icon-    folder.gif   Conference Reports for NATAP  
  Conference on Retroviruses
and Opportunistic Infections
Will be Virtual
Boston USA
March 6-10, 2021
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  CROI 2021 March 6-10 Reported by Jules Levin
Corrilynn O . Hileman1, Trong-Tuong Nguyen1, Jared C. Durieux2, Daniela Schlatzer3, Xiaolin Li3, Grace A. McComsey2 1MetroHealth Medical Center, Cleveland, OH, USA, 2University Hospitals Cleveland Medical Center, Cleveland, OH, USA, 3Case Western Reserve University, Cleveland, OH, USA
Background: Tryptophan (TRYP) metabolism via the kynurenine (KYN) pathway has been implicated in the pathogenesis of cardiovascular disease. Downstream metabolites kynurenic acid (KA) and quinolinic acid (QA) are paths for TRYP degradation that may affect risk differently. Inflammatory pathways mediating these effects have not been studied in HIV.
Methods: TRYP, KYN, KA and QA were quantified by LC/MS/MS from adults with and without HIV enrolled in a longitudinal study of carotid intima media thickness (IMT) progression. hsCRP, IL6, sTNF-RI and -RII, ICAM-1 and VCAM-1, D-Dimer and fibrinogen were quantified by ELISA. Data through week 96 was included. Linear mixed effects modeling with stratified propensity score matched on age, sex, race, smoking and BMI was utilized. Direct and indirect effects of inflammation markers were tested where associations between TRYP metabolites and IMT were significant.
Results: 123 adults were included (47 HIV+ initiating ART; 31 HIV+ remaining ART-naïve; 45 HIV-). Median age was 40 yrs; 73% male; with BMI 27 kg/m2. There were more blacks and current/former smokers in HIV+ (59 vs 27% and 68 vs 31%; both p<0.01). HIV duration (4 yrs) and HIV-1 RNA (2461 copies/ml) were similar among HIV+, but nadir CD4+ was lower in HIV+ initiating ART (340 vs 505 cells/mm3; p<0.01). There were differences in TRYP metabolites between groups at baseline and over time (Figure). Notably, in HIV+ initiating ART group, both steepness and at times direction of change in the first year after ART initiation were different from HIV+ remaining ART-naïve and HIV-. Baseline QA and QA:KA ratio (trend) were associated with higher time-updated common carotid artery (CCA) IMT (ρ=0.05; p=0.04 and ρ=0.04; p=0.06), but effects attenuated with adjustment (ρ=0.04; p=0.07 and ρ=0.03; p=0.11). Baseline QA, KYN and KYN:TRYP ratio (trend) were associated with higher time-updated carotid bulb IMT even with adjustment (QA: ρ=0.07; p=0.04, KYN: ρ=0.14; p<0.05 and KYN:TRYP ratio: ρ=0.1; p=0.09). sTNF-RII, D-Dimer and fibrinogen mediated the effect between QA and CCA IMT, while IL6, sTNF-RI and fibrinogen mediated the effect between QA and bulb IMT; no mediators between KYN and bulb IMT were identified.
Conclusion: QA, but not KA, was associated with both CCA and bulb IMT, and inflammatory and coagulation markers appear to mediate these effects. Also, TRYP metabolites were associated more closely with bulb IMT, the site with the highest inflammatory milieu. ART initiation appears to impact TRYP metabolite levels.