Abstract

Impaired hematologic status (IHS) was investigated as a determinant of immune function defined as cluster of differentiation 4 (CD4) T-helper cell count, quality of life (QOL) weight and hospitalization/mortality over 18-months among 398 adult persons living with HIV/AIDS (PLWHA) on anti-retroviral therapy. IHS was defined as having anemia at baseline (Hemoglobin: <12 g/dL for women and <13 g/dL for men), time-updated anemia or having low (<30 μg/L) or high (>200 μg/L for men and >150 μg/L for women) ferritin levels at baseline. Months-to-hospitalization/death or study-end (if no event) was calculated from enrollment. Multivariable linear-mixed models quantified associations between IHS and changes in CD4 cell-count, weight gain and QOL. Cox proportional hazards models calculated hazard ratios (HR) and corresponding 95% confidence intervals (CI) for IHS-related differences in time-to-hospitalization/death. The prevalences of anemia and high and low ferritin levels at baseline were 48.7% (n = 194), 40.5% (n = 161) and 17% (n = 68), respectively. Most patients (63.4%, n = 123) remained anemic during follow-up. Weight gained (ferritin-time interaction, p < 0.01) and QOL (anemia-time interaction, p = 0.05; ferritin-time interaction, p = 0.01) were lower for PLWHA with versus without IHS. Relative to anemia-free/normal ferritin, the risk of hospitalization/death was elevated for PLWHA with anemia (HR = 2.0; 95% CI: 1.2–3.6), low or high ferritin (HR: 1.8–1.9, 95% CI: 0.9–4.1) and those that developed new/persistent/progressive anemia (HR: 2.3–6.7, 95% CI: 1.0–12.7). Among PLWHA, IHS predicted deficits in QOL, low weight gain and a high risk of hospitalization/death. Intervention to mitigate persistent IHS may be warranted among PLWHA on long-term highly active antiretroviral therapy (HAART) to improve health outcomes.

Highlights

  • Impaired hematologic status (IHS)—including anemia and high or low ferritin—remains highly prevalent in chronic HIV despite highly active antiretroviral therapy (HAART) [1,2,3]

  • We extend current knowledge base by providing novel empirical data on the adverse impact of persistent anemia on immune recovery, hospitalization and mortality

  • We show that resolution of baseline anemia was associated with comparable immune recovery, quality of life (QOL) and risk of hospitalization/death over 18 months relative to persons living with HIV/AIDS (PLWHA) anemia free throughout

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Summary

Introduction

Impaired hematologic status (IHS)—including anemia and high or low ferritin—remains highly prevalent in chronic HIV despite highly active antiretroviral therapy (HAART) [1,2,3]. HIV infection leads to IHS through multiple mechanisms including the HIV-1 Nef protein increasing intra-macrophagic iron accumulation [4] and perturbation of acute phase proteins/hormones such as hepcidin, which regulates iron thirst in macrophages [5,6,7]. The dynamic interactions between HIV and iron create a positive feedback loop that increases the risk of iron overload, onset and persistence of non-iron deficiency anemia and may partly mediate HIV viral persistence and rebound despite HAART [8,10,11]. Persistent immune activation typical in HIV infection contributes to anemia of chronic disease (ACD) [12]. Regardless of etiology, is associated with sub-optimal immune recovery [13] and mortality [14] in persons living with HIV/AIDS (PLWHA)

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