Microbiota, Gender-Affirming Hormone Therapy, and Inflammatory Biomarkers in Transgender Women with HIV: Potential Implications for Cardiovascular Disease

Purpose: The intersecting disparities of human immunodeficiency virus (HIV) and cardiovascular disease (CVD) among transgender women have raised questions about the role of the gut microbiota and gender-affirming hormone therapy (GAHT) in the pathogenesis of CVD in the context of HIV. The purpose of this study was to provide an early exploration of the associations between these possible mechanisms driving inflammatory CVD risk markers among transgender women with HIV. Methods: We conducted a preliminary study with 21 transgender women with HIV exploring the relationship between GAHT use (self-report), gut/rectal microbiota composition (rectal swabs), and inflammatory markers linked to CVD (plasma). Microbiota measures included alpha (richness, evenness, and Shannon diversity) and beta (Bray-Curtis, un/weighted UniFrac) diversity metrics. Inflammatory biomarkers included intestinal fatty-acid binding protein, monocyte chemoattractant protein-1, soluble CD163, intercellular adhesion molecule 1, tumor necrosis factor alpha (TNFa), soluble TNF receptor I (sTNF-I), sTNF-II, interleukin (IL)-6, IL-8, IL-1b, IL-1a, soluble CD14, d-dimer (domain dimer), vascular cell adhesion molecule 1, and high-sensitivity C-reactive protein. Wilcoxon rank sum test, log-level regression, Spearman’s rho, permutational multivariate analysis of variance, and differential abundance testing assessed relationships between constructs. Results: Key inflammatory markers linked to CVD were associated with GAHT use—an increased sTNF-I and sTNF-II levels and decreased IL-1a levels. Microbiota composition was not related to GAHT use but was variably associated with inflammatory biomarkers related to CVD risk. Conclusions: Although preliminary, these findings suggest a potential association between inflammation linked to CVD risk and microbiota composition and GAHT. The results contribute to the characterization of interconnecting factors that may inform understanding and interventions to enhance overall health and well-being in transgender women with HIV. Further research is essential to elucidate the mechanisms underlying these associations, ultimately striving for health equity.