Abstract
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). 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. 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. clinicaltrials.gov NCT03519425.
Highlights
Despite being a leading infectious cause of adult mortality worldwide [1], tuberculosis (TB) remains challenging to diagnose, especially in low-resource settings [2]
Sputum smear microscopy has low sensitivity and is resource intensive [8]; Xpert— more sensitive, especially for HIV–positive people [9,10]—is costly, and throughput is constrained by unit capacity [11]; lateral flow urine lipoarabinomannan assay (LF-LAM) is not currently recommended for HIV–negative people or HIV–positive outpatients without advanced immunosuppression [12]; and sputum mycobacterial culture remains costly, slow, and inaccessible to most primary clinics
WHO has recently recommended that DCXR-CAD can be used for TB screening [18], but the impact on patient outcomes is unknown. In this three-arm pragmatic randomised trial conducted in primary care in urban Blantyre, Malawi, we investigated whether a universal HIV testing and linkage to antiretroviral therapy (ART) intervention—either alone or combined with DCXR-CAD and subsequent sputum Xpert confirmation—could improve the timeliness and completeness of HIV and TB diagnosis and treatment
Summary
Despite being a leading infectious cause of adult mortality worldwide [1], tuberculosis (TB) remains challenging to diagnose, especially in low-resource settings [2]. Only a small percentage of clinic attenders successfully complete the TB screening cascade due to limited health worker numbers, high numbers of patient with symptoms of TB overwhelming testing capacity, and low availability and high cost of diagnostics [7]. Sputum smear microscopy has low sensitivity and is resource intensive [8]; Xpert— more sensitive, especially for HIV–positive people [9,10]—is costly, and throughput is constrained by unit capacity [11]; lateral flow urine lipoarabinomannan assay (LF-LAM) is not currently recommended for HIV–negative people or HIV–positive outpatients without advanced immunosuppression [12]; and sputum mycobacterial culture remains costly, slow, and inaccessible to most primary clinics. Offering newer TB diagnostics such as Xpert to all adult primary clinic attenders with symptoms of TB (which can approach 60% [7]) could rapidly overwhelm clinic testing capacity and health systems’ budgets. We investigated costs and yield from systematic HIV-TB screening, including computeraided digital chest X-ray (DCXR-CAD)
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