评估了在津巴布韦接受二线抗逆转录病毒治疗失败的HIV感染青少年中，阿扎那韦头发水平与自我报告的依从性、病毒学结果之间的关系，以及家庭式依从性干预的效果。
接受基于阿扎那韦/利托那韦的二线治疗≥6个月且病毒载量（VL）>1000拷贝/mL的HIV感染青少年被随机分为标准护理组（对照组）或标准护理加改良直接给药抗逆转录病毒治疗组（干预组）。进行问卷调查；在每组的基线和90天后收集VL和头发样本。病毒抑制定义为随访后<1000拷贝/mL。
招募了50名青少年（10 - 18岁）；23名（46%）被随机分配到干预组，27名（54%）被分配到对照组。阿扎那韦头发浓度<2.35 ng/mg（病毒学抑制者的下四分位数范围）定义了一个临界值，低于该临界值的大多数参与者经历了病毒学失败。男性（P = 0.03）、随访时的病毒学抑制（P = 0.013）、VL的更大降低（P = 0.006）以及前一个月自我报告依从性的变化（P = 0.031）与足够（>2.35 ng/mg）的头发浓度相关。病毒学失败的参与者更有可能阿扎那韦头发浓度不理想（RR = 7.2，95% CI：1至51，P = 0.049）。随访后两组之间阿扎那韦头发浓度没有差异。
对于在津巴布韦接受基于阿扎那韦/利托那韦的二线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），高于该阈值可能实现病毒学抑制。男性和更好的自我报告依从性与足够的阿扎那韦头发浓度相关。抗逆转录病毒头发浓度可能是青少年中一种有用的临床工具。
