2157. Risk of Acute Liver Injury with Modern Antiretroviral Therapy
Session: Poster Abstract Session: HIV/HCV Coinfection and Liver Disease
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • ARV_ALI_IDWeek Poster #2157.pdf (591.1 kB)
  • Background: The hepatic safety of modern antiretroviral therapy (ART) regimens has not been thoroughly evaluated. We determined the risk of acute liver injury (ALI) for antiretroviral components, classes, and currently used regimens to assess their comparative hepatic safety.

    Methods: We conducted a cohort study in 10,083 HIV+ persons initiating ART in Kaiser Permanente Northern California (n=2,099) from 2004-2010 and the Veterans Aging Cohort Study (n=7,984) from 2004-2012. Within the first year of ART, we determined occurrence of: 1) liver aminotransferases >200 U/L, and 2) severe ALI (coagulopathy and jaundice within 30 days of each other). We used Cox regression to determine hazard ratios (HRs) and 95% confidence intervals of endpoints among users of: 1) different nucleos(t)ide reverse transcriptase inhibitor (NRTI) backbones, 2) protease inhibitor (PI), integrase strand transfer inhibitors (INSTI), and non-NRTI classes, and 3) currently used ART regimens. The most commonly prescribed drug or regimen was the reference.

    Results: After adjustment for viral hepatitis and baseline aminotransferase, the rate of liver aminotransferases >200 U/L was similar for abacavir/lamivudine versus tenofovir/emtricitabine (TDF/FTC; HR, 0.86 [0.56-1.60]). Compared to non-NRTI users, adjusted rates of liver aminotransferases >200 U/L were higher for initiators of a PI (HR, 1.39 [1.04-1.86]) or INSTI-based regimen (HR, 1.81 [0.77-4.22]), though the latter comparison did not reach statistical significance. Rates of liver aminotransferases >200 U/L were higher for initiators of raltegravir+TDF/FTC (HR, 2.00; [0.85-4.72]), atazanavir+TDF/FTC (HR, 1.48 [0.95-2.30]), and darunavir +TDF/FTC (HR, 1.42 [0.60-3.38] compared to efavirenz+TDF/FTC initiators but were not statistically significant. Severe ALI was too rare to evaluate in adjusted analyses.

    Conclusion: PI use was associated with higher rates of liver aminotransferase elevations, but severe ALI was uncommon with all regimens.

    Charitha Gowda, MD1,2,3, Craig W. Newcomb, MS2, Qing Liu, MD2, Dena M. Carbonari, MS2,3, James D. Lewis, MD, MSCE2,3,4, Kimberly Forde, MD, MHS2,3,4, David S. Goldberg, MD, MSCE2,3, K. Rajender Reddy, MD3,4, Jason Roy, PhD2,3, Amy R. Marks, MPH5, Jennifer L. Schneider, MPH5, Jay R. Kostman, MD6, Douglas Corley, MD, PhD5, Janet P. Tate, ScD7,8, Amy C. Justice, MD, PhD7,8 and Vincent Lo Re III, MD, MSCE1,2,3, (1)Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, (2)Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, (3)Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, (4)Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, (5)Division of Research, Kaiser Permanente Northern California, Oakland, CA, (6)Jonathan Lax Treatment Center, Philadelphia FIGHT, Philadelphia, PA, (7)Yale University School of Medicine, New Haven, CT, (8)VA Connecticut Healthcare System, West Haven, CT

    Disclosures:

    C. Gowda, None

    C. W. Newcomb, None

    Q. Liu, None

    D. M. Carbonari, None

    J. D. Lewis, Centocor: Grant Investigator , Research grant
    Amgen: Consultant , Consulting fee
    Millennium Pharmaceuticals: Consultant , Consulting fee
    Pfizer: Consultant , Consulting fee

    K. Forde, None

    D. S. Goldberg, None

    K. R. Reddy, Abbott: Grant Investigator , Research grant
    Anadys: Grant Investigator , Research grant
    Bristol-Myers Squibb: Consultant and Grant Investigator , Consulting fee and Research grant
    Genetech-Roche: Consultant and Grant Investigator , Consulting fee and Research grant
    Gilead Sciences: Consultant and Grant Investigator , Consulting fee and Research grant
    Merck: Consultant and Grant Investigator , Consulting fee and Research grant
    Ikaria: Grant Investigator , Research grant
    Janssen: Consultant and Grant Investigator , Consulting fee and Research grant
    Vertex: Consultant and Grant Investigator , Consulting fee and Research grant
    Idenix: Consultant , Consulting fee
    American Liver Foundation: Scientific Advisor , Consulting fee
    ViralEd: Development of educational materials , Speaker honorarium

    J. Roy, None

    A. R. Marks, None

    J. L. Schneider, None

    J. R. Kostman, Gilead Sciences: Scientific Advisor , Consulting fee

    D. Corley, Pfizer: Grant Investigator , Research grant

    J. P. Tate, None

    A. C. Justice, None

    V. Lo Re III, AstraZeneca: Grant Investigator , Research grant
    Gilead Sciences: Grant Investigator , Research grant

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