澳大利亚监狱内丙型肝炎治疗即预防的评估（SToP-C）：一项前瞻性队列研究。
Evaluation of hepatitis C treatment-as-prevention within Australian prisons (SToP-C): a prospective cohort study.
机构信息
The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.
The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
出版信息
Lancet Gastroenterol Hepatol. 2021 Jul;6(7):533-546. doi: 10.1016/S2468-1253(21)00077-7. Epub 2021 May 7.
BACKGROUND
Limited empirical evidence exists for the effectiveness of hepatitis C virus (HCV) treatment-as-prevention. The Surveillance and Treatment of Prisoners with hepatitis C (SToP-C) study aimed to assess the effect of HCV treatment-as-prevention in the prison setting.
METHODS
SToP-C was a prospective study, including a before-and-after analysis, within a cohort of people incarcerated in two maximum-security prisons (male) and two medium-security prisons (one male, one female) in New South Wales, Australia. All prison inmates aged at least 18 years were eligible for enrolment. After HCV testing, participants were monitored for risk behaviours and HCV infection, among three sub-populations: uninfected (HCV antibody-negative); previously infected (HCV antibody-positive, HCV RNA-negative); and infected (HCV antibody and HCV RNA-positive). Uninfected participants were followed up every 3-6 months to detect HCV primary infection and previously infected participants were followed up every 3-6 months to detect re-infection. Participants with HCV infection were assessed for treatment, initially standard-of-care treatment (administered by prison health services) from 2014 to mid-2017, then direct-acting antiviral (DAA) treatment scale-up from mid-2017 onwards (12 weeks of sofosbuvir plus velpatasvir, administered through SToP-C). Participants were followed up until study closure in November, 2019. The primary study outcome was HCV incidence before and after DAA treatment scale-up among participants at risk of HCV primary infection or re-infection. This study is registered with ClinicalTrials.gov, NCT02064049.
FINDINGS
Between Oct 30, 2014, and Sept 30, 2019, 3691 participants were enrolled in the SToP-C study. 719 (19%) participants had detectable HCV RNA, 2240 (61%) were at risk of primary HCV infection, and 725 (20%) were at risk of re-infection at baseline. DAA treatment was initiated in 349 (70%) of 499 eligible participants during the treatment scale-up period. The HCV incidence analysis comprised 1643 participants at risk of HCV infection or re-infection during longitudinal follow-up (median age 33 years [IQR 27-42]; 1350 [82%] male). 487 (30%) of 1643 participants reported injecting drugs in prison. HCV incidence decreased from 8·31 per 100 person-years in the pre-treatment scale-up period to 4·35 per 100 person-years in the post-treatment scale-up period (incidence rate ratio [IRR] 0·52 [95% CI 0·36-0·78]; p=0·0007). The incidence of primary infection decreased from 6·64 per 100 person-years in the pre-treatment scale-up period to 2·85 per 100 person-years in the post-treatment scale-up period (IRR 0·43 [95% CI 0·25-0·74]; p=0·0019), whereas the incidence of re-infection decreased from 12·36 per 100 person-years to 7·27 per 100 person-years (0·59 [0·35-1·00]; p=0·050). Among participants reporting injecting drugs during their current imprisonment, the incidence of primary infection decreased from 39·08 per 100 person-years in the pre-treatment scale-up period to 14·03 per 100 person-years in the post-treatment scale-up period (IRR 0·36 [95% CI 0·16-0·80]; p=0·0091), and the incidence of re-infection decreased from 15·26 per 100 person-years to 9·34 per 100 person-years (0·61 [0·34-1·09]; p=0·093). The adjusted analysis (adjusted for age, Indigenous Australian ethnicity, duration of stay in prison, previous imprisonment, injecting drug use status, and prison site) indicated a significant reduction in the risk of HCV infection between the pre-DAA treatment scale-up and post-DAA treatment scale-up periods (adjusted hazard ratio 0·50 [95% CI 0·33-0·76]; p=0·0014).
INTERPRETATION
DAA treatment scale-up was associated with reduced HCV incidence in prison, indicative of a beneficial effect of HCV treatment-as-prevention in this setting. These findings support broad DAA treatment scale-up within incarcerated populations.
FUNDING
Australian National Health and Medical Research Council Partnership Project Grant and Gilead Sciences.
背景
目前仅有有限的证据表明丙型肝炎病毒（HCV）治疗即预防的有效性。监测和治疗囚犯中的丙型肝炎（SToP-C）研究旨在评估监狱环境中 HCV 治疗即预防的效果。
方法
SToP-C 是一项前瞻性研究，包括前后分析，纳入了澳大利亚新南威尔士州两个高度安全监狱（男性）和两个中度安全监狱（一个男性，一个女性）中被监禁的人群队列。所有年龄至少 18 岁的囚犯都有资格入组。在 HCV 检测后，根据三个亚人群监测风险行为和 HCV 感染：未感染（HCV 抗体阴性）；既往感染（HCV 抗体阳性，HCV RNA 阴性）；和感染（HCV 抗体和 HCV RNA 阳性）。未感染的参与者每 3-6 个月随访一次，以检测 HCV 原发性感染；而既往感染的参与者每 3-6 个月随访一次，以检测再感染。对 HCV 感染的参与者进行治疗评估，最初在 2014 年至 2017 年年中进行标准治疗（由监狱卫生服务提供），然后在 2017 年年中开始扩大直接作用抗病毒（DAA）治疗（12 周的索磷布韦加维帕他韦，通过 SToP-C 提供）。参与者一直随访到 2019 年 11 月研究结束。主要研究结果是在有 HCV 原发性感染或再感染风险的参与者中，在 DAA 治疗扩大阶段前后的 HCV 发病率。这项研究在 ClinicalTrials.gov 注册，NCT02064049。
结果
在 2014 年 10 月 30 日至 2019 年 9 月 30 日期间，有 3691 名参与者入组了 SToP-C 研究。719（19%）名参与者有可检测的 HCV RNA，2240（61%）名参与者有 HCV 原发性感染的风险，725（20%）名参与者有再感染的风险。在治疗扩大期间，有 499 名符合条件的参与者中有 349（70%）名开始接受 DAA 治疗。HCV 发病率分析包括在纵向随访中有 HCV 感染或再感染风险的 1643 名参与者（中位年龄 33 岁[IQR 27-42]；1350 名[82%]为男性）。1643 名参与者中有 487 名（30%）在监狱中注射毒品。在治疗扩大前阶段，HCV 发病率为每 100 人年 8.31 例，在治疗扩大后阶段为每 100 人年 4.35 例（发病率比[IRR]0.52[95%CI 0.36-0.78]；p=0.0007）。在治疗扩大前阶段，原发性感染的发病率为每 100 人年 6.64 例，在治疗扩大后阶段为每 100 人年 2.85 例（IRR 0.43[95%CI 0.25-0.74]；p=0.0019），而再感染的发病率从每 100 人年 12.36 例下降到每 100 人年 7.27 例（0.59[0.35-1.00]；p=0.050）。在目前监禁期间报告注射毒品的参与者中，原发性感染的发病率从治疗扩大前阶段的每 100 人年 39.08 例下降到治疗扩大后阶段的每 100 人年 14.03 例（IRR 0.36[95%CI 0.16-0.80]；p=0.0091），再感染的发病率从每 100 人年 15.26 例下降到每 100 人年 9.34 例（0.61[0.34-1.09]；p=0.093）。调整分析（调整了年龄、澳大利亚原住民种族、监禁时间、既往监禁、注射毒品使用状况和监狱地点）表明，在 DAA 治疗扩大前和扩大后期间，HCV 感染的风险显著降低（调整后的危险比 0.50[95%CI 0.33-0.76]；p=0.0014）。
解释
DAA 治疗扩大与监狱中 HCV 发病率降低相关，表明 HCV 治疗即预防在这种环境中具有有益效果。这些发现支持在被监禁人群中广泛扩大 DAA 治疗。
资金
澳大利亚国家卫生和医学研究委员会合作项目拨款和吉利德科学公司。
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