Twice-Daily Dosing of Dolutegravir in Infants on Rifampicin Treatment: A Pharmacokinetic Substudy of the EMPIRICAL Trial

Background: We evaluated dolutegravir pharmacokinetics in infants with human immunodeficiency virus (HIV) receiving dolutegravir twice daily (BID) with rifampicin-based tuberculosis (TB) treatment compared with once daily (OD) without rifampicin. Methods: Infants living with HIV aged 1–12 months, we...

Descripción completa

Detalles Bibliográficos
Autores: Jacobs, Tom G., Mumbiro, Vivian, Cassia, Uneisse, Zimba, Kevin, Nalwanga, Damalie, Ballesteros, Álvaro, Domínguez Rodríguez, Sara, Tagarro García, Alfredo, Madrid, Lola, EMPIRICAL Clinical Trial Group, Et al.
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Europea (UEM)
Repositorio:ABACUS. Repositorio de Producción Científica
Idioma:español
OAI Identifier:oai:abacus.universidadeuropea.com:11268/12656
Acceso en línea:http://hdl.handle.net/11268/12656
Access Level:acceso abierto
Palabra clave:Rifampin
Pediatría
Enfermedad transmisible
Investigación médica
Goal 3: Ensure healthy lives and promote well-being for all at all ages
id ES_72eb07f5faa1ff4a15e76642aa70a92d
oai_identifier_str oai:abacus.universidadeuropea.com:11268/12656
network_acronym_str ES
network_name_str España
repository_id_str
spelling Twice-Daily Dosing of Dolutegravir in Infants on Rifampicin Treatment: A Pharmacokinetic Substudy of the EMPIRICAL TrialJacobs, Tom G.Mumbiro, VivianCassia, UneisseZimba, KevinNalwanga, DamalieBallesteros, ÁlvaroDomínguez Rodríguez, SaraTagarro García, AlfredoMadrid, LolaEMPIRICAL Clinical Trial GroupEt al.RifampinPediatríaEnfermedad transmisibleInvestigación médicaGoal 3: Ensure healthy lives and promote well-being for all at all agesBackground: We evaluated dolutegravir pharmacokinetics in infants with human immunodeficiency virus (HIV) receiving dolutegravir twice daily (BID) with rifampicin-based tuberculosis (TB) treatment compared with once daily (OD) without rifampicin. Methods: Infants living with HIV aged 1–12 months, weighing ≥3 kg, and receiving dolutegravir BID with rifampicin or OD without rifampicin were eligible. Six blood samples were taken over 12 (BID) or 24 hours (OD). Dolutegravir pharmacokinetic parameters, HIV viral load (VL) data, and adverse events (AEs) were reported. Results Twenty-seven of 30 enrolled infants had evaluable pharmacokinetic curves. The median (interquartile range) age was 7.1 months (6.1–9.9), weight was 6.3 kg (5.6–7.2), 21 (78%) received rifampicin, and 11 (41%) were female. Geometric mean ratios comparing dolutegravir BID with rifampicin versus OD without rifampicin were area under curve (AUC)0–24h 0.91 (95% confidence interval, .59–1.42), Ctrough 0.95 (0.57–1.59), Cmax 0.87 (0.57–1.33). One infant (5%) receiving rifampicin versus none without rifampicin had dolutegravir Ctrough <0.32 mg/L, and none had Ctrough <0.064 mg/L. The dolutegravir metabolic ratio (dolutegravir-glucuronide AUC/dolutegravir AUC) was 2.3-fold higher in combination with rifampicin versus without rifampicin. Five of 82 reported AEs were possibly related to rifampicin or dolutegravir and resolved without treatment discontinuation. Upon TB treatment completion, HIV viral load was <1000 copies/mL in 76% and 100% of infants and undetectable in 35% and 20% of infants with and without rifampicin, respectively. Conclusions: Dolutegravir BID in infants receiving rifampicin resulted in adequate dolutegravir exposure, supporting this treatment approach for infants with HIV–TB coinfection.20242024-02-0420242024-01-0120242024-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/11268/12656reponame:ABACUS. Repositorio de Producción Científicainstname:Universidad Europea (UEM)Españolspaopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:abacus.universidadeuropea.com:11268/126562026-06-11T12:41:27Z
dc.title.none.fl_str_mv Twice-Daily Dosing of Dolutegravir in Infants on Rifampicin Treatment: A Pharmacokinetic Substudy of the EMPIRICAL Trial
title Twice-Daily Dosing of Dolutegravir in Infants on Rifampicin Treatment: A Pharmacokinetic Substudy of the EMPIRICAL Trial
spellingShingle Twice-Daily Dosing of Dolutegravir in Infants on Rifampicin Treatment: A Pharmacokinetic Substudy of the EMPIRICAL Trial
Jacobs, Tom G.
Rifampin
Pediatría
Enfermedad transmisible
Investigación médica
Goal 3: Ensure healthy lives and promote well-being for all at all ages
title_short Twice-Daily Dosing of Dolutegravir in Infants on Rifampicin Treatment: A Pharmacokinetic Substudy of the EMPIRICAL Trial
title_full Twice-Daily Dosing of Dolutegravir in Infants on Rifampicin Treatment: A Pharmacokinetic Substudy of the EMPIRICAL Trial
title_fullStr Twice-Daily Dosing of Dolutegravir in Infants on Rifampicin Treatment: A Pharmacokinetic Substudy of the EMPIRICAL Trial
title_full_unstemmed Twice-Daily Dosing of Dolutegravir in Infants on Rifampicin Treatment: A Pharmacokinetic Substudy of the EMPIRICAL Trial
title_sort Twice-Daily Dosing of Dolutegravir in Infants on Rifampicin Treatment: A Pharmacokinetic Substudy of the EMPIRICAL Trial
dc.creator.none.fl_str_mv Jacobs, Tom G.
Mumbiro, Vivian
Cassia, Uneisse
Zimba, Kevin
Nalwanga, Damalie
Ballesteros, Álvaro
Domínguez Rodríguez, Sara
Tagarro García, Alfredo
Madrid, Lola
EMPIRICAL Clinical Trial Group
Et al.
author Jacobs, Tom G.
author_facet Jacobs, Tom G.
Mumbiro, Vivian
Cassia, Uneisse
Zimba, Kevin
Nalwanga, Damalie
Ballesteros, Álvaro
Domínguez Rodríguez, Sara
Tagarro García, Alfredo
Madrid, Lola
EMPIRICAL Clinical Trial Group
Et al.
author_role author
author2 Mumbiro, Vivian
Cassia, Uneisse
Zimba, Kevin
Nalwanga, Damalie
Ballesteros, Álvaro
Domínguez Rodríguez, Sara
Tagarro García, Alfredo
Madrid, Lola
EMPIRICAL Clinical Trial Group
Et al.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Rifampin
Pediatría
Enfermedad transmisible
Investigación médica
Goal 3: Ensure healthy lives and promote well-being for all at all ages
topic Rifampin
Pediatría
Enfermedad transmisible
Investigación médica
Goal 3: Ensure healthy lives and promote well-being for all at all ages
description Background: We evaluated dolutegravir pharmacokinetics in infants with human immunodeficiency virus (HIV) receiving dolutegravir twice daily (BID) with rifampicin-based tuberculosis (TB) treatment compared with once daily (OD) without rifampicin. Methods: Infants living with HIV aged 1–12 months, weighing ≥3 kg, and receiving dolutegravir BID with rifampicin or OD without rifampicin were eligible. Six blood samples were taken over 12 (BID) or 24 hours (OD). Dolutegravir pharmacokinetic parameters, HIV viral load (VL) data, and adverse events (AEs) were reported. Results Twenty-seven of 30 enrolled infants had evaluable pharmacokinetic curves. The median (interquartile range) age was 7.1 months (6.1–9.9), weight was 6.3 kg (5.6–7.2), 21 (78%) received rifampicin, and 11 (41%) were female. Geometric mean ratios comparing dolutegravir BID with rifampicin versus OD without rifampicin were area under curve (AUC)0–24h 0.91 (95% confidence interval, .59–1.42), Ctrough 0.95 (0.57–1.59), Cmax 0.87 (0.57–1.33). One infant (5%) receiving rifampicin versus none without rifampicin had dolutegravir Ctrough <0.32 mg/L, and none had Ctrough <0.064 mg/L. The dolutegravir metabolic ratio (dolutegravir-glucuronide AUC/dolutegravir AUC) was 2.3-fold higher in combination with rifampicin versus without rifampicin. Five of 82 reported AEs were possibly related to rifampicin or dolutegravir and resolved without treatment discontinuation. Upon TB treatment completion, HIV viral load was <1000 copies/mL in 76% and 100% of infants and undetectable in 35% and 20% of infants with and without rifampicin, respectively. Conclusions: Dolutegravir BID in infants receiving rifampicin resulted in adequate dolutegravir exposure, supporting this treatment approach for infants with HIV–TB coinfection.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-02-04
2024
2024-01-01
2024
2024-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/11268/12656
url http://hdl.handle.net/11268/12656
dc.language.none.fl_str_mv Español
spa
language_invalid_str_mv Español
language spa
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:ABACUS. Repositorio de Producción Científica
instname:Universidad Europea (UEM)
instname_str Universidad Europea (UEM)
reponame_str ABACUS. Repositorio de Producción Científica
collection ABACUS. Repositorio de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869410771042041856
score 15,301603

Similares en LA Referencia