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THE ASSOCIATION OF ANEMIA WITH SURVIVAL AMONG PEOPLE WITH HIV FOLLOWING ANTIRETROVIRAL INITIATION IN THE NA-ACCORD 2007-2016
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Abstract
Background:
Anemia is an independent predictor of mortality, which may be utilized as a signal of deteriorating health. We estimated the association between anemia severity categories and mortality following the initiation of antiretroviral therapy (ART) among people with HIV (PWH) in North America.
Methods:
Within the NA-ACCORD, annual median hemoglobin measurements between 01/01/2007-12/31/2016 were categorized using World Health Organization criteria into mild (11.0-12.9g/dL men, 11.0-11.9g/dL women), moderate (8.0–10.9g/dL men/women) and severe (<8.0g/dL men/women) anemia. Discrete time-to-event analyses using complementary log-log link models estimated mortality hazards ratios adjusted for demographics, comorbidities, and HIV clinical markers with 95% confidence intervals for the association between anemia and mortality.
Results:
Among 67,228 PWH contributing a total of 320,261 annual median hemoglobin measurements, 257,293 (80%) demonstrated no anemia, 44,041 (14%) mild, 18,259 (6%) moderate, and 668 (0.2%) severe anemia during follow-up. Mortality risk was 5.6-fold higher among PWH with (vs. without) anemia. The association was greater among males (aHR=5.8 [5.4, 6.2]) versus females (aHR=4.1 [3.2, 5.4]). Mortality risk was 3.8-fold higher among PWH with mild anemia, 13.7-fold higher with moderate anemia, and 34.5-fold higher with severe anemia (vs. no anemia). Median hemoglobin levels significantly declined within 4 years prior to death, with the maximum decrease the year prior to death. Macrocytic anemia was associated with an increased and microcytic anemia a decreased mortality risk (vs. normocytic anemia).
Males with HIV and anemia had a higher risk of mortality across all anemia severity categories when compared with females. Younger females likely have a higher prevalence of anemia because of blood loss through menses, typically leading to iron deficiency which decreases following menopause18. In contrast, anemia among men is not related to a physiologic process but instead likely reflects underlying pathology 28. Therefore, the difference in mortality outcomes may be because of the underlying etiology of anemia being different between men and women, which is also identified through mortality differences in age categories by sex. This association may in part also explain the difference in mortality risk by MCV categories of anemia as the most common cause of microcytic anemia is iron deficiency which is more prevalent among menstruating females39. However, as anemia was significantly associated with all-cause mortality among both males and females, identification of anemia should prompt clinicians to investigate the underlying cause, specifically if the anemia is moderate/severe or progressive.
Conclusions:
Anemia among PWH who have initiated ART is an important predictive marker for mortality with macrocytic anemia having an increased and microcytic anemia a decreased association with mortality compared with normocytic anemia.
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