Prognostic implications of baseline anaemia and changes in haemoglobin concentrations with amphotericin B therapy for cryptococcal meningitis

L. Tugume, Bm Morawski, M. Abassi, Nc Bahr, R. Kiggundu, Hw Nabeta, Kh Hullsiek, K. Taseera, Ak Musubire, C. Schutz, C. Muzoora, Da Williams, Ma Rolfes, G. Meintjes, J. Rhein, Db Meya, Dr Boulware

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Objectives: 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. Methods: 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. Results: 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). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)13-20
Number of pages8
JournalHIV Medicine
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2017

Bibliographical note

Funding Information:
This work was supported by the National Institute of Neurologic Disorders and Stroke, the National Institute of Allergy and Infectious Disease, and the Fogarty International Center at the National Institutes of Health (U01AI089244, R01NS086312, T32AI055433 and R25TW-009345). The authors wish to thank Drs Paul Bohjanen and Andrew Kambugu for support and input. We also thank Dr Ali El Bireer and the laboratory staff at Makerere University Johns Hopkins University Laboratory in Kampala as well as Mr Richard Kwizera for phlebotomy.

Publisher Copyright:
© 2016 British HIV Association

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • HIV
  • amphotericin B
  • anaemia
  • cryptococcal meningitis

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