Dual environmental threat of ozone and cold spells amplifying AIDS-related mortality in China

People living with HIV/AIDS (PLWH) represent a uniquely vulnerable population in the context of global environmental change. While the independent health risks of air pollution and extreme temperatures are recognized, the concept of a dual environmental threat—specifically, the combined impact of ozone (O 3 ) and cold-spell day frequency (CS)—on AIDS-related mortality remains unexplored. We constructed a two-decade (2001–2020), population-based open cohort study that included 28,140 participants in Hubei Province, China. Annual O 3 exposure was estimated using a high-resolution gridded dataset, while CS indicators were derived from the ERA5-LAND reanalysis data. The selected CS definition was a daily mean temperature below the county-specific 10th percentile for at least two consecutive days. Time-varying Cox proportional hazard models were performed to estimate the impacts of O 3 and CS on AIDS-related deaths. Sensitivity analyses included exposure misclassification correction and placebo tests to ensure robustness. During 132,353.9 person-years of follow-up, 2,023 AIDS-related deaths were recorded. Each interquartile range increase in O 3 (8.8 ppb) and cold-spell day frequency (17 days) was associated with higher risks of AIDS-related mortality, with HRs of 1.15 (95% CI: 1.08, 1.23) and 1.18 (95% CI: 1.10, 1.26), respectively. Critically, a strong synergistic interaction was identified. The joint exposure resulted in a multiplicative effect, with an interaction HR of 1.89 (95% CIs: 1.58, 2.26) and a relative excess risk due to interaction of 0.63 (95% CIs: 0.48, 0.78), indicating that the combined risk far exceeded the sum of individual risks. Long-term O 3 exposure and more frequent cold-spell days were associated with higher AIDS-related mortality among PLWH in Hubei Province, and their joint exposure was associated with additional risk beyond their individual associations. These findings highlight the importance of considering multiple environmental stressors in the health management of PLWH.