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Class of antiretroviral drugs and anemia risk in the current treatment era

By Barbara N Harding, B.M. Whitney, R.M. Nance, H.M. Crane, G. Burkholder, R.D. Moore, W.C. Mathews, J.J. Eron, P.W. Hunt, P. Volberding, B. Rodriguez, K.H. Mayer, M.S. Saag, M.M. Kitahata, S.R. Heckbert, J.A.C. Delaney

Posted 21 Jun 2019
bioRxiv DOI: 10.1101/674549

OBJECTIVES: Anemia is common among people living with HIV (PLWH) and has been associated with certain, often older, antiretroviral medications. Information on current antiretroviral therapy (ART) and anemia is limited. The objectives were to compare associations between anemia incidence or hemoglobin change with core ART classes in the current ART era. DESIGN: Retrospective cohort study. SETTING: U.S.-based prospective clinical cohort of PLWH aged 18 and above receiving care at 8 sites between 1/2010-3/2018. PARTICIPANTS: 16,505 PLWH were included in this study. MAIN OUTCOME MEASURES: Anemia risk and hemoglobin change were measured for person-time on a protease inhibitor (PI) or an integrase strand transfer inhibitor (INSTI), relative to a non-nucleoside reverse transcriptase inhibitor (NNRTI) reference. We also examined PLWH on multiple core classes. Cox proportional hazards regression analyses were conducted to measure associations between time-updated ART classes and incident anemia or severe anemia. Linear mixed effects models were used to examine relationships between ART classes and hemoglobin change. RESULTS: During a median of 4.9 years of follow-up, 1,040 developed anemia and 488 developed severe anemia during. Compared to NNRTI use, INSTI-based regimens were associated with an increased risk of anemia (adjusted hazard ratio [aHR] 1.17, 95% confidence interval [CI] 0.94-1.47) and severe anemia (aHR1.55 95%CI 1.11-2.17), and a decrease in hemoglobin level. Time on multiple core classes was also associated with increased anemia risk (aHR 1.30, 95%CI 1.06-1.60) and severe anemia risk (aHR 1.35, 95%CI 0.99-1.85), while no associations were found for PI use. CONCLUSION: These findings suggest INSTI use may increase the risk of anemia. If confirmed, screening for anemia development in users of INSTIs may be beneficial. Further research into underlying mechanisms is warranted.

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