1688. Development of Anemia and Changes in Hemoglobin Concentrations with Amphotericin B Therapy for Cryptococcal Meningitis
Session: Poster Abstract Session: HIV: Other Opportunistic Infections in HIV
Saturday, October 10, 2015
Room: Poster Hall
  • Poster_Anemia and Amphotericin.pdf (975.7 kB)
  • Background:

    The WHO recommends amphotericin B as a central component of induction therapy for HIV-associated cryptococcal meningitis. Severe anemia represents a significant toxicity of amphotericin in individuals with cryptococcal meningitis. The impact of amphotericin-related anemia on mortality in such individuals has not been widely studied.


    Hemoglobin concentration was measured in cryptococcal meningitis patients enrolled in the COAT (ClinicalTrials.gov: NCT01075152) or ASTRO (ClinicalTrials.gov: NCT01802385) trials. Anemia severity was classified per DAIDS (2009) criteria. We characterized hemoglobin concentrations from diagnosis to 12 weeks post-diagnosis. Cox proportional hazard models estimated 2- and 10-week mortality risk in patients with hemoglobin <=8.4g/dl at diagnosis, versus those with hemoglobin >=8.5g/dl. Cox proportional hazard models estimated 10-week mortality risk among participants who experienced nadir hemoglobin levels <=8.4g/dl after amphotericin initiation and survived at least 2 weeks post-enrollment.


    Among COAT trial participants with hemoglobin >=8.5g/dl at diagnosis, hemoglobin the mean decline from diagnosis to nadir was 4.2g/dl (95%CI, 3.8 -4.6; P<0.001; n=148); there was an increase of 2.4g/dl (95%CI, 1.4 - 3.3; P<0.001; n=130) in hemoglobin from the end of induction to 12 weeks post diagnosis (Fig. 1). Changes in hemoglobin concentrations were similar across sex. For persons from the COAT and ASTRO trials with a hemoglobin of <=8.4g/dl at diagnosis, the hazard ratio for 2-week mortality was 2.21 (95%CI, 1.22-4.01; P=0.01), and for 10-week mortality, the hazard ratio was 1.70 (95%CI, 1.01-2.84; P=0.04), relative to those with >8.4g/dl (Fig. 2). Amphotericin induced anemia during induction had no impact on 10-week mortality (HR=1.40, 95%CI, 0.73-2.70; P=0.32).


    Individuals undergoing amphotericin-based induction therapy in COAT experienced a mean hemoglobin decline of 4.2g/dl, which did not impact 10-week mortality. The hemoglobin change was mostly transient and increased by 2.4g/dl from the end of induction to 12 weeks post diagnosis. Individuals with moderate to life-threatening anemia at baseline had a higher risk of death at 2- and 10-weeks post-diagnosis.

    Lillian Tugume, MBChB1, Bozena Morawski, MPH2,3, Mahsa Abassi, DO1,3, Nathan Bahr, MD MA1,3,4, Reuben Kiggundu, MBChB1, Henry Nabeta, MBChB1, Kathy Huppler Hullsiek, PhD5, Taseera Kabanda, MBChB, MSc6, Abdu Musubire, MMed1, Charlotte Schutz, MPH7, Conrad Muzoora, MMed8, Darlisha Williams, MPH1,3, Melissa Rolfes, PhD MPH3, Graeme Meintjes, MBChB, FCP, MRCP, DipHIVMan, PhD7,9, Joshua Rhein, MD1,3, David Meya, MMed1,3,4,10, David Boulware, MD, MPH3,4 and COAT Trial and ASTRO-CM Trial Teams, (1)Infectious Disease Institute, Makerere University, Kampala, Uganda, (2)Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, (3)Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, (4)Center for Infectious Diseases & Microbiology Translational Research, University of Minnesota, Minneapolis, MN, (5)Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, (6)Department of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda, (7)Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa, (8)Mbarara University of Science and Technology, Mbarara, Uganda, (9)Department of Medicine, Imperial College London, London, England, (10)Department of Medicine, Faculty of Health Sciences, Makerere University, Kampala, Uganda


    L. Tugume, None

    B. Morawski, None

    M. Abassi, None

    N. Bahr, None

    R. Kiggundu, None

    H. Nabeta, None

    K. H. Hullsiek, None

    T. Kabanda, None

    A. Musubire, None

    C. Schutz, None

    C. Muzoora, None

    D. Williams, None

    M. Rolfes, None

    G. Meintjes, None

    J. Rhein, None

    D. Meya, None

    D. Boulware, None

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 7th with the exception of research findings presented at the IDWeek press conferences.