Methods: Demographic and clinical data were obtained prospectively from HIV+ adults in three clinical cohorts who were on stable ART with plasma HIV-1 RNA <50 copies/mL. Urine F2-isoprostane (F2-IsoP), prostaglandin E2 (PGE-M), prostacyclin (PGI-M), and thromboxane B2 (TxB2) metabolites were quantified using gas or liquid chromatography-mass spectroscopy, and normalized to mg creatinine (cr). Wilcoxon signed-rank test and Spearman’s correlation assessed cross-sectional associations with eicosanoid metabolites.
Results: Of 141 participants, 51% were female, 29% white, median age 47 years, CD4 count 552 cells/mm3, and BMI 27.5 kg/m2. Females had higher median F2-IsoP (2.2 vs. 1.5 ng/mg cr, p=0.002) and TxB2 levels (0.4 vs. 0.2 ng/mg cr, p=0.001) and lower PGE-M (6.2 vs. 9.2 ng/mg cr, p=0.009) compared to males. F2-IsoP (2.4 vs. 1.6 ng/mg cr, p<0.001), PGI-M (0.2 vs. 0.1 ng/mg cr, p=0.002) and TxB2 (0.4 vs. 0.2 ng/mg cr, p<0.001) were higher in smokers (N=59) than non-smokers. Hepatitis C virus (HCV; N=18) co-infected persons had higher F2-IsoP (2.5 vs. 1.9 ng/mg cr, p=0.005) and TxB2 (0.4 vs. 0.3 ng/mg cr, p=0.006) than HIV mono-infected. PGI-M levels inversely correlated with BMI (r=-0.22, p=0.01), waist circumference (r=-0.23, p=0.008), and waist-hip ratio (r=-0.18, p=0.04). In males, BMI (r=-0.28, p=0.02) and waist circumference (r=-0.26, p=0.04) inversely correlated with F2-IsoP. TxB2 correlated with sCD14 (r=0.25, p=0.004) and IL-6 (r=0.27, p=0.002).
Conclusion: In the largest study to date of urine eicosanoids in HIV+ adults on suppressive ART, notable differences in eicosanoid metabolites were observed by sex, smoking, and HCV co-infection. Correlations with the mortality-associated biomarkers sCD14 and IL-6 were also observed. These results support urine eicosanoids as potentially relevant markers for assessment in prospective studies of HIV+ persons.
GlaxoSmithKline: Consultant and Investigator , Consulting fee and Research support
C. H. Tseng, None
T. Hulgan, None