1510. Hepatitis C Virus Diversity and Liver Disease Development in HIV/HCV Co-infected Women
Session: Poster Abstract Session: HIV and Co-infections
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • 42589_IDWPOSTER_update.pdf (2.5 MB)
  • Background: HIV has been shown to accelerate the development of liver fibrosis in HIV+HCV+RNA+ patients, but factors that contribute to this pathogenesis are unknown. HCV infection is a major cause of morbidity and mortality in the post-HAART era.  Treatment of HCV infection with direct-acting antivirals (DAA) may allow for cure of HCV soon. However, little is known about the impact of HCV quasispecies diversity on progression to liver disease and the relationship to treatment outcome in HIV/HCV co-infected individuals.

    Methods: Participants in the Women’s Interagency HIV Study (WIHS), an ongoing prospective cohort of HIV among US women, were studied. We conducted a nested case-control study to investigate the relationship between HCV quasispecies diversity and development of liver disease. Presence of liver disease was defined as aspartate aminotransferase to platelet ratio index (APRI) >1.5 or FIB-4 >3.25 at 2 consecutive study visits or liver disease-related death prior to initiation of HAART.  A heteroduplex mobility assay (HMA) was used to evaluate HCV E1E2/HVR1 genetic diversity in 162 plasma samples from 81 HIV/HCV co-infected women (29 cases with liver disease and 54 controls without liver disease). Complexity and pattern of diversity were evaluated visually by counting heteroduplex bands (HetB): ‘no-diversity’ was defined as having no HCV HetB; ‘diversity’ if there were >1 HCV HetB. Presence (≥ 1) of HetB was used as a predictor for liver disease. Logistic regression models were used to determine the association between liver disease and presence of HetB.

    Results: We detected HetB in 102 samples; for 60 samples no HetB were detected.  The absence of bands (no-diversity) was associated with liver fibrosis (OR=3.9, 95% CI=0.87-17.23), adjusting for age, visit when disease was ascertained, HIV RNA level, CD4 count, injection drug use (IDU) and alcohol use in previous 6 months.  Heavy alcohol use (OR=13.1, 95% CI=2.10-81.37) was also associated with presence of liver disease in the multivariate model.  

    Conclusion: HCV HVR1 genetic homogeneity/diversity in HIV/HCV patients may be useful in predicting progression to liver disease. HMA is a simple, fast, and cost effective method to assess for HCV diversity or homogeneity.

    Jiaao Xu, MBBS1, Eva Operskalski, PhD2, Hui Zhou, MS1, Wendy J. Mack, PhD1, Roksana Karim, PhD, MBBS3, Barbara Weiser, MD4, Harold Burger, PhD, MD4, Mark H. Kuniholm, PhD5, Brian Edlin, MD6, Chenglong Liu, MD, PhD7, Marion G. Peters, MD8, Audrey French, MD9, Elizabeth T. Golub, PhD10, Gerald B. Sharp, DrPH11 and Andrea Kovacs, MD12, (1)University of Southern California, Los Angeles, CA, (2)Pediatrics, University of Southern California, Los Angeles, CA, (3)Research Pediatrics, Keck School of Medicine of USC, Los Angeles, CA, (4)Sacramento VA Medical Center, Mather, CA, (5)Department Of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, (6)SUNY Downstate College of Medicine, Brooklyn, NY, (7)Georgetown University Medical Center, Washington, DC, (8)University of California at San Francisco, San Francisco, CA, (9)John H. Stroger, Jr. Hospital of Cook County, Chicago, IL, (10)Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, (11)National Institutes of Health, Bethesda, MD, (12)Pediatrics, Keck School of Medicine at USC, Los Angeles, CA

    Disclosures:

    J. Xu, None

    E. Operskalski, None

    H. Zhou, None

    W. J. Mack, None

    R. Karim, None

    B. Weiser, None

    H. Burger, None

    M. H. Kuniholm, None

    B. Edlin, None

    C. Liu, None

    M. G. Peters, None

    A. French, None

    E. T. Golub, None

    G. B. Sharp, None

    A. Kovacs, None

    Findings in the abstracts are embargoed until 12:01 a.m. PST, Oct. 2nd with the exception of research findings presented at the IDWeek press conferences.