Sex Differences in Urinary Biomarkers of Vascular and Endothelial Function in HIV-Infected Persons Receiving Antiretroviral Therapy

BACKGROUND: Cardiovascular disease (CVD) risk can be underestimated in HIV-infected patients receiving antiretroviral therapy (ART). Novel CVD risk markers in this population are needed. We hypothesized that eicosanoid metabolite production is increased with metabolic complications of ART. Our objective was to determine relationships between urine eicosanoids and traditional CVD risk factors in a cohort of HIV-infected persons receiving ART. METHODS: Cross-sectional analysis of 107 individuals from a prospective cohort study with urine eicosanoids (isoprostane [15-F(2t)-IsoP], prostaglandin-E metabolite [PGE-M], thromboxane metabolite [11dTxB(2)], prostacyclin metabolite [PGI-M]) determined by gas or liquid chromatography-mass spectrometry. RESULTS: 15-F(2t)-IsoP was higher (P=0.003), 11dTxB(2) tended to be higher (P=0.07) and PGE-M was lower (P=0.003) in females than in males. The overall median Framingham score was 4 (IQR 1-7). In multivariable analyses adjusting for age, CD4(+) T-cells, smoking status, non-steroidal anti-inflammatory drug use, aspirin use and body mass index (BMI), associations included: higher 15-F(2t)-IsoP with female sex (P=0.004) and current smoking (P=0.04), lower PGE-M with female sex (P=0.005) and higher BMI (P=0.03), higher 11dTxB(2) with increasing age (P=0.02) and current smoking (P=0.04), lower 11dTxB(2) with higher BMI (P=0.02), and higher PGI-M with current smoking (P=0.04). CONCLUSIONS: In this pilot study of predominantly virologically suppressed HIV-infected individuals on ART, there were sex-specific differences in urinary eicosanoids, with females having more risk-associated parameters despite a low Framingham score. Eicosanoids might be useful CVD biomarkers in ART-treated, HIV-infected patients. Future studies should examine eicosanoids while assessing effects of specific ART regimens and targeted interventions on CVD outcomes.