Atazanavir Concentration in Hair Is the Strongest Predictor of Outcomes on Antiretroviral Therapy
Atazanavir Concentration in Hair Is the Strongest Predictor of Outcomes on Antiretroviral Therapy
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DOI：
10.1093/cid/cir131
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发表时间：
2011-05-15
影响因子：
11.8
通讯作者：
Greenblatt, Ruth M.
中科院分区：
文献类型：
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作者：
Gandhi, Monica;Ameli, Niloufar;Greenblatt, Ruth M.
背景充分暴露于抗逆转录病毒药物对于维持持久的应答很重要，但评估暴露的方法（例如，询问依从性和单一血浆药物水平测量）有限。抗逆转录病毒药物的毛发浓度可以将依从性和药代动力学整合到一个单一的分析中。从妇女机构间艾滋病研究（WIHS）的参与者中收集了少量头发样本，WIHS是一个大型的人类免疫缺陷病毒（HIV）感染（和高危非感染）妇女队列。从2003年到2008年，我们纵向分析了报告接受阿扎那韦为基础的治疗的妇女阿扎那韦头发浓度。采用多变量随机效应logistic回归模型进行重复测量，以评估毛发药物水平与病毒学抑制（HIV RNA水平，< 80拷贝/mL）主要结局的相关性。424名WIHS参与者（51%为非洲裔美国人，31%为西班牙裔）为分析贡献了1443人次。在调整了年龄、种族、治疗经验、治疗前病毒载量、CD 4计数和艾滋病状态以及自我报告的依从性后，毛发水平是抑制的最强预测因子。头发抗逆转录病毒水平分类显示与抑制呈单调关系;阿扎那韦水平最高五分位数的妇女病毒抑制的优势比（OR）为59.8（95%置信比，29.0-123.2）。在既往有过依从性缺失的亚组中，毛发阿扎那韦浓度与病毒载量再抑制的相关性更强（OR，210.2 [95%CI，46.0-961.1]），毛发水平低（OR，132.8 [95%CI，26.5-666.0]），或可检测的病毒血症（OR，400.7 [95%CI，52.3-3069.7]）。在一个大型队列中，抗逆转录病毒头发水平超过了HIV治疗病毒学结果的任何其他预测因素。在无法测量病毒载量的情况下，头发中的低抗逆转录病毒暴露可能在失败之前触发干预措施或预示病毒学失败。监测头发抗逆转录病毒药物浓度可能有助于延长方案的持久性。
Background. Adequate exposure to antiretrovirals is important to maintain durable responses, but methods to assess exposure (eg, querying adherence and single plasma drug level measurements) are limited. Hair concentrations of antiretrovirals can integrate adherence and pharmacokinetics into a single assay.Methods. Small hair samples were collected from participants in the Women's Interagency HIV Study (WIHS), a large cohort of human immunodeficiency virus (HIV)-infected (and at-risk noninfected) women. From 2003 through 2008, we analyzed atazanavir hair concentrations longitudinally for women reporting receipt of atazanavir-based therapy. Multivariate random effects logistic regression models for repeated measures were used to estimate the association of hair drug levels with the primary outcome of virologic suppression (HIV RNA level, < 80 copies/mL).Results. 424 WIHS participants (51% African-American, 31% Hispanic) contributed 1443 person-visits to the analysis. After adjusting for age, race, treatment experience, pretreatment viral load, CD4 count and AIDS status, and self-reported adherence, hair levels were the strongest predictor of suppression. Categorized hair antiretroviral levels revealed a monotonic relationship to suppression; women with atazanavir levels in the highest quintile had odds ratios (ORs) of 59.8 (95% confidence ratio, 29.0-123.2) for virologic suppression. Hair atazanavir concentrations were even more strongly associated with resuppression of viral loads in subgroups in which there had been previous lapses in adherence (OR, 210.2 [95% CI, 46.0-961.1]), low hair levels (OR, 132.8 [95% CI, 26.5-666.0]), or detectable viremia (OR, 400.7 [95% CI, 52.3-3069.7]).Conclusions. Antiretroviral hair levels surpassed any other predictor of virologic outcomes to HIV treatment in a large cohort. Low antiretroviral exposure in hair may trigger interventions prior to failure or herald virologic failure in settings where measurement of viral loads is unavailable. Monitoring hair antiretroviral concentrations may be useful for prolonging regimen durability.