The Climate Change Burden on Immune Health: Are Persons Living with HIV More at Risk?

Abstract

Climate change poses one of the most significant modern threats to overall human health,especially for vulnerable populations including persons living with HIV (PLWH). In this perspective, we specifically explore the concept of immune resilience in human health and how climate change phenomena - including extreme weather events, food insecurity, pollution, and emerging diseases - may exacerbate immune dysfunction and comorbidities faced by PLWH and hinder access to HIV treatment and prevention services. Multidisciplinary, collaborative efforts are urgently needed to quantify these impacts, develop mitigation strategies, and strengthen policies and funding to bolster immune resilience for PLWH in the face of accelerating climate change.

Extrinsic and intrinsic stimuli shape the immune response and impact disease prevention, infection, and treatment. Collectively, the modulation of this experience can be referred to as immune resilience (IR) and defined as the capacity for the immune system to maintain appropriate responses to antigen exposure while minimizing deleterious inflammation and the ability to rapidly return to baseline homeostatic conditions^1,2 (Fig. 1). In brief, Auhuja et al.¹ describe IR scoring based on immune health grade (IHG), I to IV, and immunocompetence (IC)/inflammation (IF), low/high, scores. IC and IF are scored by surrogate survival associated signatures (SAS) and mortal associated signatures (MAS), respectively. The environment is an overwhelmingly influential extrinsic stimuli to IR, and by extension climate change inevitably will have an impact on immune modulation. Anthropogenic climate change resulting in rising temperatures and increased extreme weather events pose significant risks to global public health such as water-, food-, and vector-borne diseases, flooding, and pollutant exposure. Each of these factors affects the human immune system in complex ways, presenting unparalleled health challenges, which demand interdisciplinary collaborations for innovative solutions. Understanding human IR to climate change requires recognizing the contribution of environmental risk factors on specific diseases, social and geographic impacts on health outcomes, and the effects of individual pollutants or climate change-related stimuli on immune health. In this perspective piece, we explore the complex intersection of climate change, social determinants of health (SDOH), and the immune system in persons living with HIV (PLWH). We examine the effects of extreme weather events (EWE), food insecurity, pollution, and climate-related diseases on the prevention of, therapeutics for, and comorbidities associated with HIV/AIDS. We identify how these factors may affect immune function and susceptibility to HIV, and add perspective on the ability to effectively manage the global HIV/AIDS epidemic as climate change expands. We further urge action to prioritize understanding the impacts of climate change on immune health as a global public health concern and identify strategies for intervention.

FIG. 1.

Classification of clinical measures to determine immune health grade, and assessment of optimal, suboptimal, or non-optimal immune resilience. Immune resilience (IR) is defined by the combination of immune health grade (IHG) and immunocompetence (IC) and inflammation (IF) transcriptional profiles as described by Auhuja et al.¹ IC and IF signatures are measured via survival associated signatures (SAS) and mortality associated signatures (MAS), respectively.¹ The continuum of IR ranges from optimal IR of IGH-I and IC^high-IF^low to nonoptimal IR of IGH-II to-IV and IC^low-IF^high.

How Do Atmospheric and Environmental Exposures Influenced by Climate Change Impact Human Health?

Climate change, predominantly fueled by anthropogenic emissions,³ influences stratospheric ozone layers, solar UV radiation, and interconnected atmospheric conditions (temperature, precipitation, clouds, and strength of wind)⁴ with consequences for human health including materials used in key infrastructure (e.g., deterioration of construction adhesives, wool fabrics, and solar technologies).⁵ More intimately, climate change also directly threatens individuals’ immune health. Factors like carbon dioxide emissions can enhance allergen abundance and skew immune function toward heightened reactivity to antigens.⁶ Exposures such as air pollution, heat, wildfires, and biodiversity loss can impair the immune system’s ability to prevent a response against a particular antigen, increasing risks of autoimmune diseases, allergies, and metabolic disorders.⁷ It stands to reason that the global health impacts of climate change will include influences on the HIV/AIDS epidemic. Indeed, the consequences of climate change, including record-breaking temperatures and EWE, could lead to an increase of 11–16 million HIV cases in sub-Saharan Africa by 2050, and episodes of drought in particular can significantly affect HIV prevalence and treatment adherence.⁸ Populations in sub-Saharan Africa and Southeast Asia face heightened risks from climate change owing to their dependence on subsistence farming for economic stability and food security.⁹ We have previously outlined how these vulnerable populations, as well as minority populations in more economically secure nations, disproportionately face the burden of HIV and its interaction with climate change impacts.¹⁰ With this knowledge, the critical need to address the complex interconnectedness of climate change and HIV in order to mitigate the catastrophic effects on vulnerable populations becomes glaringly apparent.

In What Ways Will Climate Change Phenomena Exacerbate Comorbidities and Immune Dysfunction That People Living with HIV Already Face?

Recent assessments caution how climate change will exacerbate comorbidities associated with HIV. Climate transformations can induce chemical modifications influencing immunogenic proteins, while air pollutants act as adjuvants misleading immune defenses, and projections show expanded allergy disease burden as anthropogenic emissions drive changes in aeroallergen exposure.⁶ Droughts, deteriorating air quality as pollutants migrate in higher concentrations, and increasing temperatures related to ozone production will contribute to incidences of respiratory conditions to which PLWH are already prone,¹¹ emphasizing the importance of addressing this issue.¹² Exposure to UV radiation has been linked to inhibited antigen presentation, release of immunosuppressive cytokines, and damage to DNA, which can ultimately impact the generation of B and T cells, cells which are fundamentally cruicial to the immune system.^13–16 In general, higher ambient UV radiation and temperatures may combine to hinder the vaccine immune response and increase infection incidence, and increases in ozone pollution and pollen count driven by emissions present rising concerns for respiratory and allergic conditions.⁶ Furthermore, recent evidence has shown that climate change-induced heat stress can exacerbate inflammation and compromise immune function,^12,17 a possibility of particular concern for PLWH who often present chronic immune activation and inflammation even despite antiretroviral therapy (ART).¹⁸ Although optimal IR has been associated with lower HIV viral load during early infection, nonoptimal IR metrics have been associated with an increased risk of HIV acquisition.¹ Such immune impairment leaves those in developing regions with minimal capacity to buffer additional climate disruptions especially vulnerable to infection.

How Might Climate Change-induced Malnutrition and Migration Caused by Food Insecurity Increase Impacts of Immune Resilience and Affect Overall Mortality in Low-income Regions with High HIV Prevalence?

Other critical considerations are the interconnections that exist between migration driven by climate change impacts, high-risk behaviors, and HIV transmission dynamics. Changes in temperature and precipitation negatively affect crop production,⁹ whereas variations in pricing and damage to roads and shops hamper food infrastructure and access. In general, malnutrition impacts the immune system via epigenetic alterations which affect gene expression, leading to compromised T cell function and subsequent impairment of the body to defend itself from pathogens.¹⁹ Although vaccinations have historically been a method of supplementing loss of immunity in malnourished individuals, there is concern as to whether some vaccines will elicit decreased seroprotection and efficacy among undernourished children.²⁰ Undernutrition associated with climate change is projected to increase moderate stunting by 1%–29% and severe stunting by up to 62% among children in Africa and South Asia by 2050, which will dampen immune function and disproportionately increase risks for overall and disease-specific mortality in low-income regions.²¹ Malnutrition-induced immunodeficiency increases infection risk and severity and dampens responsiveness to vaccines for diseases to which PLWH are more vulnerable (i.e., tuberculosis),²² threatening individuals throughout their lifespan. The myriad issues arising from food insecurity can increase the possibility of migration, which, in turn, has an impact HIV transmission, new coinfections, and access to health care.

How is Climate Change Enabling the Geographic Expansion of Vector-borne, Water-borne, and Fungal Diseases that Pose Heightened Risks During HIV Coinfection?

Vector-borne, water-borne, and fungal diseases will expand their geographic range due to climate change, which could pose increased health challenges for PLWH.⁹ The burden of these diseases worsens during coinfection with HIV, owing to differences in overall immune health, and thus are critical factors to consider as they may dampen basal IR and immune health recovery. In addition, the transmission of novel viruses such as SARS-CoV-2 and their effect on public health infrastructure may be influenced by climate change, as poor air quality increases the severity of COVID-19 health outcomes,⁵ and climate change can impact the distribution and population density of animal vectors such as bats.⁹ Climate change and the spread of HIV/AIDS in many parts of Africa have created a cycle of declining food security, poor harvests, and reduced incomes, driving impoverished households affected by HIV/AIDS to increasingly depend on bushmeat (including rodents, nonhuman primates, reptiles, amphibians, and bats) as a low-cost yet nutritious food source to compensate for micronutrient deficiencies that frequently undermine immune function in people living with HIV/AIDS; studies demonstrate that in afflicted households, both adults and children are significantly more likely to consume bushmeat to meet their dietary needs compared with nonafflicted households.²³ Humans involved in the acquisition of bushmeat are at an increased risk for spillover of zoonotic pathogens, which contribute to emerging infectious diseases and threaten global public health, with outbreaks of Ebola, HIV, and SARS already linked to bushmeat activities.^24,25 In addition, phenological shifts in some animal species represent incomplete adaptive responses to climate change, imposing an evolutionary load that threatens species' persistence.²⁶ Current obstacles to predicting evolutionary adaptations to climate change could be benefited by studying diverse animal models, expanding functional genomic resources for nonmodel species, and integrating evolutionary experiments with omics data.²⁷

To What Extent do Climate Change-driven EWE Threaten Health Care Infrastructure and the Delivery of HIV Treatment Services in Resource-limited Settings?

Beyond direct immune pressures, climate change-related drought, flooding, food insecurity, migration, and transportation network disruptions may disproportionally impact health care and access to basic services for PLWH. Climate change-driven EWE threats to health care infrastructure in resource-limited settings⁹ could exacerbate the global epidemiology of HIV, as increasing surface temperatures lead to a surge in EWE, which damage housing, communication centers, hospitals, and transportation methods, diverting resources away from disease treatment and prevention. A growing body of literature has documented the intricate links between EWE driven by climate change and the ability to provide preventative care against HIV/AIDS. Recent publications regarding the impact of heat on health care infrastructure in low- or middle-income countries indicate that heat itself poses an enormous risk to various operations, as increased energy use puts pressure on vulnerable grids, rising heat challenges the cool storage and transport of temperature-sensitive medical equipment (i.e., vaccines) and damages equipment, and surges in patients threaten hospital capacity.^28–30 Loss of access to potable water through either drought or contamination poses a multifaceted threat by hindering testing programs, complicating ART adherence, and influencing sexual behaviors, thus increasing HIV prevalence through complex interactions with economic conditions, livelihoods, and various contextual factors.^31–33 As climate change-derived disruptions increase the incidence of HIV infection, it stands to reason that the availability of resources for treating PLHW will decline. When public health infrastructure is disturbed by EWE, effective provision of HIV/AIDS services to impacted communities can become extremely challenging, as evidenced by the 2009 Namibia floodings that damaged over 30 government health facilities, caused 41 health facilities and 179 outreach points to become inaccessible, and resulted in 23% of PLWH in the affected region reporting missed medication.³⁴ Indeed, EWE frequently disrupt health care utilization at the local level, as the negative impact of EWE on transportation and health care facilities hinders access to care for PLWH.³⁵ Food insecurity driven by climate-induced disruptions in transportation and agriculture also negatively impacts ART adherence,³⁶ an issue amplified by worsened side effects when taking ART without food and the prioritization of food over medication.³⁷ At the national level, improved coordination across agriculture, health, and transportation ministries is key for adaptation and maximization of resources and effectiveness, with cross-disciplinary international partnerships focusing on underlying social vulnerabilities in these regions being particularly promising approaches.³⁸ Strategies to help vulnerable communities adapt to the negative health impacts of climate change should prioritize education and sustainable agricultural technologies like solar irrigation and agroforestry in heavily affected rural areas.^39,40 Climate change adaptation will also need to address climate-related infectious diseases like dengue, malaria, or cholera coinfection with HIV through community education on their interactions, distribution of preventive measures like bed nets, and maintenance of sanitary sources of food, water, and soil.^41–44 Although each of these infrastructure considerations are more broadly indicative of challenges to health care, they should be considered within the context of IR given their basal impact across the lifespan, which presents obstacles to meaningful protective interventions.

What Collaborative, Multidisciplinary Efforts are Needed to Quantify Climate Impacts, Develop Mitigation Strategies, and Strengthen Policies/Funding to Improve Immune Resilience for PLWH in the Face of Climate Change?

We consider these issues a call to action to improve the IR of PLWH to minimize the impacts of climate change. The wide-ranging impacts of atmospheric conditions and environmental exposures underscore the urgent need to understand and mitigate the detrimental effects of climate change on IR. Climate change is a global issue, but its impacts are disproportionately felt by PLWH and those affected by societal disparities. In this aspect, climate change and the HIV pandemic are undeniably interconnected. As climate change threatens to undermine the progress made in global HIV/AIDS management, it becomes increasingly essential to integrate climate resilience into international health agendas, such as the Sustainable Development Goals outlined by the United Nations.⁴⁵ The World Health Organization has also identified several areas of focus for strategies to mitigate the health impacts of climate change, including reduction of carbon emissions, establishment of climate-resilient and environmentally sustainable health systems, and collaboration between health agencies, global experts, and civil society to raise awareness, conduct monitoring, and provide international support.⁴⁶ The inclusion of climate resilience strategies in the global HIV/AIDS response can help protect the progress that has been made in combatting the epidemic, ensuring that PLWH continue to receive the necessary care and support.⁹ By quantifying the impacts of climate change on IR more effectively, we can target specific challenges and compose mitigation strategies, take preventative measures, and strengthen access to care that will improve immune health. Investigators across disciplines must strive to exchange research, foster meaningful connections, and explore actionable solutions to bridge the gap between science and advocacy. Given the scope of the intersecting issues outlined herein, evidence-based interventions must be tailored to address climate-sensitive diseases such as HIV at multiple levels, including urban planning, water management, and educational campaigns.⁴⁷ We stress the critical need for sustained funding and policy discussions to address the adverse impact of climate change on immune health by developing and implementing innovative solutions. Suggestions for action by certain stakeholder groups are outlined in Table 1. With the collective efforts of researchers, policymakers, and the community at large, we can strive towards a healthier, more resilient future for all.

Table 1.

Suggested Items of Action for Various Stakeholder Groups to Successfully Implement Interventions for Climate Change-related Immune Health Issues, with a Particular Focus on Persons Living with HIV (PLWH)

Stakeholders	Interventions
Funders/donors	Identify and support organizations which prioritize the prevention of and response to environmental issues, particularly those with a focus on racial and economic justice.
Policy makers	Implement policies which manage diseases of public health importance and are sensitive to climate issues (e.g., disease surveillance, treatment facilities, educational programs).
Industry	Develop and promote medical therapeutics, medications, and vaccines that are more stable to circumvent climate change-induced disruptions to supply chains.
Epidemiologists	Monitor and report on continuation of care (e.g., clinical visits, medication continuation, laboratory testing) among PLWH, with a particular focus on the potential impacts of climate change on the immune resilience of PLWH.
Immunologists	Conduct investigations which further elucidate the impact of climate change on immune resilience at the cellular level, particularly within PLWH. In addition, refine efforts to research more precise immune health grade and immune resilience measures specific to climate change as well as feasible immune interventions. These studies should be performed using both human and non-human primate models.

Authors’ Contributions

All authors contributed to the preparation, writing, and editing of this perspective piece.

Author Disclosure Statement

The authors of this article declare no competing interests.

Funding Information

This publication resulted (in part) from research supported by the Duke University Center for AIDS Research (CFAR), an NIH funded program (5P30 AI064518), and the Duke Center for Human Systems Immunology.