411. Metabolic Abnormalities and Mitochondrial Function in Children with Perinatally-Acquired HIV Infection in the Pediatric HIV/AIDS Cohort Study (PHACS)
Session: Poster Abstract Session: Pediatric HIV
Thursday, October 3, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • Sharma 411_IDWPOSTER.pdf (544.0 kB)
  • Background : Chronic HIV or antiretrovirals (ARV) can cause mitochondrial (mt) dysfunction, a potential mechanism for insulin resistance (IR) which is common in perinatally HIV-infected children (HIV+). Mt dysfunction is also seen in non-HIV+ individuals with exogenous obesity. In a cross-sectional study, we compared mt function (mtfxn) in HIV+ and HIV-exposed, uninfected (HEU) children, and evaluated the association between mtfxn, BMI z-scores (BMIz), and IR.

     

    Methods : HIV+ and HEU were enrolled from the Adolescent Master Protocol of PHACS. Demographics, BMIz, venous lactate, and mtfxn (oxidative phosphorylation [OXPHOS] as measured by NADH dehydrogenase Complex I [CI] enzyme activity, OD/min/g e3) in peripheral blood mononuclear cells were evaluated. ARV use and fasting plasma glucose and insulin were recorded in HIV+. HOMA-IR score was calculated to define IR. Unadjusted differences in mtfxn by HIV status and IR (HIV+ only) were evaluated using Wilcoxon rank sum test. Linear regression models were fit to assess differences in mtfxn by HIV status adjusted for age, race, sex, and BMIz. An interaction term for HIV status by BMIz was tested. Spearman correlations between BMIz and CI activity by HIV status were determined.

     

    Results : 218 HIV+ and 117 HEU were enrolled with no differences by sex, race, or CI activity. Compared to HEU, HIV+ were older (median 15.7 vs. 12.7 yr, p<0.001), had lower BMIz (median 0.39 vs. 0.80, p=0.003), and had lower lactate (median 1.0 vs. 1.8 mM, p<0.001). In adjusted analyses, the relationship between BMIz and CI activity varied significantly by HIV status (p<0.0001). Thus, separate adjusted models were fit for HIV+ and HEU. For each 1 SD increase in BMIz there was 2.79 (SE 1.3, p=0.03) lower CI activity in HIV+ and 4.8 (SE 1.7, p=0.005) higher CI activity in HEU (Figure). HIV+ with IR had higher lactate (median 1.3 vs. 0.95 mM, p<0.001) and lower CI activity (15.8 vs. 21.3, p=0.01) than HIV+ without IR. ARV use did not differ by IR status.

     

    Conclusion : Venous lactate is higher and CI activity is lower in HIV+ with IR than without IR, indicating mt dysfunction in those with IR. The expected positive association between BMI and CI activity, as seen in HEU, is reversed in HIV+ suggesting an abnormally blunted OXPHOS response to a rise in BMIz among HIV+.

    Tanvi Sharma, MD1, Jiajia Wang, MS2, Jody Takemoto, PhD3, Denise Jacobson, PhD, MPH2, Mariana Gershenson, PhD3, Mitchell Geffner, MD4, Laurie Butler, MT, MBA5, Patricia Graham, MS6, Russell Van Dyke, MD7 and Tracie Miller, MD6, (1)Pediatric Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, MA, (2)Harvard School of Public Health, Boston, MA, (3)University of Hawaii School of Medicine, Honolulu, HI, (4)The Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine of USC, Los Angeles, CA, (5)Frontier Science & Technology Research Foundation, Amherst, MA, (6)University of Miami Miller School of Medicine, Miami, FL, (7)Tulane University Health Sciences Center, New Orleans, LA

    Disclosures:

    T. Sharma, None

    J. Wang, None

    J. Takemoto, None

    D. Jacobson, None

    M. Gershenson, None

    M. Geffner, None

    L. Butler, None

    P. Graham, None

    R. Van Dyke, None

    T. Miller, None

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