Antiretroviral drug class and anaemia risk in the current treatment era among people living with HIV in the USA: a clinical cohort study

Barbara N. Harding; Bridget M. Whitney; Robin M. Nance; Heidi M. Crane; Greer Burkholder; Richard D. Moore; W. Christopher Mathews; Joseph J. Eron; Peter W. Hunt; Paul Volberding; Benigno Rodriguez; Kenneth Mayer; Michael S. Saag; Mari M. Kitahata; Susan R. Heckbert; Joseph A.C. Delaney

doi:10.1136/bmjopen-2019-031487

Antiretroviral drug class and anaemia risk in the current treatment era among people living with HIV in the USA: a clinical cohort study

Barbara N. Harding, Bridget M. Whitney, Robin M. Nance, Heidi M. Crane, Greer Burkholder, Richard D. Moore, W. Christopher Mathews, Joseph J. Eron, Peter W. Hunt, Paul Volberding, Benigno Rodriguez, Kenneth Mayer, Michael S. Saag, Mari M. Kitahata, Susan R. Heckbert, Joseph A.C. Delaney

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

OBJECTIVE: Anaemia 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 anaemia is limited. The objective was to compare the associations between anaemia incidence or haemoglobin change with core ART classes in the current ART era. DESIGN: Retrospective cohort study. SETTING: USA-based prospective clinical cohort of PLWH aged 18 and above receiving care at eight sites between January 2010 and March 2018. PARTICIPANTS: 16 505 PLWH were included in this study. MAIN OUTCOME MEASURES: Anaemia risk and haemoglobin change were estimated among PLWH for person-time on a protease inhibitor (PI) or an integrase strand transfer inhibitor (INSTI)-based regimen, relative to a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based reference. We also examined PLWH on regimens containing multiple core classes. Cox proportional hazards regression analyses were conducted to measure the associations between time-updated ART classes and incident anaemia or severe anaemia. Linear mixed effects models were used to examine the relationships between ART classes and haemoglobin change. RESULTS: During a median of 4.9 years of follow-up, 1040 developed anaemia and 488 developed severe anaemia. Compared with NNRTI use, INSTI-based regimens were associated with an increased risk of anaemia (adjusted HR (aHR) 1.26, 95% CI 1.00 to 1.58) and severe anaemia (aHR 1.51, 95% CI 1.07 to 2.11) and a decrease in haemoglobin level. Time on multiple core classes was also associated with increased anaemia risk (aHR 1.39, 95% CI 1.13 to 1.70), while no associations were found for PI use. CONCLUSION: These findings suggest INSTI use may increase the risk of anaemia. If confirmed, screening for anaemia development in users of INSTIs may be beneficial. Further research into the underlying mechanisms is warranted.

Original language	English (US)
Pages (from-to)	e031487
Journal	BMJ open
Volume	10
Issue number	3
DOIs	https://doi.org/10.1136/bmjopen-2019-031487
State	Published - Mar 19 2020

Keywords

HIV & AIDS
anaemia
antiretroviral therapy
cohort
integrase inhibitors

ASJC Scopus subject areas

General Medicine

Access to Document

10.1136/bmjopen-2019-031487

Cite this

Harding, B. N., Whitney, B. M., Nance, R. M., Crane, H. M., Burkholder, G., Moore, R. D., Mathews, W. C., Eron, J. J., Hunt, P. W., Volberding, P., Rodriguez, B., Mayer, K., Saag, M. S., Kitahata, M. M., Heckbert, S. R., & Delaney, J. A. C. (2020). Antiretroviral drug class and anaemia risk in the current treatment era among people living with HIV in the USA: a clinical cohort study. BMJ open, 10(3), e031487. https://doi.org/10.1136/bmjopen-2019-031487

Harding, BN, Whitney, BM, Nance, RM, Crane, HM, Burkholder, G, Moore, RD, Mathews, WC, Eron, JJ, Hunt, PW, Volberding, P, Rodriguez, B, Mayer, K, Saag, MS, Kitahata, MM, Heckbert, SR & Delaney, JAC 2020, 'Antiretroviral drug class and anaemia risk in the current treatment era among people living with HIV in the USA: a clinical cohort study', BMJ open, vol. 10, no. 3, pp. e031487. https://doi.org/10.1136/bmjopen-2019-031487

@article{7b85fbc980c14000b40aab210d70d6be,

title = "Antiretroviral drug class and anaemia risk in the current treatment era among people living with HIV in the USA: a clinical cohort study",

abstract = "OBJECTIVE: Anaemia 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 anaemia is limited. The objective was to compare the associations between anaemia incidence or haemoglobin change with core ART classes in the current ART era. DESIGN: Retrospective cohort study. SETTING: USA-based prospective clinical cohort of PLWH aged 18 and above receiving care at eight sites between January 2010 and March 2018. PARTICIPANTS: 16 505 PLWH were included in this study. MAIN OUTCOME MEASURES: Anaemia risk and haemoglobin change were estimated among PLWH for person-time on a protease inhibitor (PI) or an integrase strand transfer inhibitor (INSTI)-based regimen, relative to a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based reference. We also examined PLWH on regimens containing multiple core classes. Cox proportional hazards regression analyses were conducted to measure the associations between time-updated ART classes and incident anaemia or severe anaemia. Linear mixed effects models were used to examine the relationships between ART classes and haemoglobin change. RESULTS: During a median of 4.9 years of follow-up, 1040 developed anaemia and 488 developed severe anaemia. Compared with NNRTI use, INSTI-based regimens were associated with an increased risk of anaemia (adjusted HR (aHR) 1.26, 95% CI 1.00 to 1.58) and severe anaemia (aHR 1.51, 95% CI 1.07 to 2.11) and a decrease in haemoglobin level. Time on multiple core classes was also associated with increased anaemia risk (aHR 1.39, 95% CI 1.13 to 1.70), while no associations were found for PI use. CONCLUSION: These findings suggest INSTI use may increase the risk of anaemia. If confirmed, screening for anaemia development in users of INSTIs may be beneficial. Further research into the underlying mechanisms is warranted.",

keywords = "HIV & AIDS, anaemia, antiretroviral therapy, cohort, integrase inhibitors",

author = "Harding, {Barbara N.} and Whitney, {Bridget M.} and Nance, {Robin M.} and Crane, {Heidi M.} and Greer Burkholder and Moore, {Richard D.} and Mathews, {W. Christopher} and Eron, {Joseph J.} and Hunt, {Peter W.} and Paul Volberding and Benigno Rodriguez and Kenneth Mayer and Saag, {Michael S.} and Kitahata, {Mari M.} and Heckbert, {Susan R.} and Delaney, {Joseph A.C.}",

note = "Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.",

year = "2020",

month = mar,

day = "19",

doi = "10.1136/bmjopen-2019-031487",

language = "English (US)",

volume = "10",

pages = "e031487",

journal = "BMJ open",

issn = "2044-6055",

publisher = "BMJ Publishing Group",

number = "3",

}

TY - JOUR

T1 - Antiretroviral drug class and anaemia risk in the current treatment era among people living with HIV in the USA

T2 - a clinical cohort study

AU - Harding, Barbara N.

AU - Whitney, Bridget M.

AU - Nance, Robin M.

AU - Crane, Heidi M.

AU - Burkholder, Greer

AU - Moore, Richard D.

AU - Mathews, W. Christopher

AU - Eron, Joseph J.

AU - Hunt, Peter W.

AU - Volberding, Paul

AU - Rodriguez, Benigno

AU - Mayer, Kenneth

AU - Saag, Michael S.

AU - Kitahata, Mari M.

AU - Heckbert, Susan R.

AU - Delaney, Joseph A.C.

PY - 2020/3/19

Y1 - 2020/3/19

N2 - OBJECTIVE: Anaemia 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 anaemia is limited. The objective was to compare the associations between anaemia incidence or haemoglobin change with core ART classes in the current ART era. DESIGN: Retrospective cohort study. SETTING: USA-based prospective clinical cohort of PLWH aged 18 and above receiving care at eight sites between January 2010 and March 2018. PARTICIPANTS: 16 505 PLWH were included in this study. MAIN OUTCOME MEASURES: Anaemia risk and haemoglobin change were estimated among PLWH for person-time on a protease inhibitor (PI) or an integrase strand transfer inhibitor (INSTI)-based regimen, relative to a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based reference. We also examined PLWH on regimens containing multiple core classes. Cox proportional hazards regression analyses were conducted to measure the associations between time-updated ART classes and incident anaemia or severe anaemia. Linear mixed effects models were used to examine the relationships between ART classes and haemoglobin change. RESULTS: During a median of 4.9 years of follow-up, 1040 developed anaemia and 488 developed severe anaemia. Compared with NNRTI use, INSTI-based regimens were associated with an increased risk of anaemia (adjusted HR (aHR) 1.26, 95% CI 1.00 to 1.58) and severe anaemia (aHR 1.51, 95% CI 1.07 to 2.11) and a decrease in haemoglobin level. Time on multiple core classes was also associated with increased anaemia risk (aHR 1.39, 95% CI 1.13 to 1.70), while no associations were found for PI use. CONCLUSION: These findings suggest INSTI use may increase the risk of anaemia. If confirmed, screening for anaemia development in users of INSTIs may be beneficial. Further research into the underlying mechanisms is warranted.

AB - OBJECTIVE: Anaemia 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 anaemia is limited. The objective was to compare the associations between anaemia incidence or haemoglobin change with core ART classes in the current ART era. DESIGN: Retrospective cohort study. SETTING: USA-based prospective clinical cohort of PLWH aged 18 and above receiving care at eight sites between January 2010 and March 2018. PARTICIPANTS: 16 505 PLWH were included in this study. MAIN OUTCOME MEASURES: Anaemia risk and haemoglobin change were estimated among PLWH for person-time on a protease inhibitor (PI) or an integrase strand transfer inhibitor (INSTI)-based regimen, relative to a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based reference. We also examined PLWH on regimens containing multiple core classes. Cox proportional hazards regression analyses were conducted to measure the associations between time-updated ART classes and incident anaemia or severe anaemia. Linear mixed effects models were used to examine the relationships between ART classes and haemoglobin change. RESULTS: During a median of 4.9 years of follow-up, 1040 developed anaemia and 488 developed severe anaemia. Compared with NNRTI use, INSTI-based regimens were associated with an increased risk of anaemia (adjusted HR (aHR) 1.26, 95% CI 1.00 to 1.58) and severe anaemia (aHR 1.51, 95% CI 1.07 to 2.11) and a decrease in haemoglobin level. Time on multiple core classes was also associated with increased anaemia risk (aHR 1.39, 95% CI 1.13 to 1.70), while no associations were found for PI use. CONCLUSION: These findings suggest INSTI use may increase the risk of anaemia. If confirmed, screening for anaemia development in users of INSTIs may be beneficial. Further research into the underlying mechanisms is warranted.

KW - HIV & AIDS

KW - anaemia

KW - antiretroviral therapy

KW - cohort

KW - integrase inhibitors

UR - http://www.scopus.com/inward/record.url?scp=85082092561&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85082092561&partnerID=8YFLogxK

U2 - 10.1136/bmjopen-2019-031487

DO - 10.1136/bmjopen-2019-031487

M3 - Article

C2 - 32198297

AN - SCOPUS:85082092561

SN - 2044-6055

VL - 10

SP - e031487

JO - BMJ open

JF - BMJ open

IS - 3

ER -

Antiretroviral drug class and anaemia risk in the current treatment era among people living with HIV in the USA: a clinical cohort study

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this