Twice-Daily Dosing of Dolutegravir in Infants on Rifampicin Treatment : A Pharmacokinetic Substudy of the EMPIRICAL Trial
© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America..
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 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:78 |
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| Enthalten in: |
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America - 78(2024), 3 vom: 20. März, Seite 702-710 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jacobs, Tom G [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.03.2024 Date Revised 02.04.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/cid/ciad656 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Twice-Daily Dosing of Dolutegravir in Infants on Rifampicin Treatment |b A Pharmacokinetic Substudy of the EMPIRICAL Trial |
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| 500 | |a Date Revised 02.04.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. | ||
| 520 | |a 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 | ||
| 520 | |a METHODS: Infants 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 | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSIONS: Dolutegravir BID in infants receiving rifampicin resulted in adequate dolutegravir exposure, supporting this treatment approach for infants with HIV-TB coinfection | ||
| 650 | 4 | |a Clinical Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a HIV | |
| 650 | 4 | |a dolutegravir | |
| 650 | 4 | |a drug–drug interaction | |
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| 650 | 4 | |a rifampicin | |
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