Body talk: Correlates of gut-immune dysregulation phenotypes in people living with HIV who use methamphetamine
Article
Vincent, W, Flentje, A, Dominguez, BS et al. (2026). Body talk: Correlates of gut-immune dysregulation phenotypes in people living with HIV who use methamphetamine
. 51 10.1016/j.bbih.2025.101156
Vincent, W, Flentje, A, Dominguez, BS et al. (2026). Body talk: Correlates of gut-immune dysregulation phenotypes in people living with HIV who use methamphetamine
. 51 10.1016/j.bbih.2025.101156
Background: Microbial translocation, immune activation, inflammation, and dysregulated metabolism of neurotransmitter precursors are interacting pathophysiologic processes linked to neuropsychiatric comorbidities and faster HIV disease progression. We examined correlates of distinct phenotypes of gut-immune dysregulation in people living with HIV (PWH) who use methamphetamine. Methods: Participants were 122 PWH who had biochemically confirmed recent methamphetamine use, including non-injection use. Peripheral plasma markers reflected: intestinal permeability, microbial translocation, immune activation, inflammation, and dysregulated metabolism of neurotransmitter precursors. Using latent profile analysis (i.e., clustering) of these markers, we identified gut-immune phenotypes and their clinical, demographic, and stigma-related correlates. Results: Three immune profiles emerged: (1) low gut-immune dysregulation with lower microbial translocation, macrophage activation, inflammation, and tryptophan catabolism; (2) moderate gut-immune dysregulation with all markers within average range; and (3) high gut-immune dysregulation with higher microbial translocation, immune activation, inflammation, and tryptophan catabolism. In adjusted analyses, higher viral load (one log10 copy/ml; AOR = 1.97, 95 % CI = 1.02–3.82), injection of methamphetamine (AOR = 3.60, 95 % CI = 1.23–10.50), and internalized stigma (AOR = 1.78, 95 % CI = 1.01–3.15) were associated with having a moderate gut-immune dysregulation profile. Additionally, higher viral load (AOR = 2.98, 95 % CI = 1.53–5.24) and injecting methamphetamine (AOR = 5.45, 95 % CI = 1.34–17.78) were associated with having a high gut-immune dysregulation profile. Conclusions: Distinct patterns of microbial translocation, immune activation, inflammation, and metabolism of amino acid precursors distinguished gut-immune phenotypes of PWH reporting injection methamphetamine use and greater internalized stigma. Interventions tailored to PWH who inject methamphetamine or struggle with internalized stigma could optimize HIV-related health outcomes.
