University of Florida, Gainesville, Florida, USA.
Pharmacoeconomics. 2010;28(11):1025-39. doi: 10.2165/11535540-000000000-00000.
Abacavir sulfate (abacavir) is associated with a hypersensitivity reaction (HSR) that affects 5-8% of patients. While serious complications are rare, failure to identify it, or abacavir re-challenge following HSR, can be fatal. Genetic screening for HLA-B*5701 can identify patients who are likely to experience an HSR and reduces the incidence of the reaction.
We assessed the intrinsic and practical value, from the US healthcare system perspective, of prospective HLA-B*5701 screening among a population of antiretroviral-naive patients without elevated risk factors for cardiovascular disease, plasma HIV RNA >100,000 copies/mL, or pre-existing renal insufficiency.
Two approaches were used to evaluate the costs and benefits of prospective screening. First, the efficiency of HLA-B5701 screening compared with no screening prior to abacavir initiation (intrinsic value of screening) was evaluated using a 60-day decision-tree model. Next, the practical value of screening was assessed using a lifetime discrete-event simulation model that compared HLA-B5701 screening prior to abacavir use versus initiation with a tenofovir-containing regimen. Screening-effectiveness parameters were taken from an open-label trial that incorporated screening prior to abacavir initiation and other published studies. Treatment efficacy was derived from clinical trials. Modelling assumptions, costs ($US, year 2007 values) and other parameters were derived from published sources, primary data analysis and expert opinion. Multiple one-way sensitivity and scenario analyses were performed to assess parameter uncertainty. The primary outcome measure for the short-term screening versus no screening analysis was cost per patient. For the long-term analysis, outcomes were presented as QALYs. Costs and effects were discounted at 3% per year.
Over the first 60 days of treatment, prospective screening prior to abacavir initiation cost an additional $US17 per patient and avoided 537 HSRs per 10,000 patients. The per-patient cost of screening was sensitive to the cost of the genetic test, HSR costs and screening performance. In the lifetime model, screening-informed abacavir use was more effective and less costly than initiation with a tenofovir-containing regimen in the base case and in sensitivity analyses.
Our results suggest that prospective HLA-B*5701 screening prior to abacavir initiation produces cost savings and should become a standard component of HIV care.
硫酸阿巴卡韦（abacavir）可引起过敏反应（HSR），影响 5-8%的患者。虽然严重并发症很少见，但如果未能识别出该反应，或在 HSR 后重新使用阿巴卡韦，可能会致命。HLA-B*5701 的基因筛查可识别出可能发生 HSR 的患者，并降低反应发生率。
我们从美国医疗保健系统的角度评估了在没有心血管疾病高危因素、血浆 HIV RNA>100,000 拷贝/ml 或预先存在的肾功能不全的抗逆转录病毒初治患者中进行前瞻性 HLA-B*5701 筛查的内在和实际价值。
采用两种方法评估前瞻性筛查的成本和效益。首先，使用 60 天决策树模型评估 HLA-B5701 筛查与阿巴卡韦起始前不筛查（筛查的内在价值）相比的效率。其次，使用终生离散事件模拟模型评估筛查的实际价值，该模型比较了阿巴卡韦使用前进行 HLA-B5701 筛查与使用含替诺福韦方案起始治疗的情况。筛查效果参数来自于一项纳入阿巴卡韦起始前筛查的开放性标签试验和其他已发表的研究。治疗效果来自临床试验。模型假设、成本（2007 年美元价值）和其他参数来自已发表的资料、主要数据分析和专家意见。进行了多次单因素敏感性和情景分析，以评估参数不确定性。短期筛查与不筛查分析的主要结果测量是每位患者的成本。对于长期分析，结果以 QALYs 表示。成本和效果按每年 3%贴现。
在治疗的头 60 天内，阿巴卡韦起始前进行前瞻性筛查每位患者额外花费 17 美元，可避免每 10,000 名患者发生 537 例 HSR。筛查的每位患者成本对基因检测成本、HSR 成本和筛查性能敏感。在终生模型中，与使用含替诺福韦方案起始治疗相比，基于 HLA-B*5701 信息的阿巴卡韦使用在基本情况和敏感性分析中更有效且成本更低。
我们的研究结果表明，在阿巴卡韦起始前进行前瞻性 HLA-B*5701 筛查可节省成本，应成为 HIV 护理的标准组成部分。
