Explaining variability in the relationship between antiretroviral adherence and HIV mutation accumulation
Explaining variability in the relationship between antiretroviral adherence and HIV mutation accumulation
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DOI：
10.1093/jac/dkl386
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发表时间：
2006-11-01
影响因子：
5.2
通讯作者：
Justice, A. C.
中科院分区：
文献类型：
--
作者：
Braithwaite, R. S.;Shechter, S.;Justice, A. C.
目的：确定抗逆转录病毒药物依从性与耐药性积累之间的关系对药物设计和治疗具有重要意义。依从性干预措施的评估。我们的目的是解释在这种关系中观察到的异质性。方法：我们首先进行了一项系统综述，以找到描述依从性和预后之间关系的已发表报告。阻力。然后，我们使用经过验证的计算机模拟来模拟这些报告中的患者群体，探索个体患者特征（年龄、CD4、病毒载量、先前抗逆转录病毒经历）变化对粘附-耐药（a -r）曲线形状的影响。结果：共检索到493篇文献，其中3篇文献包含相关的原始资料，2篇文献有足够的随访纳入（HOMER和REACH队列）。在模拟HOMER时，a - r曲线有一个高峰，累积突变的风险比（HR）大大增加。部分依从性与完全依从性相比（模拟，HR 2.9； HOMER, HR 2.7）。当模拟REACH时，a - r曲线有一个浅峰，在部分粘附时积累突变的风险略有增加（模拟，HR 1.2； REACH, HR 1.4）。这种异质性主要归因于队列间抗逆转录病毒治疗经验的差异。结论：我们的计算机模拟能够解释观察到的A-R曲线的大部分异质性。
Objectives: Determining the relationship between antiretroviral adherence and resistance accumulation is important for the design and. evaluation of adherence interventions. Our objective was to explain heterogeneity observed in this relationship.Methods: We first conducted a systematic review to locate published reports describing the relationship between adherence and. resistance. We then used a validated computer simulation to simulate the patient populations in these reports, exploring the impact of changes in individual patient characteristics (age, CD4, viral load, prior antiretroviral experience) on the shape of the adherence-resistance (A-R) curve.Results: The search identified 493 titles, of which 3 contained relevant primary data and 2 had sufficient follow-up for inclusion (HOMER and REACH cohorts). When simulating HOMER, the A-R curve had a high peak with a greatly increased hazard ratio (HR) of accumulating mutations at. partial compared to complete adherence (simulation, HR 2.9; HOMER, HR 2.7). When simulating REACH, the A-R curve had a shallow peak with a slightly increased hazard of accumulating mutations at partial adherence (simulation, HR 1.2; REACH, HR 1.4). This heterogeneity was primarily attributable to differences in antiretroviral experience between the cohorts.Conclusions: Our computer simulation was able to explain much of the heterogeneity in observed A-R curves.