10th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 6-8 November 2008, London, UK

URINE F₂-ISOPROSTANE IS POSITIVELY CORRELATED WITH TRUNK AND TOTAL BODY FAT IN HIV-INFECTED, PROTEASE INHIBITOR-TREATED PERSONS WITH LOW TRADITIONAL CARDIOVASCULAR RISK PROFILE

Antiviral Therapy 2008; 13(Suppl. 4):A38 (abstract no. P-22)

M Boger¹, G Milne², H Erdem¹, V Mitchell¹, D Haas¹ and T Hulgan^1
1Vanderbilt University School of Medicine, Division of Infectious Diseases, Nashville, TN, USA; ²Vanderbilt University School of Medicine, Clinical Pharmacology, Nashville, TN, USA

BACKGROUND: Cardiovascular disease (CVD) is an important non-AIDS-related outcome in HIV-infected persons. Traditional cardiovascular risk factors may underestimate risk in antiretroviral therapy (ART)-treated individuals. Eicosanoids are arachidonic acid metabolites produced from membrane phospholipids by cyclo-oxygenasedependent and -independent pathways. Because these products are mediators and markers of oxidant stress, inflammation and endothelial function, they are attractive as potential cardiovascular biomarkers, but studies are limited. One eicosanoid, urinary F₂-isoprostane-metabolite (IsoP-M), correlated with the number of traditional CVD risk factors and angiographic coronary disease in the general population. We previously showed that IsoP-M was lower in HIV-infected patients on protease inhibitor (PI)-containing ART and positively correlated with high sensitivity C-reactive protein (hsCRP). Thromboxane-metabolite (TxB₂) and prostacyclin-metabolite (PGI-M) were positively correlated with hsCRP and lipids, with sex-specific differences. We compared urinary eicosanoid metabolites and body fat by dual energy X-ray absorptiometry (DEXA) in these HIV-infected, ART-treated subjects.

METHODS: Data are from a cross-sectional analysis of a prospective clinic-based cohort of HIV-infected adults with stable ART (including two or more nucleoside reverse transcriptase inhibitors [NRTIs]), HIV-1 RNA <10,000 copies/ ml, no known CVD or diabetes and no current aspirin or tobacco use. Urine IsoP-M, TxB₂, PGI-M and prostaglandin-E-metabolite (PGE-M) were measured by mass spectrometry/gas chromatography. Anthropometric data included body mass index (BMI), waist-to-hip ratio, and DEXA-determined regional body fat content. Univariate analyses included Spearman correlation and Wilcoxon rank-sum test.

RESULTS: Twenty-six subjects (19 men and 7 women) met inclusion criteria with DEXA and eicosanoid data available. Median age was 46 years, 15 (57%) were of nonwhite race, and 11 (42%) were on PI-containing ART. Median CD4 count and HIV-1 RNA were 592 cells/mm³ and <50 copies/ml, respectively. Median serum lipids were non-high-density lipoprotein (HDL) cholesterol 131 mg/dl, HDL cholesterol 47 mg/dl and triglycerides 170 mg/dl. Median (interquartile range [IQR]) hsCRP was 3.6 (1.1–7.8) mg/dl, indicating high CVD risk, and median (IQR) Framingham risk score was 3 (-2–5) indicating low CVD risk. Median (IQR) BMI and waist-to-hip ratio were 25.5 (23.6–28.1) and 0.89 (0.86–0.93), respectively. IsoP-M correlated positively with absolute (Spearman’s rho 0.41, P=0.04) and percent (0.47, P=0.02) trunk fat, and percent body fat (0.38, P=0.05) by DEXA. These correlations were driven by persons receiving PIs: Spearman’s rho 0.67 (P=0.02) for absolute trunk fat, 0.68 (P=0.02) for percent trunk fat, 0.61 (P=0.05) for absolute body fat and 0.58 (P=0.06) for percent total body fat. Other eicosanoids were not statistically associated with anthropometric measures (including limb fat) in this small sample.

CONCLUSIONS: In this pilot study of non-smoking, nondiabetic ART-treated patients, urine IsoP-M, a marker of systemic oxidant stress associated with CVD risk, correlated with DEXA-derived measures of trunk and total body fat, and these correlations were strongest in persons receiving PI-based ART. Future studies should assess eicosanoids and other measures of lipodystrophy, other metabolic complications and CVD outcomes.

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2008-11-06
P-22

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