Abstract
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.
Strengths and limitations of this study
This study utilized a large and geographically diverse population of PLWH in care across the U.S.
This study leveraged comprehensive clinical data, including information on diagnoses, medication use, laboratory test results, demographic information, and medical history.
This study investigated associations between specific types of ART core regimens and anemia risk.
This observational study is subject to residual confounding.
This study focused on anemia assessed from hemoglobin lab values taken at regular medical care visits without excluding participants with conditions strongly associated with hemoglobin level through non-traditional HIV mechanisms.
Footnotes
Competing interest statement: Ms. Harding reports grants from NHLBI during the conduct of the study; Ms. Whitney reports grants from NIH during the conduct of the study; Ms. Nance reports grants from NIH during the conduct of the study; Dr. Crane reports grants from NHLBI during the conduct of the study, grants from NIH, grants from ViiV and grants from PCORI outside the submitted work; Dr. Burkholder reports grants from NIH during the conduct of the study, other from Amgen, Inc outside the submitted work; Dr. Moore reports grants from NHLBI during the conduct of the study; Dr. Mathews reports grants from NHLBI during the conduct of the study; Dr. Eron reports grants from National Institutes of Health, during the conduct of the study, grants and personal fees from Gilead Sciences, grants and personal fees from ViiV Healthcare, grants and personal fees from Janssen and personal fees from Merck outside the submitted work; Dr. Hunt reports grants from NHLBI during the conduct of the study, personal fees from Gilead, personal fees from Viiv, personal fees from Janssen and non-financial support from Merck outside the submitted work; Dr. Volberding reports grants from NHLBI during the conduct of the study, other from Merck outside the submitted work; Dr. Rodriguez reports grants from NIH during the conduct of the study, personal fees from Gilead and personal fees from ViiV outside the submitted work; Dr. Mayer reports grants from NHLBI during the conduct of the study; Dr. Saag reports grants from NIAID / NIH during the conduct of the study, grants from Gilead, Merck, and ViiV Healthcare outside the submitted work; Dr. Kitahata reports grants from NHLBI during the conduct of the study; Dr. Heckbert reports grants from National Institutes of Health during the conduct of the study; Dr. Delaney reports grants from NHLBI during the conduct of the study.
Ethical approval: Informed consent was obtained from all participants and institutional review boards at each site approved CNICS protocols.
Funding: This project was funded by R01HL126538-01A1/National Heart, Lung and Blood Institute. They provided an unrestricted grant and we are completely independent from the study sponsors.