859. Correlates of natural killer T cells (NKT) and their association with progression to AIDS in HIV-infected women
Session: Poster Abstract Session: HIV: Subpopulations
Friday, October 4, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • 859_IDWPOSTER_update.pdf (2.3 MB)
  • Background: Natural killer T cells (NKT) have been shown to be targeted by HIV-1 and selectively depleted in HIV-infected individuals.  This study examines correlates of NKT cell numbers and their association with progression to AIDS in HIV-infected women in the Women’s Interagency HIV Study (WIHS) without AIDS at baseline.

    Methods: Women are seen every six months to collect a wide array of clinical data and biological specimens for laboratory testing.  Our analysis includes women with at least two NKT (CD3+/CD16+/56+) data evaluations collected from 1994-1997 (N=1,356).  Generalized estimating equation (GEE) models for repeated measures were used to evaluate associations of NKT cell numbers with age, ethnicity, Hepatitis C (HCV) antibody status, smoking, injection drug use (IDU), antiretroviral (ARV) therapy, CD4+ count, CD8+ count and HIV RNA copies/ml over a follow-up of approximately 3.5 years (6,649 visits).  Cox regression was used to estimate the risk (hazard ratio [HR]) of AIDS by NKT levels.  GEE models were also used to evaluate associations between NKT and immune activation markers.  

    Results: After mutual adjustment, significant correlates of lower NKT were higher HIV RNA (p<.01), lower CD4 count (p<.01) and no antiretroviral therapy (p<.01).  Women in the lowest NKT quartile were more likely to progress to AIDS compared to women in the highest quartile after adjusting for age, ethnicity, IDU, ARV therapy, HCV status, and CD4 (HR=1.46, 95% CI 1.00-2.14, p for trend=.02) and HIV RNA (HR=1.60, 95% CI 1.09-2.34, p for trend=.01). When both HIV RNA and CD4 count were in the same model the affect is attenuated (HR=1.39, 95% CI 0.94-2.07, p for trend=.06).  Mean CD4+CD38+DR+ and CD8+CD38+DR+ activation levels were higher for those in the lowest NKT quartile compared to those in the highest quartile (p<.05 for both CD4 and CD8 T-cell activation). 

    Conclusion:

    Increased risk of progression to AIDS was observed for HIV+ women with lower numbers of NKT cells.  Women with lower NKT cells were also more likely to have higher levels of T-cell activation.  Preservation of NKT cell number may play an important role in improved long-term outcomes.

    Toni Frederick, PhD, Research Pediatrics, University of Southern California, Los Angeles, CA, Melissa Frasco, PhD, Preventative Medicine, Keck School of Medicine at USC, Los Angeles, CA, Roksanna Karim, PhD, MBBS, Research Pediatrics, Keck School of Medicine of USC, Los Angeles, CA, Wendy Mack, PhD, Preventive Medicine, Keck School of Medicine at USC, Los Angeles, CA, Jerome Kerzerho, PhD, Molecular Microbiology and Immunology, Keck School of Medicine at USC, Los Angeles, CA, Howard D. Strickler, MD, Albert Einstein College of Medicine, Bronx, NY, Michael Augenbraun, MD, FACP, SUNY Downstate Medical Center, Brooklyn, NY, Mary Young, M.D, Department of Medicine, Georgetown University Medical Center, Washington, DC, Phyllis Tien, MD, San Fransicsco VAMC, San Francisco, CA, Alan Landay, PhD, Rush University Medical Center, Chicago, IL and Andrea Kovacs, MD, Pediatrics, Keck School of Medicine at USC, Los Angeles, CA

    Disclosures:

    T. Frederick, None

    M. Frasco, None

    R. Karim, None

    W. Mack, None

    J. Kerzerho, None

    H. D. Strickler, None

    M. Augenbraun, None

    M. Young, None

    P. Tien, None

    A. Landay, None

    A. Kovacs, None

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