BACKGROUND Suboptimal tuberculosis (TB) diagnostics and HIV contribute to the high global burden of TB. We investigated costs and yield from systematic HIV-TB screening, including computer-aided digital chest X-ray (DCXR-CAD). METHODS AND FINDINGS In this open, three-arm randomised trial, adults (≥18 years) with cough attending acute primary services in Malawi were randomised (1:1:1) to standard of care (SOC); oral HIV testing (HIV screening) and linkage to care; or HIV testing and linkage to care plus DCXR-CAD with sputum Xpert for high CAD4TBv5 scores (HIV-TB screening). Participants and study staff were not blinded to intervention allocation, but investigator blinding was maintained until final analysis. The primary outcome was time to TB treatment. Secondary outcomes included proportion with same-day TB treatment; prevalence of undiagnosed/untreated bacteriologically confirmed TB on day 56; and undiagnosed/untreated HIV. Analysis was done on an intention-to-treat basis. Cost-effectiveness analysis used a health-provider perspective. Between 15 November 2018 and 27 November 2019, 8,236 were screened for eligibility, with 473, 492, and 497 randomly allocated to SOC, HIV, and HIV-TB screening arms; 53 (11%), 52 (9%), and 47 (9%) were lost to follow-up, respectively. At 56 days, TB treatment had been started in 5 (1.1%) SOC, 8 (1.6%) HIV screening, and 15 (3.0%) HIV-TB screening participants. Median (IQR) time to TB treatment was 11 (6.5 to 38), 6 (1 to 22), and 1 (0 to 3) days (hazard ratio for HIV-TB versus SOC: 2.86, 1.04 to 7.87), with same-day treatment of 0/5 (0%) SOC, 1/8 (12.5%) HIV, and 6/15 (40.0%) HIV-TB screening arm TB patients (p = 0.03). At day 56, 2 SOC (0.5%), 4 HIV (1.0%), and 2 HIV-TB (0.5%) participants had undiagnosed microbiologically confirmed TB. HIV screening reduced the proportion with undiagnosed or untreated HIV from 10 (2.7%) in the SOC arm to 2 (0.5%) in the HIV screening arm (risk ratio [RR]: 0.18, 0.04 to 0.83), and 1 (0.2%) in the HIV-TB screening arm (RR: 0.09, 0.01 to 0.71). Incremental costs were US$3.58 and US$19.92 per participant screened for HIV and HIV-TB; the probability of cost-effectiveness at a US$1,200/quality-adjusted life year (QALY) threshold was 83.9% and 0%. Main limitations were the lower than anticipated prevalence of TB and short participant follow-up period; cost and quality of life benefits of this screening approach may accrue over a longer time horizon. CONCLUSIONS DCXR-CAD with universal HIV screening significantly increased the timeliness and completeness of HIV and TB diagnosis. If implemented at scale, this has potential to rapidly and efficiently improve TB and HIV diagnosis and treatment. TRIAL REGISTRATION clinicaltrials.gov NCT03519425.

中文翻译：

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马拉维成人咳嗽患者的结核病计算机辅助 X 射线筛查和 HIV 检测（PROSPECT 研究）：一项随机试验和成本效益分析。

背景 不理想的结核病 (TB) 诊断和 HIV 导致全球结核病的高负担。我们调查了系统性 HIV-TB 筛查的成本和收益，包括计算机辅助数字胸部 X 光检查 (DCXR-CAD)。方法和结果 在这项开放的三组随机试验中，在马拉维接受急性初级服务的咳嗽成人（≥18 岁）被随机分配（1:1:1）接受标准治疗（SOC）；口腔 HIV 检测（HIV 筛查）和与护理的联系；或 HIV 检测和与护理的联系加上 DCXR-CAD 和痰 Xpert 以获得高 CAD4TBv5 分数（HIV-TB 筛查）。参与者和研究人员未对干预分配设盲，但研究者设盲状态一直持续到最终分析。主要结果是接受结核病治疗的时间。次要结果包括当天接受结核病治疗的比例；第 56 天未诊断/未治疗的细菌学确诊结核病的患病率；和未确诊/未治疗的艾滋病毒。分析是在意向治疗的基础上进行的。成本效益分析使用了健康提供者的观点。2018 年 11 月 15 日至 2019 年 11 月 27 日期间，对 8,236 人进行了资格筛查，其中 473、492 和 497 人随机分配到 SOC、HIV 和 HIV-TB 筛查组；分别有 53 人 (11%)、52 人 (9%) 和 47 人 (9%) 失访。在 56 天时，5 名 (1.1%) SOC、8 名 (1.6%) HIV 筛查参与者和 15 名 (3.0%) HIV-TB 筛查参与者开始接受结核病治疗。接受结核病治疗的中位 (IQR) 时间为 11（6.5 至 38）、6（1 至 22）和 1（0 至 3）天（HIV-TB 与 SOC 的风险比：2.86、1.04 至 7.87），与-天治疗 0/5 (0%) SOC、1/8 (12.5%) HIV 和 6/15 (40.0%) HIV-TB 筛查臂结核病患者 (p = 0.03)。在第 56 天，2 名 SOC (0.5%)、4 名 HIV (1.0%) 和 2 名 HIV-TB (0.5%) 参与者未确诊为微生物学确诊的结核病。HIV 筛查将未确诊或未治疗的 HIV 比例从 SOC 组的 10 (2.7%) 降低到 HIV 筛查组的 2 (0.5%)（风险比 [RR]：0.18，0.04 至 0.83）和 1 (0.2%) ) 在 HIV-TB 筛查组中（RR：0.09，0.01 至 0.71）。每名接受 HIV 和 HIV-TB 筛查的参与者的增量成本分别为 3.58 美元和 19.92 美元；1,200 美元/质量调整生命年 (QALY) 阈值的成本效益概率分别为 83.9% 和 0%。主要局限性是结核病患病率低于预期和参与者随访期较短；这种筛查方法的成本和生活质量益处可能会在更长的时间范围内累积。结论 DCXR-CAD 与普遍的 HIV 筛查显着提高了 HIV 和 TB 诊断的及时性和完整性。如果大规模实施，这有可能快速有效地改善结核病和艾滋病毒的诊断和治疗。试用注册 clinicaltrials.gov NCT03519425。