Cost-effectiveness of a smart pillbox intervention for adherence to oral HIV pre-exposure prophylaxis.

Despite proven oral pre-exposure prophylaxis (PrEP) efficacy, adherence barriers among men who have sex with men (MSM) persist. Economic viability of digital adherence tools in low- and middle-income countries (LMICs) requires validation. We assessed the 6-month within-trial cost-effectiveness of a digital intervention for real-time enhancement of oral PrEP adherence (DIRECT-PrEP) in China, from health system, multipayer, and societal perspectives. Costs were derived from hospital records, and effectiveness was evaluated using quality-adjusted life-years (QALYs) and PrEP-adherence days (PADs). Among 442 participants (247 intervention, 195 standard care), incremental costs per QALY gained for the smart pillbox intervention were $19,575.93 (health system), $19,656.66 (multipayer), and $19,844.42 (societal)-all below the cost-effectiveness threshold of three times per capita gross domestic product ($31,200). Costs per PAD gained were $30.46-$30.86, achieving >95% probability of cost-effectiveness at willingness-to-pay thresholds of $47.50-$48.50 per PAD. Notably, the intervention demonstrated greater cost-effectiveness per QALY among participants stratified as more socially vulnerable ($16,259.77-$16,490.41) compared with those classified as less socially vulnerable ($23,514.83-$23,834.38). These results establish the smart-pillbox digital intervention as a cost-effective strategy for oral PrEP adherence within primary healthcare settings in LMICs, particularly when prioritizing more socially vulnerable populations, though long-term scalability requires further validation.