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Food Insecurity Affects HIV+ Minorities & Associated with Comorbidities & Mortality
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"Food insecurity is a social determinant of health that disproportionately affects US minorities [9] and PWH [10] and is associated with several chronic conditions and increased mortality rates among US adults....Public health strategies to curve food insecurity are also needed.....Notably, the association between food insecurity and sCD14 suggests increased microbial translocation-a major pathway of immune activation in PWH.....Diet quality may explain some of the relationship between food insecurity, immune activation and inflammation, and chronic disease. Indeed, food insecurity often leads to dependence on low-cost foods, resulting in poor-quality diets that are high in fats, simple sugars, and refined carbohydrates but low in essential nutrients and fiber. Micronutrients play critical roles in immunity and their deficiency can contribute to immune activation and inflammation......These results, as well as those reported herein, point to biological pathways between food insecurity and chronic disease. For example, among Latinos with type 2 diabetes, increased stress (cortisol) and inflammation (CRP) partially mediated the relationship between food insecurity and insulin resistance, the precursor for type 2 diabetes"
In conclusion, food insecurity was associated with markers of immune activation in the MASH cohort, suggesting a biological link between food insecurity and chronic disease among PWH. Our findings suggest that improving financial security, access to high-quality foods, and nutrition knowledge could lead to significant health benefits in this highly vulnerable population. In addition, screening for food insecurity may be a cost-efficient method of risk assessment and reducing the high burden of disease among PWH. Mechanisms for the effect of food insecurity on immune activation remain to be elucidated. Future research should consider diet quality and gut permeability as potential mediators of food insecurity and immune activation.
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Immune Activation: A Link Between Food Insecurity and Chronic Disease in People Living With Human Immunodeficiency Virus
The Journal of Infectious Diseases 16 May 2021 - Javier A. Tamargo,1, Jacqueline Hernandez-Boyer,1 Colby Teeman,1, Haley R. Martin,1 Yongjun Huang,1 Angelique Johnson,1 Adriana Campa,1, Sabrina S. Martinez,1 Tan Li,2 Susan D. Rouster,3 Heidi L. Meeds,3 Kenneth E. Sherman,3 and Marianna K. Baum1,
1Department of Dietetics and Nutrition, Florida International University, Miami, Florida, USA; 2Department of Biostatistics, Florida International University, Miami, Florida, USA; and 3University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Abstract
Persistent immune activation is a hallmark of human immunodeficiency virus (HIV) infection and thought to play a role on chronic diseases in people with HIV (PWH). Food insecurity is disproportionately prevalent in PWH and is associated with adverse health outcomes. We determined whether food insecurity was associated with increased plasma levels of soluble CD14, CD27, and CD163 in 323 antiretroviral-treated PWH from the Miami Adult Studies on HIV cohort. Nearly half (42.7%) of participants were food insecure, and 85.5% were virally suppressed (<200 copies/mL). Food insecurity was independently associated with higher levels of soluble CD14 and soluble CD27. Very low food security was associated with increased soluble CD163 levels among those with lower CD4+ cell counts. Food insecurity may promote immune activation in PWH, suggesting a biological link between food insecurity and chronic disease among PWH. Improving financial security and access to high-quality diets could reduce the burden of disease in this highly vulnerable population.
In addition to food insecurity and HIV viral load, markers of immune activation were associated with older age, race/ethnicity, higher BMI, hypertriglyceridemia, hypertension, higher hs-CRP, and liver fibrosis. Higher CD4+ cell counts were associated with lower sCD27 levels. Trends were observed with cigarette smoking and cocaine use. Dietary intakes of total energy, macronutrients, saturated fatty acids, and fiber were not associated with any of the outcomes.
Food insecurity is a social determinant of health that disproportionately affects US minorities [9] and PWH [10] and is associated with several chronic conditions and increased mortality rates among US adults [11, 12]. In the current study, we showed a direct association between food insecurity and immune activation among PWH from the MASH cohort, a vulnerable population largely comprising socioeconomically disadvantaged black and Hispanic adults who are engaged in HIV care and virally suppressed. At least some level of food insecurity was reported by nearly half of the participants (43%). Food insecurity was independently associated with increased plasma levels of sCD14 and sCD27, which were also directly correlated with the severity of food insecurity. In addition, very low food security and low CD4+ cell counts, together, predicted higher sCD163 levels. Importantly, immune activation is thought to play a key role in HIV disease progression, as well as in the development and progression of chronic conditions [4, 5]. Our findings, therefore, provide insights into a potential link between food insecurity and adverse health outcomes among low-income PWH who are on suppressive ART.
DISCUSSION
Food insecurity is a social determinant of health that disproportionately affects US minorities [9] and PWH [10] and is associated with several chronic conditions and increased mortality rates among US adults [11, 12]. In the current study, we showed a direct association between food insecurity and immune activation among PWH from the MASH cohort, a vulnerable population largely comprising socioeconomically disadvantaged black and Hispanic adults who are engaged in HIV care and virally suppressed. At least some level of food insecurity was reported by nearly half of the participants (43%). Food insecurity was independently associated with increased plasma levels of sCD14 and sCD27, which were also directly correlated with the severity of food insecurity. In addition, very low food security and low CD4+ cell counts, together, predicted higher sCD163 levels. Importantly, immune activation is thought to play a key role in HIV disease progression, as well as in the development and progression of chronic conditions [4, 5]. Our findings, therefore, provide insights into a potential link between food insecurity and adverse health outcomes among low-income PWH who are on suppressive ART.
Notably, the association between food insecurity and sCD14 suggests increased microbial translocation-a major pathway of immune activation in PWH [30]. sCD14 is shed by CD14-expressing monocytes after stimulation by LPS [20]. Consequently, sCD14 is highly correlated with LPS levels [31] and serves as an indirect, yet nonspecific marker of microbial translocation [20, 32]. The poor-quality diets associated with food insecurity may lead to alterations in the diversity of gut microbiota and loss of mucosal barrier defenses, resulting in increased gut permeability and microbial translocation [33].
High-fat diets, in particular, have been shown to alter gut microbiota and disrupt the intestinal barrier, inducing systemic inflammation [18, 34]. In contrast, fiber plays an important role in maintaining gut integrity, as certain undigested carbohydrates are metabolized by gut microbes producing beneficial short-chain fatty acids. While we did not find significant relationships between diet and immune activation, food-insecure participants had higher intake of fat than food-secure participants. In addition, more than half of participants (53%) consumed >10% of total energy from saturated fats, and fiber intake (mean [SD], 13.2 [10.7] g) was well below the recommendations for adults >50 years of age (22.4 g for women and 28 g for men).
The association between food insecurity and sCD27 may have other implications. CD27 is a transmembrane glycoprotein belonging to the tumor necrosis factor receptor family. Although the immunological function of sCD27 has not been fully elucidated, circulating sCD27 induces immunoglobulin G production and is implicated in AIDS-associated lymphoma [24]. Thus, our findings may reflect an increased risk for cancer in association with food insecurity, which is consistent with previous observations [35].
With regard to sCD163, we found that very low food security was associated with increased levels of sCD163 once we accounted for an interaction effect between the severity of food insecurity and CD4+ cell counts. The results therefore suggest that the severity of food insecurity may modify the relationship between immune activation and immunodeficiency in PWH, possibly related to poor engagement in treatment [13, 36]. These findings further support a role of microbial translocation, because LPS promotes shedding of sCD163 in plasma [37]. Interestingly, very low food security was associated with not having a suppressed viral load, but not with CD4+ cell counts.
The findings in the current report are consistent with previous research. Population-based studies have established an association between food insecurity and CRP, a marker of systemic inflammation [16, 17]. Notably, Gowda et al [16] showed that the relationship between food insecurity and CRP was partially mediated by elevated white blood cell counts, suggesting a potential role of immune activation.
In recent years, food insecurity has been associated with elevated inflammation (interleukin 6 and tumor necrosis factor receptor 1) [18], as well as CD4+ and CD8+ activation (percentage CD38+HLADR+) and other markers of immune dysregulation (percentage CD57+CD28− and CD57−CD28+) in women living with HIV who were mostly virally suppressed [19]. These results, as well as those reported herein, point to biological pathways between food insecurity and chronic disease. For example, among Latinos with type 2 diabetes, increased stress (cortisol) and inflammation (CRP) partially mediated the relationship between food insecurity and insulin resistance, the precursor for type 2 diabetes [38]. In another study, food insecurity was associated with the primary allostatic system (neuroendocrine and inflammatory), which incorporated serum cortisol and CRP as biomarkers of stress and inflammation, respectively [39]. Although our data did not show an association between food insecurity and hs-CRP, hs-CRP was correlated with sCD14 and showed a trend with sCD27.
Diet quality may explain some of the relationship between food insecurity, immune activation and inflammation, and chronic disease. Indeed, food insecurity often leads to dependence on low-cost foods, resulting in poor-quality diets that are high in fats, simple sugars, and refined carbohydrates but low in essential nutrients and fiber [8]. Micronutrients play critical roles in immunity and their deficiency can contribute to immune activation and inflammation. Moreover, Bergmans et al [15] reported on the association between food insecurity and inflammatory potential of the diet, showing a dose-response relationship between the severity of food insecurity and the Dietary Inflammatory Index scores. In our study, we found that levels of sCD14 and sCD27 were directly correlated with the severity of food insecurity. One may surmise that as the severity of food insecurity increases, so does the immunoinflammatory potential of the diet.
However, diet alone does not entirely explain the relationship between food insecurity and health outcomes. Other potential mechanisms include poor disease management [36, 40], chronic stress [38], and competing financial constraints, such as having to make tradeoffs between food and medication [41] while having increased healthcare expenditures [42]. Food insecurity is also associated with high rates of substance use [43, 44], which may also contribute to poor health. Indeed, we observed trends between cigarette smoking and sCD27 levels, as well as between cocaine use and sCD14 levels. Both smoking and cocaine have been associated with immune activation in PWH [45, 46].
To summarize, food insecurity was associated with increased biomarkers of immune activation sCD14, sCD27, and sCD163 in PWH from the MASH cohort. The present study is strengthened by the use of validated assessments among a well-characterized cohort of PWH. While we controlled for intake of energy, macronutrients, saturated fatty acids, and fiber, future studies may consider the impact of diet quality and microbial translocation on the relationship between food insecurity and immune activation. The cross-sectional design does not allow establishment of causality, and it is possible that some of the effects observed may be related to unmeasured factors. However, our findings remained consistent even after controlling for several sociodemographic and comorbid confounders. Our findings are also consistent with findings of prior research. Longitudinal studies may provide a more thorough understanding of the causal and temporal relationships between food insecurity, immune activation, and chronic disease outcomes.
Food insecurity is a key social determinant of health, and a growing body of research continues to shed light on its pervasive effects on vulnerable populations. Standardized screening for food insecurity in low-income clinical settings may prove advantageous in relieving disease burden through early identification and intervention. Indeed, healthcare providers can play a critical role in addressing food insecurity by recognizing its role in health and well-being and taking active steps toward incorporating it into their practice. Some recommend using the "SEARCH" approach (screen, educate, adjust, recognize, connect, and help) [47]. However, many healthcare providers fear that screening for food insecurity may damage the patient's relationship with the provider and reduce patient satisfaction [48]. Others may not recognize food insecurity as a medical problem. However, the most likely barrier to screening appears to be concerns about not knowing how to manage food insecurity [48]. It may be that food insecurity interventions should start at the clinician level by increasing awareness, knowledge of available resources, and self-efficacy in managing patients' food insecurity. Indeed, there is a great need for high-quality research on healthcare-based food insecurity interventions [49]. The findings of the current study have further implications for HIV care providers, because immune activation can contribute to HIV disease progression and affect the outcome of comorbid conditions.
Public health strategies to curve food insecurity are also needed. Participation in the Supplemental Nutrition Assistance Program (SNAP)-the largest food-assistance program in the United States-is often insufficient to relieve monetary constraints. Although most eligible individuals participate in this program, the current criteria for eligibility prevent many from obtaining this benefit. Furthermore, some have recently argued that while food insecurity has been increasingly recognized, the aspect of nutrition within food security has been largely overlooked [50]. For example, food security assessments rarely evaluate nutritional status and diet quality. Rather, these authors call for a shift in focus toward "nutrition security" [50].
In conclusion, food insecurity was associated with markers of immune activation in the MASH cohort, suggesting a biological link between food insecurity and chronic disease among PWH. Our findings suggest that improving financial security, access to high-quality foods, and nutrition knowledge could lead to significant health benefits in this highly vulnerable population. In addition, screening for food insecurity may be a cost-efficient method of risk assessment and reducing the high burden of disease among PWH. Mechanisms for the effect of food insecurity on immune activation remain to be elucidated. Future research should consider diet quality and gut permeability as potential mediators of food insecurity and immune activation.
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