Choice of time horizon critical in estimating costs and effects of changes to HIV programmes

Background
Uganda changed its antiretroviral therapy guidelines in 2014, increasing the CD4 threshold for antiretroviral therapy initiation from 350 cells/μl to 500 cells/μl. We investigate what effect this change in policy is likely to have on HIV incidence, morbidity, and programme costs, and estimate the cost-effectiveness of the change over different time horizons.
Methods
We used a complex individual-based model of HIV transmission and antiretroviral therapy scale-up in Uganda. 100 model fits were generated by fitting the model to 51 demographic, sexual behaviour, and epidemiological calibration targets, varying 96 input parameters, using history matching with model emulation. An additional 19 cost and disability weight parameters were varied during the analysis of the model results. For each model fit, the model was run to 2030, with and without the change in threshold to 500 cells/μl.
Results
The change in threshold led to a 9.7% (90% plausible range: 4.3%-15.0%) reduction in incidence in 2030, and averted 278,944 (118,452–502,790) DALYs, at a total cost of $28M (-$142M to +$195M). The cost per disability adjusted life year (DALY) averted fell over time, from $3238 (-$125 to +$29,969) in 2014 to $100 (-$499 to +$785) in 2030. The change in threshold was cost-effective (cost <3×Uganda’s per capita GDP per DALY averted) by 2018, and highly cost-effective (cost
Conclusions
Model results suggest that the change in threshold is unlikely to have been cost-effective to date, but is likely to be highly cost-effective in Uganda by 2030. The time horizon needs to be chosen carefully when projecting intervention effects. Large amounts of uncertainty in our results demonstrates the need to comprehensively incorporate uncertainties in model parameterisation.

研究背景
乌干达于2014年更新了抗反转录病毒治疗（antiretroviral therapy, ART）指南，将抗反转录病毒治疗启动时的CD4阈值从350 cells/μl上调至500 cells/μl。本研究旨在探讨该政策调整对人类免疫缺陷病毒（Human Immunodeficiency Virus, HIV）新发感染率、疾病负担及项目成本的潜在影响，并估算不同时间跨度下该政策调整的成本效益。
方法
本研究采用乌干达地区HIV传播与抗反转录病毒治疗扩面的复杂个体模型（individual-based model, IBM）。通过基于模型仿真的历史匹配方法，将模型拟合至51项人口统计学、性行为及流行病学校准目标，同时调整96个输入参数，共生成100组模型拟合结果。在模型结果分析阶段，额外调整了19项成本与伤残权重（disability weight, DW）参数。针对每一组模型拟合结果，均在保留与取消CD4阈值上调至500 cells/μl两种场景下，将模型运行至2030年。
结果
2030年时，CD4阈值上调可使HIV新发感染率降低9.7%（90%可信区间：4.3%~15.0%），共计挽救278944（118452~502790）个伤残调整寿命年（Disability-Adjusted Life Years, DALYs），总成本为2800万美元（区间：-1.42亿美元至+1.95亿美元）。每挽救1个伤残调整寿命年（DALY）所需的成本随时间推移逐渐下降，从2014年的3238美元（区间：-125美元至+29969美元）降至2030年的100美元（区间：-499美元至+785美元）。截至2018年，该阈值调整已具备成本效益（每挽救1个DALY的成本低于乌干达人均国内生产总值的3倍），且高度具备成本效益（成本
结论
模型结果显示，截至目前该CD4阈值调整未必具备成本效益，但至2030年在乌干达地区将具备极高成本效益。在预测干预措施的效果时，需谨慎选择时间跨度。本研究结果中存在的大量不确定性，凸显了在模型参数化过程中全面纳入不确定性因素的必要性。