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

Abstract

OBJECTIVESAnemia 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.\n\nDESIGNRetrospective cohort study.\n\nSETTINGU.S.-based prospective clinical cohort of PLWH aged 18 and above receiving care at 8 sites between 1/2010-3/2018.\n\nPARTICIPANTS16,505 PLWH were included in this study.\n\nMAIN OUTCOME MEASURESAnemia 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.\n\nRESULTSDuring 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.\n\nCONCLUSIONThese 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.\n\nStrengths and limitations of this studyO_LIThis study utilized a large and geographically diverse population of PLWH in care across the U.S.\nC_LIO_LIThis study leveraged comprehensive clinical data, including information on diagnoses, medication use, laboratory test results, demographic information, and medical history.\nC_LIO_LIThis study investigated associations between specific types of ART core regimens and anemia risk.\nC_LIO_LIThis observational study is subject to residual confounding.\nC_LIO_LIThis 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.\nC_LI