학술논문
Incidence of Hypertension and Blood Pressure Changes in Persons With Human Immunodeficiency Virus at High Risk for Cardiovascular Disease Switching From Boosted Protease Inhibitors to Dolutegravir: A Post-hoc Analysis of the 96-week Randomised NEAT-022 Trial.
Document Type
Academic Journal
Author
Sempere A; Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.; Assoumou L; Département d'Epidémiologie, Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, Paris, France.; González-Cordón A; Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.; Waters L; Mortimer Market Centre, Central & North West London National Health Service (NHS) Foundation Trust, London, United Kingdom.; Rusconi S; Ospedale Luigi Sacco, Università degli Studi, Milano, Italy.; Domingo P; Mortimer Market Centre, Central & North West London National Health Service (NHS) Foundation Trust, London, United Kingdom.; Hospital de Sant Pau, Barcelona, Spain.; Gompels M; North Bristol NHS Trust, Bristol, United Kingdom.; de Wit S; Centre Hospitalier Universitaire Saint-Pierre, Brussels, Belgium.; Raffi F; Centre Hospitalier Universitaire, Nantes, France.; Stephan C; Universitätsklinikum-Infektionskrankheiten, Frankfurt, Germany.; Masiá M; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.; Hospital General Universitario de Elche, Elche, Spain.; Rockstroh J; Universitätsklinikum, Bonn, Germany.; Katlama C; Hôpital Universitaire Pitié Salpêtrière, Service des Maladies Infectieuses et Tropicales, France.; Behrens GMN; Medizinische Hochschule, Hannover, Germany.; Moyle G; Chelsea and Westminster Hospital NHS Foundation Trust, London, United Kingdom.; Johnson M; Royal Free London NHS Foundation Trust, London, United Kingdom.; Fox J; Guy's & St Thomas' NHS Foundation Trust, London, United Kingdom.; Stellbrink HJ; Infektionsmedizinisches Centrum, Hamburg, Germany.; Guaraldi G; University of Modena and Reggio Emilia, Modena, Italy.; Florence E; Universitair Ziekenhuis Antwerpen, Antwerp, Belgium.; Esser S; Universitätsklinikum, Universität Duisburg-Essen, Essen, Germany.; Gatell J; ViiV Healthcare, Barcelona, Spain.; Pozniak A; Chelsea and Westminster Hospital NHS Foundation Trust, London, United Kingdom.; Martínez E; Département d'Epidémiologie, Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, Paris, France.; Mortimer Market Centre, Central & North West London National Health Service (NHS) Foundation Trust, London, United Kingdom.
Source
Publisher: Oxford University Press Country of Publication: United States NLM ID: 9203213 Publication Model: Print Cited Medium: Internet ISSN: 1537-6591 (Electronic) Linking ISSN: 10584838 NLM ISO Abbreviation: Clin Infect Dis Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Integrase inhibitors have been recently linked to a higher risk for hypertension. In NEAT022 randomized trial, virologically suppressed persons with human immunodeficiency virus (HIV, PWH) with high cardiovascular risk switched from protease inhibitors to dolutegravir either immediately (DTG-I) or after 48 weeks (DTG-D).
Methods: Primary endpoint was incident hypertension at 48 weeks. Secondary endpoints were changes in systolic (SBP) and diastolic (DBP) blood pressure; adverse events and discontinuations associated with high blood pressure; and factors associated with incident hypertension.
Results: At baseline, 191 (46.4%) participants had hypertension and 24 persons without hypertension were receiving antihypertensive medications for other reasons. In the 197 PWH (n = 98, DTG-I arm; n = 99, DTG-D arm) without hypertension or antihypertensive agents at baseline, incidence rates per 100 person-years were 40.3 and 36.3 (DTG-I) and 34.7 and 52.0 (DTG-D) at 48 (P = .5755) and 96 (P = .2347) weeks. SBP or DBP changes did not differed between arms. DBP (mean, 95% confidence interval) significantly increased in both DTG-I (+2.78 mmHg [1.07-4.50], P = .0016) and DTG-D (+2.29 mmHg [0.35-4.23], P = .0211) arms in the first 48 weeks of exposure to dolutegravir. Four (3 under dolutegravir, 1 under protease inhibitors) participants discontinued study drugs due to adverse events associated with high blood pressure. Classical factors, but not treatment arm, were independently associated with incident hypertension.
Conclusions: PWH at high risk for cardiovascular disease showed high rates of hypertension at baseline and after 96 weeks. Switching to dolutegravir did not negatively impact on the incidence of hypertension or blood pressure changes relative to continuing protease inhibitors.
Competing Interests: Potential conflicts of interest. A. G.-C. has received honoraria for lectures (Gilead, Janssen, Merck, Sharp & Dohme [MSD], and ViiV), advisory boards (ViiV) or travel grants (Gilead, MSD, and ViiV) and her institution has received research grants from Gilead, Janssen, MSD, and ViiV; L. W. has received honoraria for lectures and consulting fees (Gilead, MSD, ViiV), advisory boards or travel grants from Gilead, Janssen, MSD, and ViiV; S. R. has received honoraria for lectures, advisory boards or travel grants from Gilead, Janssen, and ViiV. He also reports payment or honoraria from MSD and Theratechnologies; P. D. has received honoraria for lectures or advisory boards and his institution has received research grants from Gilead, Janssen, MSD and ViiV. He also reports consulting fees and payment or honoraria from Gilead Sicences, ViiV Healthcare, Jansen & Cilag, Merck, Sharp & Dohme, Roche, GSK; M. G. has received honoraria for lectures, advisory boards or travel grants from Gilead, MSD, and ViiV; F. R. has received honoraria for lectures (Gilead, Merck, and ViiV), advisory boards (Merck and ViiV) or travel grants (Gilead and ViiV) from Gilead, Janssen, MSD, Theratechnologies, and ViiV. He also reports consulting fees from Gilead, Merck, and ViiV; C. S. has received honoraria for lectures (Gilead and Janssen Cilag), advisory boards or travel grants from Gilead, Janssen, and MSD; M. M. has received honoraria for lectures, advisory boards (Janssen, ViiV, MSD) or travel grants (Janssen and MSD) from ViiV, Janssen, and MSD; J. R. has received honoraria for lectures, advisory boards or travel grants from Abivax, Boehringer (consulting fees), Galapagos, Gilead (honoraria and travel grant), Janssen (honoriaria), Merck (honoraria) Theratechnologies and ViiV (honoraria), and reports a role as GB member of EACS and Co-chair of EuroTEST; C. K. has received honoraria for lectures, advisory boards or travel grants and her institution has received research grants from Gilead (consulting), MSD (consulting, honoraria) and ViiV (consulting, honoraria); G. M. N. B. has received honoraria for lectures, advisory boards or travel grants and his institution has received research grants from Gilead (consulting fees, travel grants, and honoraria), Janssen, MSD (grants, consulting fees, travel grants, honoraria), and ViiV (consulting fees, travel grants, and honoraria), and Theratechnologies (consulting fees and honoraria); G. M. has received honoraria for lectures, advisory boards or travel grants and his institution has received research grants from Gilead, MSD, Theratechnologies, and ViiV; J. F. has received honoraria for lectures, advisory boards or travel grants and consulting fees from Gilead, Janssen, MSD, and ViiV; H. J. S. has received honoraria for lectures (Gilead, ViiV, MSD), advisory boards (Gilead, ViiV, MSD) or travel grants (Gilead) and his institution has received research grants (Gilead, ViiV, MSD, Janssen, GSK, Heidelberg) from Gilead, GSK, Heildelberg Immunotherapeutics, Janssen, MSD, and ViiV, and reports consulting fees from Gilead, ViiV, Janssen & Cilag, and MSD; payment for expert testimony from Gilead; receipt of equipment from Gilead; G. G. has received honoraria for lectures, advisory boards or travel grants and his institution has received research grants from Gilead, MSD, and ViiV; E. F. has received honoraria for lectures (Gilead and ViiV), advisory boards or travel grants from Gilead, Janssen, MSD, and ViiV; S. F. has received honoraria for lectures, advisory boards or travel grants and grants or contracts paid to institution from Gilead, MSD, ViiV, and Janssen; J. M. G. is a full-time employee of and owns stock in ViiV as Senior Global Medical Director since 1 May 2018; A. P. has received honoraria for lectures or advisory boards and consulting fees and his institution has received research grants from Gilead, Janssen, MSD, and ViiV; E. M. has received honoraria for lectures (Gilead, ViiV, MSD) or advisory boards and his institution has received research grants (MSD, ViiV) and consulting fees from Gilead, Janssen, MSD, Theratechnologies, and ViiV. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
(© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Methods: Primary endpoint was incident hypertension at 48 weeks. Secondary endpoints were changes in systolic (SBP) and diastolic (DBP) blood pressure; adverse events and discontinuations associated with high blood pressure; and factors associated with incident hypertension.
Results: At baseline, 191 (46.4%) participants had hypertension and 24 persons without hypertension were receiving antihypertensive medications for other reasons. In the 197 PWH (n = 98, DTG-I arm; n = 99, DTG-D arm) without hypertension or antihypertensive agents at baseline, incidence rates per 100 person-years were 40.3 and 36.3 (DTG-I) and 34.7 and 52.0 (DTG-D) at 48 (P = .5755) and 96 (P = .2347) weeks. SBP or DBP changes did not differed between arms. DBP (mean, 95% confidence interval) significantly increased in both DTG-I (+2.78 mmHg [1.07-4.50], P = .0016) and DTG-D (+2.29 mmHg [0.35-4.23], P = .0211) arms in the first 48 weeks of exposure to dolutegravir. Four (3 under dolutegravir, 1 under protease inhibitors) participants discontinued study drugs due to adverse events associated with high blood pressure. Classical factors, but not treatment arm, were independently associated with incident hypertension.
Conclusions: PWH at high risk for cardiovascular disease showed high rates of hypertension at baseline and after 96 weeks. Switching to dolutegravir did not negatively impact on the incidence of hypertension or blood pressure changes relative to continuing protease inhibitors.
Competing Interests: Potential conflicts of interest. A. G.-C. has received honoraria for lectures (Gilead, Janssen, Merck, Sharp & Dohme [MSD], and ViiV), advisory boards (ViiV) or travel grants (Gilead, MSD, and ViiV) and her institution has received research grants from Gilead, Janssen, MSD, and ViiV; L. W. has received honoraria for lectures and consulting fees (Gilead, MSD, ViiV), advisory boards or travel grants from Gilead, Janssen, MSD, and ViiV; S. R. has received honoraria for lectures, advisory boards or travel grants from Gilead, Janssen, and ViiV. He also reports payment or honoraria from MSD and Theratechnologies; P. D. has received honoraria for lectures or advisory boards and his institution has received research grants from Gilead, Janssen, MSD and ViiV. He also reports consulting fees and payment or honoraria from Gilead Sicences, ViiV Healthcare, Jansen & Cilag, Merck, Sharp & Dohme, Roche, GSK; M. G. has received honoraria for lectures, advisory boards or travel grants from Gilead, MSD, and ViiV; F. R. has received honoraria for lectures (Gilead, Merck, and ViiV), advisory boards (Merck and ViiV) or travel grants (Gilead and ViiV) from Gilead, Janssen, MSD, Theratechnologies, and ViiV. He also reports consulting fees from Gilead, Merck, and ViiV; C. S. has received honoraria for lectures (Gilead and Janssen Cilag), advisory boards or travel grants from Gilead, Janssen, and MSD; M. M. has received honoraria for lectures, advisory boards (Janssen, ViiV, MSD) or travel grants (Janssen and MSD) from ViiV, Janssen, and MSD; J. R. has received honoraria for lectures, advisory boards or travel grants from Abivax, Boehringer (consulting fees), Galapagos, Gilead (honoraria and travel grant), Janssen (honoriaria), Merck (honoraria) Theratechnologies and ViiV (honoraria), and reports a role as GB member of EACS and Co-chair of EuroTEST; C. K. has received honoraria for lectures, advisory boards or travel grants and her institution has received research grants from Gilead (consulting), MSD (consulting, honoraria) and ViiV (consulting, honoraria); G. M. N. B. has received honoraria for lectures, advisory boards or travel grants and his institution has received research grants from Gilead (consulting fees, travel grants, and honoraria), Janssen, MSD (grants, consulting fees, travel grants, honoraria), and ViiV (consulting fees, travel grants, and honoraria), and Theratechnologies (consulting fees and honoraria); G. M. has received honoraria for lectures, advisory boards or travel grants and his institution has received research grants from Gilead, MSD, Theratechnologies, and ViiV; J. F. has received honoraria for lectures, advisory boards or travel grants and consulting fees from Gilead, Janssen, MSD, and ViiV; H. J. S. has received honoraria for lectures (Gilead, ViiV, MSD), advisory boards (Gilead, ViiV, MSD) or travel grants (Gilead) and his institution has received research grants (Gilead, ViiV, MSD, Janssen, GSK, Heidelberg) from Gilead, GSK, Heildelberg Immunotherapeutics, Janssen, MSD, and ViiV, and reports consulting fees from Gilead, ViiV, Janssen & Cilag, and MSD; payment for expert testimony from Gilead; receipt of equipment from Gilead; G. G. has received honoraria for lectures, advisory boards or travel grants and his institution has received research grants from Gilead, MSD, and ViiV; E. F. has received honoraria for lectures (Gilead and ViiV), advisory boards or travel grants from Gilead, Janssen, MSD, and ViiV; S. F. has received honoraria for lectures, advisory boards or travel grants and grants or contracts paid to institution from Gilead, MSD, ViiV, and Janssen; J. M. G. is a full-time employee of and owns stock in ViiV as Senior Global Medical Director since 1 May 2018; A. P. has received honoraria for lectures or advisory boards and consulting fees and his institution has received research grants from Gilead, Janssen, MSD, and ViiV; E. M. has received honoraria for lectures (Gilead, ViiV, MSD) or advisory boards and his institution has received research grants (MSD, ViiV) and consulting fees from Gilead, Janssen, MSD, Theratechnologies, and ViiV. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
(© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)