Ozone and Cold Spells Together Sharply Raise AIDS-Related Death Risk in China

People living with HIV have long battled a virus that quietly erodes the immune system, but a new study from China suggests the environment around them may be an equally formidable adversary. A two-decade, population-based cohort study conducted in Hubei Province has found that long-term exposure to ground-level ozone and to cold spells—periods of unusually low temperatures lasting at least two consecutive days—each independently raises the risk of AIDS-related death. More striking still, when the two stressors occur together, their combined effect on mortality is far greater than the sum of their individual risks, a statistical pattern known as synergistic interaction.

The research, published in BMC Public Health, followed 28,140 people living with HIV/AIDS in Hubei Province between 2001 and 2020. The investigators assembled an open cohort, meaning participants could enter and exit the study at different points across the twenty-year window, and accumulated more than 132,000 person-years of observation. During that time, 2,023 AIDS-related deaths were recorded. By linking each participant’s residential location to high-resolution environmental data, the team could estimate the annual ozone concentration and the frequency of cold-spell days that each individual experienced, and then ask how those exposures shaped survival.

The technical machinery behind the exposure assessment is worth unpacking, because it represents one of the study’s key strengths. Annual ozone exposure was estimated using a high-resolution gridded dataset, which allows researchers to assign plausible pollution values even to people living in areas without nearby monitoring stations. Cold-spell indicators, meanwhile, were derived from ERA5-LAND, a state-of-the-art atmospheric reanalysis product that blends satellite observations with numerical weather modeling to produce a continuous record of surface conditions. The team defined a cold-spell day as a day on which the mean temperature fell below the county-specific 10th percentile for at least two consecutive days—a definition that adapts to local climate norms rather than imposing a single national threshold, an important consideration in a province that spans both subtropical lowlands and cooler mountainous terrain.

To translate these exposures into risk estimates, the researchers employed time-varying Cox proportional hazard models, the workhorse of survival analysis. These models estimate how a given exposure changes the instantaneous rate of death over time while allowing exposure levels to change across the follow-up period—essential in a study spanning twenty years of fluctuating pollution and weather. The results were consistent and sobering. Each interquartile range increase in ozone concentration, equivalent to 8.8 parts per billion, was associated with a 15 percent higher risk of AIDS-related mortality, with a hazard ratio of 1.15 and a 95 percent confidence interval of 1.08 to 1.23. Each interquartile range increase in cold-spell day frequency—17 additional cold-spell days per year—was associated with an 18 percent higher risk, with a hazard ratio of 1.18 and a confidence interval of 1.10 to 1.26.

The headline finding, however, lies in the interaction between the two exposures. When the researchers modeled ozone and cold spells jointly, they found a multiplicative rather than merely additive effect. The interaction hazard ratio was 1.89, with a 95 percent confidence interval of 1.58 to 2.26, and the relative excess risk due to interaction—a standard epidemiological measure of synergy—was 0.63, with a confidence interval of 0.48 to 0.78. In practical terms, this means that people exposed to both elevated ozone and frequent cold spells faced a mortality risk that substantially exceeded what would be predicted by simply adding the two individual hazards together. The combined threat was not just double trouble; it was a genuinely amplified danger.

Why might these two environmental stressors interact so powerfully in a population whose immune systems are already compromised? The authors’ findings point to the biology of people living with HIV/AIDS, a group the study describes as uniquely vulnerable in the context of global environmental change. Ozone is a potent oxidant that damages the respiratory epithelium, triggers systemic inflammation, and impairs lung function—burdens that a weakened immune system is poorly equipped to absorb. Cold stress, for its part, increases physiological strain, elevates blood pressure, and can suppress immune responses further, while also increasing susceptibility to respiratory infections. When both stressors coincide, the inflammatory and immunological toll may compound in ways that push a fragile physiological balance past its breaking point, accelerating progression to AIDS-related death.

The study’s robustness was tested through a battery of sensitivity analyses, including corrections for exposure misclassification and placebo tests designed to confirm that the observed associations were not artifacts of the modeling choices. The fact that the core results survived these checks lends weight to the conclusion that the ozone and cold-spell effects are real rather than statistical noise. The retrospective design was approved by the Institutional Review Board of Wuhan Jinyintan Hospital, and because all patient information was fully de-identified and anonymized, the requirement for informed consent was waived. The work drew on the HIV/AIDS Comprehensive Response Information Management System, a surveillance infrastructure that the authors credit for making such a large, long-duration cohort possible, and was supported by the Natural Science Foundation of Hubei Province.

The implications reach well beyond Hubei. Globally, nearly forty million people are living with HIV, and although antiretroviral therapy has transformed the disease into a manageable chronic condition, mortality among people living with HIV remains elevated compared with the general population, particularly in regions where environmental hazards are intense and healthcare access uneven. If air pollution and extreme temperatures can amplify AIDS-related deaths to the degree documented here, then climate change—which is expected to increase the frequency and severity of temperature extremes in many regions while ozone chemistry responds to a warming atmosphere—could quietly undermine hard-won gains in HIV survival. The study’s authors argue that their findings highlight the importance of considering multiple environmental stressors in the health management of people living with HIV/AIDS, rather than evaluating each hazard in isolation.

For public health authorities, the message is actionable. Health management programs for people living with HIV could incorporate environmental risk into routine care: warning systems for cold spells, guidance on reducing exposure during high-ozone episodes, and prioritization of vulnerable patients for interventions such as improved housing insulation or indoor air filtration. The dual-threat framework also offers a template for future research. Most environmental epidemiology has examined single pollutants or single temperature extremes, yet real-world exposures arrive in combination. The strong synergy documented in this cohort suggests that single-exposure studies may systematically underestimate the true health burden of environmental change on immunocompromised populations.

There are, of course, limits to what any observational study can establish. The analysis captures associations across a large cohort over two decades, and the sensitivity analyses strengthen confidence, but individual-level behavioral factors, treatment adherence, and clinical variables may still shape the observed patterns in ways that population-level models cannot fully disentangle. Nonetheless, the scale of the cohort, the length of follow-up, the rigor of the exposure assessment, and the clarity of the interaction signal make this one of the most compelling demonstrations to date that environmental stressors can act synergistically on mortality in people living with HIV. As the planet warms and air quality remains a persistent challenge in many rapidly developing regions, the study stands as a warning that the environments in which immunocompromised people live are not a backdrop to their health but an active force within it—and one that public health systems are only beginning to measure.

Subject of Research: Combined effects of ozone exposure and cold spells on AIDS-related mortality among people living with HIV in China

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

Article References: Zhao, D., Zhang, F., Zheng, W., Feng, Y., Zhang, W., Liu, Y., Ruan, L., Zhu, W., & Tang, H. (2026). Dual environmental threat of ozone and cold spells amplifying AIDS-related mortality in China. BMC Public Health. https://doi.org/10.1186/s12889-026-29824-6

Image Credits: AI Generated

DOI: 10.1186/s12889-026-29824-6

Keywords: ozone, cold spells, HIV, AIDS, mortality, air pollution, climate change, environmental health, synergistic interaction, Cox proportional hazards, Hubei Province, public health