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

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.

journal_name

HIV Med

journal_title

HIV medicine

authors

Tugume L,Morawski BM,Abassi M,Bahr NC,Kiggundu R,Nabeta HW,Hullsiek KH,Taseera K,Musubire AK,Schutz C,Muzoora C,Williams DA,Rolfes MA,Meintjes G,Rhein J,Meya DB,Boulware DR

doi

10.1111/hiv.12387

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

13-20

issue

eissn

1464-2662

issn

1468-1293

journal_volume

pub_type

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