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1618
Elevated IP10 Associates with CD8 Cell Activation and Low CD4 in Perinatally Acquired HIV Infection

Session: Poster Abstract Session: HIV: Pediatric
Saturday, October 11, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
Posters
  • poster2014IDSA20140912final.pdf (618.8 kB)
  • Background: High levels of interferon gamma-induced protein (IP10) associate with rapid disease progression, chronic immune activation and HIV-1 replication in adults; however, the association of this cytokine with HIV disease in perinatally HIV infected children and adolescents, is not established.

    Methods: We measure plasma IP10 levels by Luminex and CD8+ T cell activation (HLA-DR+ and CD38+) by flow cytometry.  HIV+ patients are parsed into viremic (n=28) and aviremic (n=11) (HIV RNA < 400 or ≥ 400 copies/ml). Wilcoxon rank-sum is used to compare groups and Spearman’s coefficient is used for correlation analysis.

    Results: 39 HIV+ on cARV [median CD4 % 30.2 IQR (23.2-39.4) and HIV RNA1.8 log10(1.6-3.0) copies/ml] and 14 HIV- are studied. HIV+ have significant higher concentrations of IP10 compared with HIV- (P<0.0001); especially viremic individuals Table 1.  We observe significantly higher % of T cell activation markers in viremic compared with aviremic Table1.  Higher levels of IP10 correlate with higher CD38 % and HLA-DR and lower CD4 %, Table 2. Lastly, early cARV therapy correlates with lower levels of IP10, CD8 %, CD8+ HLA-DR %, and higher CD4 %, Table 2.

    Conclusion: Perinatally HIV infected children and adolescents have a pattern of IP10 elevation comparable to HIV infected adults. Notably, IP10, a product of monocytes and dendritic cells, is significantly elevated-especially in viremic children- and associates with T cell activation and low CD4 %. The results support the view that IP10 is secreted in part as a direct effect of viral replication. Furthermore, our data suggest that early initiation of cARV might help to prevent immune system activation and disease progression in this population.

    Table 1 Immunologic parameters

    Outcome

    HIV-

    Aviremic

    Viremic

    p

    IP10 *

    182.1(118.2-227.6)

    485.9 (289.7-976.1)

    1086.9 (425.8-2408.6)

    <0.001

    CD4+ %

     

    30.9 (23.2-39.2)

    28.0 (19.0-39.0)

    -

    CD8+ %

     

    35.2 (30-47)

    47.2 (32.4-54.1)

    -

    CD8+CD38+ %

     

    12.0 (8.0-14)

    20.5 (16.0-34.0)

    0.001

    CD8+HLA-DR+ %

     

    10.0 (4.0-21)

    23.0 (14.0-33.0)

    0.01

    Table 2 Correlation analysis

     

    IP10

    Early cARV therapy

    Outcome

    r

    p

    r

    p

    CD4 %

    -0.57

    <0.001

    -0.50

    0.001

    CD8 %

    0.43

    0.01

    0.47

    0.002

      CD8+CD38+  %

    0.37

    0.04

    0.13

    0.43

      CD8+ HLA+DR+ %

    0.53

    0.002

    0.32

    0.04

    IP10

     

     

    0.37

    0.03

    *pg/ml; ‡ median (IQR), † Viremic vs HIV-.

    German Contreras, MD MSc1,2, Elizabeth Donnachie, PhD3, James R. Murphy, PhD4 and Gloria P. Heresi, MD4, (1)Pediatric Infectious Disease, UTHealth, Houston, TX, (2)Molecular Genetics Unit, Bogotá, Colombia, (3)Pediatrics, Gulf States Hemophilia and Thrombophilia Center, Houston, TX, (4)Pediatric Infectious Disease, UT Health, Houston, TX

    Disclosures:

    G. Contreras, None

    E. Donnachie, None

    J. R. Murphy, None

    G. P. Heresi, None

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