title: Prognostic implications of baseline anaemia and changes in haemoglobin concentrations with amphotericin B therapy for cryptococcal meningitis.
abstract: Anaemia represents a common toxicity with amphotericin B-based induction therapy in HIV-infected persons with cryptococcal meningitis. We sought to examine the impact of amphotericin-related anaemia on survival.
  
  
  
  We used data from Ugandan and South African trial participants to characterize the variation of haemoglobin concentrations from diagnosis to 12 weeks post-diagnosis. Anaemia severity was classified based on the haemoglobin concentration at cryptococcal meningitis diagnosis, and nadir haemoglobin values during amphotericin induction. Cox proportional hazard models were used to estimate 2- and 10-week mortality risk. We also estimated 10-week mortality risk among participants with nadir haemoglobin < 8.5 g/dL during amphotericin induction and who survived ≥ 2 weeks post-enrolment.
  
  
  
  The median haemoglobin concentration at meningitis diagnosis was 11.5 g/dL [interquartile range (IQR) 9.7-13 g/dL; n = 311] with a mean decline of 4.2 g/dL [95% confidence interval (CI) -4.6 to -3.8; P < 0.001; n = 148] from diagnosis to nadir value among participants with baseline haemoglobin ≥ 8.5 g/dL. The median haemoglobin concentration was 8.1 g/dL (IQR 6.5-9.5 g/dL) at 2 weeks, increasing to 9.4 g/dL (IQR 8.2-10.9 g/dL) by 4 weeks and continuing to increase to 12 weeks. Among participants with haemoglobin < 8.5 g/dL at diagnosis, mortality risk was elevated at 2 weeks [hazard ratio (HR) 2.7; 95% CI 1.5-4.9; P < 0.01] and 10 weeks (HR 1.8; 95% CI 1.1-2.2; P = 0.03), relative to those with haemoglobin ≥ 8.5 g/dL. New-onset anaemia occurring with amphotericin therapy did not have a statistically significant association with 10-week mortality (HR 2.0; 95% CI 0.5-9.1; P = 0.4).
  
  
  
  Amphotericin induced significant haemoglobin declines, which were mostly transient and did not impact 10-week mortality. Individuals with moderate to life-threatening anaemia at baseline had a higher mortality risk at 2 and 10 weeks post-enrolment.
authors.affiliation: Infectious Disease Institute, Makerere University, Kampala, Uganda.
authors.forename: L
authors.initials: L
authors.lastname: Tugume
authors.affiliation: Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.|Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
authors.forename: B M
authors.identifier: 0000-0003-1655-6006
authors.initials: BM
authors.lastname: Morawski
authors.affiliation: Infectious Disease Institute, Makerere University, Kampala, Uganda.|Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: M
authors.initials: M
authors.lastname: Abassi
authors.affiliation: Infectious Disease Institute, Makerere University, Kampala, Uganda.|Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.|Center for Infectious Diseases & Microbiology Translational Research, University of Minnesota, Minneapolis, MN, USA.
authors.forename: N C
authors.initials: NC
authors.lastname: Bahr
authors.affiliation: Infectious Disease Institute, Makerere University, Kampala, Uganda.
authors.forename: R
authors.initials: R
authors.lastname: Kiggundu
authors.affiliation: Infectious Disease Institute, Makerere University, Kampala, Uganda.
authors.forename: H W
authors.initials: HW
authors.lastname: Nabeta
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
authors.forename: K H
authors.initials: KH
authors.lastname: Hullsiek
authors.affiliation: Department of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda.
authors.forename: K
authors.initials: K
authors.lastname: Taseera
authors.affiliation: Infectious Disease Institute, Makerere University, Kampala, Uganda.|Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Musubire
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine and Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: C
authors.initials: C
authors.lastname: Schutz
authors.affiliation: Department of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda.
authors.forename: C
authors.initials: C
authors.lastname: Muzoora
authors.affiliation: Infectious Disease Institute, Makerere University, Kampala, Uganda.|Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Williams
authors.affiliation: Epidemiologic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Rolfes
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine and Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.|Department of Medicine, Imperial College London, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Meintjes
authors.affiliation: Infectious Disease Institute, Makerere University, Kampala, Uganda.|Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: J
authors.identifier: 0000-0002-0480-9646
authors.initials: J
authors.lastname: Rhein
authors.affiliation: Infectious Disease Institute, Makerere University, Kampala, Uganda.|Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.|Department of Medicine, Faculty of Health Sciences, Makerere University, Kampala, Uganda.
authors.forename: D B
authors.initials: DB
authors.lastname: Meya
authors.affiliation: Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.|Center for Infectious Diseases & Microbiology Translational Research, University of Minnesota, Minneapolis, MN, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Boulware
mesh_terms: D000293:Adolescent; D000328:Adult; D000666:Amphotericin B / Q000627:therapeutic use*; D000740:Anemia / Q000473:pathology*; D000935:Antifungal Agents / Q000627:therapeutic use*; D005260:Female; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D008297:Male; D016919:Meningitis, Cryptococcal / Q000150:complications* / Q000188:drug therapy*; D008875:Middle Aged; D013019:South Africa; D016019:Survival Analysis; D016896:Treatment Outcome; D014454:Uganda; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D006454:Hemoglobins; D000666:Amphotericin B
keywords: 
  HIV
  ; amphotericin B; anaemia; cryptococcal meningitis