Liu Honghu, Miller Loren G, Hays Ron D, Golin Carol E, Wu Tongtong, Wenger Neil S, Kaplan Andrew H
Division of General Internal Medicine and Health Services Research, Department of Medicine, University of California-Los Angeles (UCLA), 911 Broxton Plaza, Los Angeles, CA 90095-1736, USA.
J Acquir Immune Defic Syndr. 2006 Mar;41(3):315-22. doi: 10.1097/01.qai.0000197071.77482.6e.
Adherence to antiretroviral medications is critical to achieving HIV viral suppression. Studies have been limited to cross-sectional analyses using measures that reflect only the percentage of prescribed doses taken (percent adherence), however. The contribution of dose timing and other factors to achieving virologic suppression has received less scrutiny.
In a longitudinal study, we collected detailed adherence information using multiple tools along with demographic, clinical, social-behavioral, and virologic measures. Subjects were followed for 48 weeks. Percent adherence, dose-timing, genotypic sensitivity, and virologic outcomes were collected every 4 weeks. Repeated measures mixed effects models (RMMEMs) were used to model the relation between virologic outcomes and adherence as well as genotypic sensitivity and others.
Of the 141 subjects, mean percent adherence was 73% with a downward trend. Viral load (VL) dropped significantly (P = 0.01) over time. RMMEMs revealed that higher genotypic sensitivity, higher percent adherence, lower baseline VL, longer inclusion in the study, earlier HIV stage, and smaller dose-timing error were significantly associated with lower VL. In multivariate modeling, a 0.50 increase in the genotypic sensitivity score, a 10% increase in adherence, and a decrease of 3 hours of dose-timing error were associated with a decrease in log10 HIV RNA at 48 weeks of 0.69, 0.54, and 0.48, respectively (P < 0.05 for each).
Long-term viral suppression requires consistent and high percent adherence accompanied by optimal interdose intervals. Efforts to improve viral outcomes should address not only missed doses but excessive variation in dose timing and prevention of adherence decline over time. Preventing the development and transmission of resistant variants is also critically important.
坚持服用抗逆转录病毒药物对于实现HIV病毒抑制至关重要。然而，此前的研究仅限于使用仅反映所服用规定剂量百分比（服药依从率）的指标进行横断面分析。剂量时间安排和其他因素对实现病毒学抑制的贡献受到的审查较少。
在一项纵向研究中，我们使用多种工具收集了详细的依从性信息以及人口统计学、临床、社会行为和病毒学指标。对受试者进行了48周的随访。每4周收集一次服药依从率、剂量时间安排、基因型敏感性和病毒学结果。使用重复测量混合效应模型（RMMEMs）来模拟病毒学结果与依从性以及基因型敏感性和其他因素之间的关系。
在141名受试者中，平均服药依从率为73%，且呈下降趋势。随着时间的推移，病毒载量（VL）显著下降（P = 0.01）。RMMEMs显示，更高的基因型敏感性、更高的服药依从率、更低的基线VL、纳入研究的时间更长、HIV分期更早以及更小的剂量时间误差与更低的VL显著相关。在多变量建模中，基因型敏感性评分增加0.50、依从性增加10%以及剂量时间误差减少3小时分别与48周时log10 HIV RNA下降0.69（P < 0.05）、0.54（P < 0.05）和0.48（P < 0.05）相关。
长期的病毒抑制需要持续且高的服药依从率以及最佳的给药间隔时间。改善病毒学结果的努力不仅应解决漏服剂量的问题，还应解决剂量时间安排的过度变化以及防止依从性随时间下降的问题。预防耐药变异株的产生和传播也至关重要。
