Undiagnosed HIV infection remains the main driver of new HIV cases in Western countries. Emergency Departments (EDs) offer a key opportunity for detection. In 2020, Spanish emergency and infectious diseases societies recommended an opt-in strategy for targeted conditions for HIV testing in EDs. This study evaluates the efficacy of three strategies for targeted HIV testing. Twelve Spanish EDs, selected based on predefined structural criteria, assessed HIV testing from April to June 2024. Hospitals applied: no strategy (control, three EDs), an educational programme (strategy A, three EDs), strategy A plus preconfigured electronic orders (strategy B, three EDs) or strategy B plus electronic alerts in medical records (strategy C, three EDs). The impact on HIV testing was measured overall and by targeted condition, using absolute differences with 95% confidence intervals (CIs). Of the 612 909 ED visits, 210 039 occurred in control hospitals (1232 patients [0.59%] had targeted conditions), 172 806 in hospitals applying strategy A (1497 [0.87%]), 132 835 in strategy B hospitals (1761 [1.33%]) and 97 229 in hospitals applying strategy C (1269 [1.31%]). Testing rates were 0.16%, 0.38%, 1.17% and 2.16% in the control, and strategy A, B and C EDs., respectively. Among patients with targeted conditions, testing reached 13.1%, 22.9%, 30.7% and 78.1%. Compared to no strategy, testing increased by 0.22% (95% CI = 0.18-0.25) with strategy A, 0.79% (95% CI = 0.73-0.86) with B, and 0.98% (95% CI = 0.88-1.09) with C. In targeted conditions, testing rose by 9.8%, 7.8% and 47.5% for strategies A, B and C, respectively. All strategies improved testing in sexually transmitted infections (STI), meningitis/neurological syndromes and community-acquired pneumonia (CAP); strategy C also increased testing in herpes zoster (HZ) and post-exposure prophylaxis. All the strategies evaluated enhanced targeted HIV testing, especially strategy C (electronic alerts), which was associated with the highest testing rates observed, particularly in STI, CAP and HZ.
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