Department of Infectious Disease Epidemiology, Imperial College, Faculty of Medicine, London, UK.
AIDS. 2012 Sep 24;26(15):1953-9. doi: 10.1097/QAD.0b013e32835722bd.
To quantify the performance of existing first-line and second-line combination antiretroviral therapy (cART) regimens on patient's clinical outcomes in the Netherlands using ATHENA data and to evaluate the potential for new drug regimens to improve patient's clinical outcomes using a data-based mathematical model.
We analysed data from 3995 patients from the Dutch ATHENA national observational cohort between 2000 and 2010. We quantified the main drug-related reasons for switching from first-line and second-line cART, classified as toxicity, simplification/new medication becoming available, virological failure, or other reasons. We developed a deterministic model describing HIV infection and treatment in the Netherlands parameterized on the basis of these data. The model simulated how a new drug regimen, with either improved toxicity or virological failure profile, could impact on patient's clinical outcomes.
The main reason for switching current first-line and second-line regimens was toxicity, accounting for around 50% of switching from first-line and from second-line cART. The model found that a new drug regimen with increased tolerability profile could have the highest potential impact on patient's outcomes, especially as a first-line treatment. A new first-line drug regimen with improved tolerability could increase the time patients spend on first-line cART, decrease their risk of switching from first-line cART and thus simplify patient management.
New drug regimens with improved toxicity profiles could have the greatest impact on patient outcomes and simplify patient management in the Netherlands.
利用 ATHENA 数据量化荷兰现有一线和二线联合抗逆转录病毒治疗(cART)方案对患者临床结局的疗效,并通过基于数据的数学模型评估新药物方案改善患者临床结局的潜力。
我们分析了 2000 年至 2010 年间来自荷兰 ATHENA 国家观察队列的 3995 名患者的数据。我们量化了从一线和二线 cART 转换的主要与药物相关的原因,分为毒性、简化/新药物可用、病毒学失败或其他原因。我们开发了一个确定性模型,根据这些数据对荷兰的 HIV 感染和治疗进行参数化描述。该模型模拟了具有改善毒性或病毒学失败特征的新药物方案如何影响患者的临床结局。
转换当前一线和二线方案的主要原因是毒性,约占一线和二线 cART 转换的 50%。该模型发现,具有更高耐受性特征的新药物方案可能对患者结局产生最大影响,特别是作为一线治疗。具有改善耐受性特征的新一线药物方案可以增加患者接受一线 cART 的时间,降低其从一线 cART 转换的风险,从而简化患者管理。
具有改善毒性特征的新药物方案可能对荷兰患者的结局产生最大影响,并简化患者管理。