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

Objective: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. Design:This is a cross-sectional, observational study exploring the associations between peripheral inflammation and metabolism in treatment-naive South African people with HIV. Methods: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. Results: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. Conclusions: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."