Parienti Jean-Jacques, Massari Véronique, Reliquet Véronique, Chaillot Fabien, Le Moal Gwenaël, Arvieux Cédric, Vabret Astrid, Verdon Renaud
INSERM U707, Epidémiologie, Systèmes d'informations, Modélisation, Paris, F-75012, France.
AIDS. 2007 Oct 18;21(16):2217-22. doi: 10.1097/QAD.0b013e3282eff388.
For optimal adherence, once-daily dosing is best. Whether this applies to antiretroviral therapy is unknown. We thus aimed to determine the effect of once-daily dosing on adherence to nevirapine.
A three-phase (3-month observational, 4-month randomized, 5-month interventional) open-label, clinical trial at four French academic medical centres during 2005-2006 among 62 chronically HIV-1-infected subjects with long-lasting viral suppression under a twice-a-day nevirapine-based antiretroviral combination.
Adherence was measured using electronic monitoring devices and validated by sequential plasma drug levels. Participants were randomly assigned to switch to nevirapine 400 mg once-daily (n = 31) or continue nevirapine 200 mg twice-a-day (n = 31). After the randomized phase, participants had an opportunity to choose their antiretroviral dosage. Primary outcome was the mean percentage of adherence.
Fifty-two patients qualified for electronic data analysis. During the randomized phase, the mean adherence rate was non-significantly superior by 0.5% in once-daily versus twice-a-day dosing (P = 0.68), adjusting for previous twice-a-day adherence rate (P < 0.0001). Once-daily group increased days without dose [odds ratio (OR) 1.7; 95% confidence interval (CI) 1.0, 2.8; P = 0.04], adjusting for previous drug interruptions (P < 0.0001). In the longitudinal analysis, once-daily dosing was significantly associated with at least two consecutive days without dose (OR 4.4; 95% CI 1.9, 10.3; P < 0.001).
Changing from twice to once-daily nevirapine does not improve adherence. Supporting continuous adherence to antiretroviral therapy in the 'once-a-day era' remains a challenge, even if more potent regimens can achieve viral suppression at lower adherence levels.
为实现最佳依从性，每日一次给药是最佳方式。但这是否适用于抗逆转录病毒疗法尚不清楚。因此，我们旨在确定每日一次给药对奈韦拉平依从性的影响。
2005年至2006年期间，在法国四个学术医学中心进行的一项三阶段（3个月观察期、4个月随机期、5个月干预期）开放标签临床试验，研究对象为62名长期接受基于奈韦拉平的每日两次抗逆转录病毒联合治疗且病毒得到长期抑制的慢性HIV-1感染者。
使用电子监测设备测量依从性，并通过连续血浆药物水平进行验证。参与者被随机分配改为每日一次服用400毫克奈韦拉平（n = 31）或继续每日两次服用200毫克奈韦拉平（n = 31）。在随机阶段结束后，参与者有机会选择他们的抗逆转录病毒药物剂量。主要结局是平均依从率。
52名患者符合电子数据分析条件。在随机阶段，调整先前的每日两次依从率后（P < 0.0001），每日一次给药的平均依从率比每日两次给药高0.5%，但差异无统计学意义（P = 0.68）。调整先前的药物中断情况后（P < 0.0001），每日一次给药组无剂量天数增加[比值比（OR）1.7；95%置信区间（CI）1.0，2.8；P = 0.04]。在纵向分析中，每日一次给药与至少连续两天无剂量显著相关（OR 4.4；95%CI 1.9，10.3；P < 0.001）。
从每日两次改为每日一次服用奈韦拉平并不能提高依从性。在“每日一次时代”，支持持续依从抗逆转录病毒疗法仍然是一项挑战，即使更有效的治疗方案可以在较低依从水平下实现病毒抑制。
