Adherence to antiretroviral therapy, virological response, and time to resistance in the Dakar cohort.
Adherence to antiretroviral therapy, virological response, and time to resistance in the Dakar cohort.
复制标题
达喀尔队列中抗逆转录病毒治疗的坚持、病毒学反应和耐药时间。
DOI：
10.1002/sim.3779
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发表时间：
2010
影响因子：
2
通讯作者：
DeGruttola,V
中科院分区：
文献类型：
--
作者：
Tournoud,M;Etard,JF;Ecochard,R;DeGruttola,V
1998年，塞内加尔启动了“获得抗逆转录病毒药物倡议”（ISAARV），成为最早提出获得抗逆转录病毒药物方案的非洲国家之一。本文的目的是研究任何首次耐药的时间，以及耐药时间的预测因子。我们提出了一个联合模型来研究坚持HAART治疗和病毒学反应对耐药突变时间的影响。采用logistic混合模型对时间依赖性依从性过程进行建模；并使用马尔可夫模型来研究病毒学反应。鉴于在粘附过程和病毒学应答中存在缺失数据，潜伏的粘附和病毒学状态随后被纳入到耐药时间模型的线性预测因子中。提出的抗性时间模型考虑了间隔审查数据以及零危险期，在此期间病毒复制非常低。贝叶斯方法用于适应缺失数据和预测。我们还提出了模型检验工具来研究模型的充分性。版权所有©2009 John Wiley & Sons， Ltd
In 1998, with the launch of the Senegalese Initiative for Antiretroviral Access (ISAARV), Senegal became one of the first African countries to propose an antiretroviral access program. Our objective in this paper is to study the time to any first drug resistance, as well as predictors of the time to resistance. We propose a joint model to study the effect of adherence to the HAART therapy, and virological response on the time to resistance mutations. A logistic mixed model is used to model the time‐dependent adherence process; and a Markov model is used to study the virological response. Given the presence of missing data in the adherence process and in the virological response, the latent adherence and virological states are then included in the linear predictor of the time to resistance model. The proposed time to resistance model takes into account interval‐censored data as well as null hazard periods, during which the viral replication is very low. A Bayesian approach is used for accommodating with missing data and for prediction. We also propose model checking tools to study model adequacy. Copyright © 2009 John Wiley & Sons, Ltd.