Food Insecurity and Undernutrition Are Associated With Distinct Immunologic Profiles in People With Tuberculosis and Advanced HIV Starting Antiretroviral Therapy

Abstract

Background: Food insecurity and undernutrition are related but distinct concepts contributing to poor HIV and tuberculosis outcomes. Pathways linking them with immunologic profile, which may relate to clinical outcomes, remain understudied.

Methods: We analyzed data from a cohort study of 165 antiretroviral therapy (ART)-naïve adults with advanced HIV and newly diagnosed tuberculosis in Botswana from 2009 to 2013. Twenty-nine plasma biomarkers were measured pre-ART and 4 weeks post-ART initiation. We used principal components analysis (PCA) and multivariable linear regression models to assess relationships between immunological profiles and food insecurity (based on the Household Food Insecurity Access Scale), undernutrition (body mass index <18.5 kg/m 2 ), and clinical outcomes.

Results: PCA identified 5 principal components with eigenvalues >1. After adjustment, food insecurity was associated with PC3 pre-ART (0.19 per increased category of severity, 95% CI: 0.02 to 0.36) and post-ART (0.24, 95% CI: 0.07 to 0.41). PC3 was driven by higher levels of IFN-α, IFN-γ, interleukin (IL)-12p40, vascular endothelial growth factor, IL-1α, and IL-8 and decreased concentrations of IL-3. Undernutrition was associated with PC5 post-ART (0.49, 95% CI: 0.16 to 0.82). PC5 was driven by higher levels of IL-8, MIP-1α, IL-6, and IL-10 and decreased concentrations in IP-10 and IFN-α. Post-ART PC3 (4.3 percentage point increased risk per increased score of 1, 95% CI: 0.3 to 8.9) and post-ART PC5 (4.8, 95% CI: 0.6 to 8.9) were associated with death in adjusted models.

Discussion: We identified 2 distinct immunologic profiles associated with food insecurity, undernutrition, and clinical outcomes in patients with advanced HIV and tuberculosis. Different pathophysiologic processes may link food insecurity and undernutrition with poor outcomes in this vulnerable patient population. Future studies should assess the impact of improving food access and intake on immune function and clinical outcomes.

Figure 1.

Conceptual model showing pathways between food insecurity, undernutrition, and HIV/TB outcomes, and highlighting the central research question of this analysis related to immunologic profiles associated with food insecurity and undernutrition. Dotted lines represent potential consequences of HIV/TB that may feed into vicious cycles with food insecurity or undernutrition.

Figure 2.. Principal Component Analysis Scores and Weightings.

(A) Scree plot showing eigenvalues of the principal components, with a horizontal line at an eingenvalue of 1 (B) Cumulative proportion of variance explained by the principal components (C) Variance of each of the first five principal components amongst all participants (D) Heat map showing the loadings of each baseline biomarker for the first five principal components.

Figure 3.. Post-ART associations between food insecurity and undernutrition with individual log-transformed biomarkers substantially contributing to principal component 3 (for food insecurity) and principal component 5 (for undernutrition).

Reference groups are the food secure participants, and participants without undernutrition.All estimates use adjusted for age, sex, extrapulmonary TB, non-TB opportunistic infection, number of days between initiating anti-TB therapy and ART, baseline CD4 count, and baseline HIV log viral load.

Figure 3.. Post-ART associations between food insecurity and undernutrition with individual log-transformed biomarkers substantially contributing to principal component 3 (for food insecurity) and principal component 5 (for undernutrition).

Reference groups are the food secure participants, and participants without undernutrition.All estimates use adjusted for age, sex, extrapulmonary TB, non-TB opportunistic infection, number of days between initiating anti-TB therapy and ART, baseline CD4 count, and baseline HIV log viral load.