Introduction: Dyslipidemia in HIV - May arise from viral infection, antiretroviral treatment and changes in body composition 1 - Is a key metabolic abnormality believed to underlie increased CVD risk Oxidative stress and mitochondrial function: - Is linked to atherosclerosis 2 and HIV treatment 3 Nisha I Parikh MD MPH 1,2, Mariana Gerschenson PhD 3, Mary S. Lopez B.S. 3, Todd Seto MD MPH 1, 2, Dominic Chow MD 2, Cecilia Shikuma MD 2 1. Queens Medical Center, Honolulu HI 2. Hawaii Center for AIDS Research, Department of Medicine, University of Hawaii, HI 3. Department of Cell and Molecular Biology, University of Hawaii, HI. This research was funded by DHHS/NIH grant # HL The investigators have declared no conflict of interests. Mitochondrial Oxidative Stress and Function compared to Lipoprotein Level, Particle Number and Size in an HIV Positive Cohort No significant associations between mitochondrial oxidative stress and function with standard clinical lipid profile (decreased Complex I activity related to LDL-C and total-C with borderline significance). 8-oxo-DG related to small HDL particles and to VLDL size Decreased Complex I activity related to VLDL+ chylomicrons and LDL particle number Decreased Complex I activity related to small LDL and small VLDL Complex IV is not related to any lipid parameters Table 1: Characteristics of Study Participants In an HIV infected cohort on stable antiretroviral therapy, to determine the relationship between mitochondrial oxidative stress and function and 1. Standard clinical lipid profile 2. Lipoprotein subclass particle concentration 3. Lipoprotein subclass size OBJECTIVES METHODS RESULTS IMPLICATIONS CONCLUSIONSINTRODUCTION Table 2: Mitochondrial Oxidative Stress and Function and Traditional Directly Measured Lipid Panel (Adjusted for Age and Gender) Table 4: Mitochondrial Oxidative Stress and Function and Lipid Particle Size By NMR Spectroscopy (Adjusted for Age and Gender) Table 3: Mitochondrial Oxidative Stress and Function and Lipid Subclass Concentration and Particle Number by NMR Spectroscopy (Adjusted for Age and Gender) Study Sample: HIV infected individuals, age > 40 years and on stable highly active antiretroviral therapy for > 6 months. Location: Oahu, Hawaii. N=87 Lipid measurements (fasting): - Standard lipid profile: directly measured - Liposcience Assay 4 : nuclear magnetic resonance (NMR) spectroscopic analysis Mitochondrial Oxidative Stress and Function Measurements (using peripheral blood mononuclear cells) - Stress: Mitochondrial-specific 8-oxo-guanine (8-oxo-dG) was measured using the gene specific repair assay. 5 Units are break frequencies (BFs) - Function: Mitochondrial OXPHOS enzymes, NADH dehydrogenase (Complex I) and cytochrome c oxidase (Complex IV) enzyme activities were measured by thin layer chromatography and immunoassay. 6 Units are optical density(O.D.)/ ug protein Statistical Methods: -Descriptive statistics (n, mean, standard deviations percentages) for baseline characteristics. -Age and gender adjusted linear regression analysis to relate mitochondrial and lipid parameters (standard lipid panel, lipid subclass and lipid subclass size) - A p-value of <0.05 was considered significant. Mitochondrial oxidative stress and function are related to LDL, HDL and VLDL particle size and number but not to traditional lipid measures Traditional lipid profiles may not fully capture the atherogenic lipid risk among persons infected with HIV on stable HAART REFERENCES 1.Hadigan C et al. Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy. Clin Infect Dis 2001;32: Vassalle MG and Zucchelli GC. Oxidative stress and its association with coronary artery disease and different atherogenic risk factors. J Intern Med 2004;256: Masia M et al. Influence of antiretroviral therapy on oxidative stress and cardiovascular risk: a prospective cross-sectional study in HIV-infected patients. Clin Ther 2007;29: Jeyarajah EJ et al. Lipoprotein Particle Analysis by Nuclear Magnetic Resonance Spectroscopy. Clin Lab Med 26 (2006) 847– Gerschenson M, et al., Mitochondrial function, morphology and metabolic parameters improve after switching from stavudine to a tenofovir- containing regimen.J AntimicrobChemother Jun;63(6): Brogly SB, et al. Short communication: transplacental nucleoside analogue exposure and mitochondrial parameters in HIV-uninfected children. AIDS Res Hum Retroviruses Jul;27(7): BFs=Break Frequencies O.D.=optical density