The relationship between immune markers and tryptophan-kynurenine metabolites in South African people with HIV

HIV-1 remains a global challenge, especially in high-prevalence areas like South Africa. This study explores the relationship between inflammation and metabolism in people with HIV, focusing on immune markers and the tryptophan-kynurenine (Trp-Kyn) pathway. We examined immune markers (hsCRP, suPAR, IL-6, NGAL, and sCD163) and Trp-Kyn metabolites (QUIN, Trp, Kyn, Trp/Kyn ratio, and kynurenic acid) in n = 69 treatment-naive South African people with HIV. Using targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics and various assays, we observed significant associations between immune markers and Trp-Kyn metabolites. IL-6 was negatively associated with Trp (P < 0.001) and positively with the Kyn/Trp ratio (P = 0.005). hsCRP was positively associated with QUIN (P = 0.036). suPAR showed significant negative associations with Trp (P = 0.036), positive associations with the Kyn/Trp ratio (P < 0.001), and QUIN (P = 0.007). sCD163 negatively associated with Trp (P < 0.001) and positively with the Kyn/Trp ratio (P < 0.001). When participants were stratified by inflammation levels (based on CRP), IL-6 (P = 0.002), QUIN (P = 0.009), and Kyn (P = 0.032) were significantly higher in the high inflammation group. Specific associations were observed only in certain groups, such as IL-6 negatively associating with Trp and kynurenic acid in the high inflammation group, and suPAR associating negatively with Trp in the low inflammation group. These exploratory findings provide further insight into how peripheral inflammation and metabolism are interrelated in South African people with HIV, potentially guiding future therapeutic strategies.