High levels of adherence do not prevent accumulation of HIV drug resistance mutations
High levels of adherence do not prevent accumulation of HIV drug resistance mutations
复制标题
DOI：
10.1097/00002030-200309050-00011
复制
发表时间：
2003-09-05
期刊：
影响因子：
3.8
通讯作者：
Moss, A
中科院分区：
文献类型：
--
作者：
Bangsberg, DR;Charlebois, ED;Moss, A
目的：通过测量治疗时间、病毒学抑制和不同依从性水平下新的耐药突变积累率，评估抗逆转录病毒药物耐药发展与依从性的关系。方法：在hiv阳性的城市贫困个体的前瞻性队列中，通过在参与者通常居住的地方进行未通知的药丸计数来测量依从性。在治疗方案稳定且病毒血症可检出的个体（bbb50拷贝/ml）中，获得了间隔6个月的2个基因型耐药试验（G1和G2）。主要耐药结局是在G1和G2之间的6个月内发生的新的HIV抗逆转录病毒耐药突变的数量。结果：148例患者中，高依从性与较长的治疗时间（P < 0.0001）和病毒抑制（P < 0.0001）密切相关。在57例接受稳定治疗的血浆病毒载量为50拷贝/ml的患者中，新的耐药突变的积累与先前治疗的持续时间（P = 0.03）和药丸数依从性（P = 0.002）呈正相关。假设完全抑制个体（< 50拷贝/ml）不产生耐药性，估计23%的耐药发生在依从性最高的五分之一（92 - 100%），超过50%的耐药突变发生在依从性最高的两个五分之一（79 - 100%）。结论：高依从性下病毒抑制率的增加与病毒血症患者耐药率的增加相平衡。异常高的依从性并不能防止人群的耐药性。(C) 2003利平科特·威廉姆斯·威尔金斯。
Objectives: To assess the relationship between development of antiretroviral drug resistance and adherence by measured treatment duration, virologic suppression, and the rate of accumulating new drug resistance mutations at different levels of adherence.Methods: Adherence was measured with unannounced pill counts performed at the participant's usual place of residence in a prospective cohort of HIV-positive urban poor individuals. Two genotypic resistance tests separated by 6 months (G1 and G2) were obtained in individuals on a stable regimen and with detectable viremia (> 50 copies/ml). The primary resistance outcome was the number of new HIV antiretroviral drug resistance mutations occurring over the 6 months between G1 and G2.Results: High levels of adherence were closely associated with greater time on treatment (P < 0.0001) and viral suppression (P < 0.0001) in 148 individuals. In a subset of 57 patients with a plasma viral load > 50 copies/ml on stable therapy, the accumulation of new drug resistance mutations was positively associated with the duration of prior treatment (P = 0.03) and pill count adherence (P = 0.002). Assuming fully suppressed individuals (< 50 copies/ml) do not develop resistance, it was estimated that 23% of all drug resistance occurs in the top quintile of adherence (92 - 100%), and over 50% of all drug resistance mutations occur in the top two quintiles of adherence (79 - 100%).Conclusion: Increasing rates of viral suppression at high levels of adherence is balanced by increasing rates of drug resistance among viremic patients. Exceptionally high levels of adherence will not prevent population levels of drug resistance. (C) 2003 Lippincott Williams Wilkins.