Early treatment of acute hepatitis C infection is cost-effective in HIV-infected men-who-have-sex-with-men

Background
Treatment of hepatitis C virus infections (HCV) with direct acting antivirals (DAA) can prevent new infections since cured individuals cannot transmit HCV. However, as DAAs are expensive, many countries defer treatment to advances stages of fibrosis, which results in ongoing transmission. We assessed the epidemiological impact and cost-effectiveness of treatment initiation in different stages of infection in the Netherlands where the epidemic is mainly concentrated among HIV-infected MSMs.
Methods
We calibrated a deterministic mathematical model to the Dutch HCV epidemic among HIV-infected MSM to compare three different DAA treatment scenarios: 1) immediate treatment, 2) treatment delayed to chronic infection allowing spontaneous clearance to occur, 3) treatment delayed until F2 fibrosis stage. All scenarios are simulated from 2015 onwards. Total costs, quality adjusted life years (QALY), incremental cost-effectiveness ratios (ICERs), and epidemiological impact were calculated from a providers perspective over a lifetime horizon. We used a DAA price of €35,000 and 3% discounting rates for cost and QALYs.
Results
Immediate DAA treatment lowers the incidence from 1.2/100 person-years to 0.2/100 person-years (interquartile range 0.1–0.2) and the prevalence from 5.0/100 person-years to 0.5/100 person-years (0.4–0.6) after 20 years. Delayed treatment awaiting spontaneous clearance will result in a similar reduction. However, further delayed treatment to F2 will increases the incidence and prevalence. Earlier treatment will cost society €68.3 and €75.1 million over a lifetime for immediate and awaiting until the chronic stage, respectively. The cost will increase if treatment is further delayed until F2 to €98.4 million. Immediate treatment will prevent 7070 new infections and gains 3419 (3019–3854) QALYs compared to F2 treatment resulting in a cost saving ICER. Treatment in the chronic stage is however dominated.
Conclusions
Early DAA treatment for HIV-infected MSM is an excellent and sustainable tool to meet the WHO goal of eliminating HCV in 2030.

研究背景
使用直接抗病毒药物（direct acting antivirals, DAA）治疗丙型肝炎病毒（hepatitis C virus, HCV）感染可预防新发感染，因为感染者治愈后不再具有HCV传播能力。然而，由于直接抗病毒药物价格高昂，许多国家将治疗推迟至纤维化进展阶段，导致病毒持续传播。本研究针对主要在HIV感染男男性行为者（men who have sex with men, MSM）中流行的荷兰HCV疫情，评估了在感染不同阶段启动治疗的流行病学影响与成本效果。
研究方法
我们针对荷兰HIV感染男男性行为者人群中的HCV疫情构建确定性数学模型并进行校准，以对比三种不同的DAA治疗方案：1）即刻启动治疗；2）推迟至慢性感染阶段（允许自发清除发生）再进行治疗；3）推迟至F2期纤维化阶段再治疗。所有方案均自2015年起开展模拟。本研究从医疗机构视角，在终生时间跨度内计算了总治疗成本、质量调整生命年（quality adjusted life years, QALY）、增量成本效果比（incremental cost-effectiveness ratios, ICERs）以及流行病学影响。本研究采用的DAA单价为35000欧元，并对成本与QALY采用3%的贴现率。
研究结果
即刻启动DAA治疗可在20年后将发病率从1.2/100人年降至0.2/100人年（四分位间距0.1~0.2），将患病率从5.0/100人年降至0.5/100人年（0.4~0.6）。等待自发清除的延迟治疗方案可实现类似的疫情降幅。但进一步推迟治疗至F2期纤维化阶段则会升高发病率与患病率。与F2期治疗方案相比，即刻启动治疗与等待至慢性感染阶段再治疗的终生社会总成本分别为6830万欧元与7510万欧元；若进一步推迟至F2期治疗，总成本将升至9840万欧元。即刻启动治疗可避免7070例新发感染，较F2期治疗多获得3419（3019~3854）个质量调整生命年，且增量成本效果比为成本节约型。而慢性期启动治疗的方案则被即刻治疗方案所主导。
研究结论
针对HIV感染男男性行为者的早期DAA治疗，是实现世界卫生组织（World Health Organization, WHO）2030年消除HCV目标的优质且可持续的干预手段。