Brief Report: Suboptimal Lopinavir Exposure in Infants on Rifampicin Treatment Receiving Double-dosed or Semisuperboosted Lopinavir/Ritonavir: Time for a Change.
Journal
Journal of acquired immune deficiency syndromes (1999)
ISSN: 1944-7884
Titre abrégé: J Acquir Immune Defic Syndr
Pays: United States
ID NLM: 100892005
Informations de publication
Date de publication:
01 05 2023
01 05 2023
Historique:
received:
10
11
2022
accepted:
17
01
2023
medline:
7
4
2023
pubmed:
2
2
2023
entrez:
1
2
2023
Statut:
ppublish
Résumé
Although super-boosted lopinavir/ritonavir (LPV/r; ratio 4:4 instead of 4:1) is recommended for infants living with HIV and receiving concomitant rifampicin, in clinical practice, many different LPV/r dosing strategies are applied due to poor availability of pediatric separate ritonavir formulations needed to superboost. We evaluated LPV pharmacokinetics in infants with HIV receiving LPV/r dosed according to local guidelines in various sub-Saharan African countries with or without rifampicin-based tuberculosis (TB) treatment. This was a 2-arm pharmacokinetic substudy nested within the EMPIRICAL trial (#NCT03915366). Infants aged 1-12 months recruited into the main study were administered LPV/r according to local guidelines and drug availability either with or without rifampicin-based TB treatment; during rifampicin cotreatment, they received double-dosed (ratio 8:2) or semisuperboosted LPV/r (adding a ritonavir 100 mg crushed tablet to the evening LPV/r dose). Six blood samples were taken over 12 hours after intake of LPV/r. In total, 14/16 included infants had evaluable pharmacokinetic curves; 9/14 had rifampicin cotreatment (5 received double-dosed and 4 semisuperboosted LPV/r). The median (IQR) age was 6.4 months (5.4-9.8), weight 6.0 kg (5.2-6.8), and 10/14 were male. Of those receiving rifampicin, 6/9 infants (67%) had LPV Ctrough <1.0 mg/L compared with 1/5 (20%) in the control arm. LPV apparent oral clearance was 3.3-fold higher for infants receiving rifampicin. Double-dosed or semisuperboosted LPV/r for infants aged 1-12 months receiving rifampicin resulted in substantial proportions of subtherapeutic LPV levels. There is an urgent need for data on alternative antiretroviral regimens in infants with HIV/TB coinfection, including twice-daily dolutegravir.
Sections du résumé
BACKGROUND
Although super-boosted lopinavir/ritonavir (LPV/r; ratio 4:4 instead of 4:1) is recommended for infants living with HIV and receiving concomitant rifampicin, in clinical practice, many different LPV/r dosing strategies are applied due to poor availability of pediatric separate ritonavir formulations needed to superboost. We evaluated LPV pharmacokinetics in infants with HIV receiving LPV/r dosed according to local guidelines in various sub-Saharan African countries with or without rifampicin-based tuberculosis (TB) treatment.
METHODS
This was a 2-arm pharmacokinetic substudy nested within the EMPIRICAL trial (#NCT03915366). Infants aged 1-12 months recruited into the main study were administered LPV/r according to local guidelines and drug availability either with or without rifampicin-based TB treatment; during rifampicin cotreatment, they received double-dosed (ratio 8:2) or semisuperboosted LPV/r (adding a ritonavir 100 mg crushed tablet to the evening LPV/r dose). Six blood samples were taken over 12 hours after intake of LPV/r.
RESULTS
In total, 14/16 included infants had evaluable pharmacokinetic curves; 9/14 had rifampicin cotreatment (5 received double-dosed and 4 semisuperboosted LPV/r). The median (IQR) age was 6.4 months (5.4-9.8), weight 6.0 kg (5.2-6.8), and 10/14 were male. Of those receiving rifampicin, 6/9 infants (67%) had LPV Ctrough <1.0 mg/L compared with 1/5 (20%) in the control arm. LPV apparent oral clearance was 3.3-fold higher for infants receiving rifampicin.
CONCLUSION
Double-dosed or semisuperboosted LPV/r for infants aged 1-12 months receiving rifampicin resulted in substantial proportions of subtherapeutic LPV levels. There is an urgent need for data on alternative antiretroviral regimens in infants with HIV/TB coinfection, including twice-daily dolutegravir.
Identifiants
pubmed: 36724434
doi: 10.1097/QAI.0000000000003168
pii: 00126334-202305010-00006
pmc: PMC10069754
doi:
Substances chimiques
Lopinavir
2494G1JF75
Ritonavir
O3J8G9O825
Rifampin
VJT6J7R4TR
Anti-HIV Agents
0
HIV Protease Inhibitors
0
Banques de données
ClinicalTrials.gov
['NCT03915366']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
42-46Investigateurs
Chishala Chabala
(C)
Kevin Zimba
(K)
Natasha Namuziya
(N)
Bwendo Nduna
(B)
Muleya Inambao
(M)
Jahit Sacarlal
(J)
W Chris Buck
(WC)
Uneisse Cassia
(U)
Muhammad Sidat
(M)
Elias Manjate
(E)
Alfeu Passanduca
(A)
Sónia Martins
(S)
Stella Langa
(S)
Natália Nipaco
(N)
Cinta Moraleda
(C)
Lola Madrid
(L)
Álvaro Ballesteros
(Á)
Alfredo Tagarro
(A)
Sara Domínguez-Rodríguez
(S)
Lilit Manukyan
(L)
Pablo Rojo
(P)
Hilda Angela Mujuru
(HA)
Mutsa Bwakura-Dangarembizi
(M)
Kusum Nathoo
(K)
Vivian Mumbiro
(V)
Constantine Mutata
(C)
Moses Chitsamatanga
(M)
Goodfrey Musoro
(G)
Tom Jacobs
(T)
Angela Colbers
(A)
David Burger
(D)
Informations de copyright
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.
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