Dolutegravir with enteral feeds in intensive care: nutrition vs viral suppression
Authors: Leung S , Al-Shakarchi Y , Shah S , Naous N , Boffito M , Bracchi M 
Published: November 2024

Abstract

Introduction
People living with HIV requiring admission to intensive care often receive enteral nutrition via feeding tubes. Enteral feeds contain cations which may interfere with dolutegravir (DTG) absorption due to chelation1. For this reason, temporal spacing (six hours before/ two hours after DTG administration2) is recommended, possibly leading to suboptimal caloric intake3. The clinical significance of the interaction between enteral feeds and DTG when co-administered is not fully understood and public data are sparse.

Aim
We aim to evaluate the impact and outcomes of co-administering DTG and enteral feeds.

Methods
Review of prospectively collected data on therapeutic drug monitoring (TDM) and electronic patient records of patients on DTG and enteral feeds, whilst in intensive care unit (ITU) between 2022 and 2023. Maximum (Cmax) and trough (Ctrough) DTG concentrations were measured and compared to reference ranges (DTG 50 mg once daily: Cmax 3340 ng/mL; Ctrough 830 ng/mL). All data were anonymised and collected as part of routine care for analysis. According to the National Research Ethics Service guidelines, further patient consent and ethical approval were not required.

Results
Six cases were identified with eight incidences of TDM sampling: 2 (33%) female; median age 34 (IQR 33-42); 3 (50%) non-white ethnicity; mean number of days on ITU 46 days; mean number of days into feeds 28 days; all (100%) suffered from hypoalbuminaemia (18-26 g/L). All patients were taking tenofovir-based regimens as their backbone antiretroviral therapy and once daily DTG, unless when co-administered with rifampicin where twice daily DTG is required to overcome enzyme induction effects of rifampicin. In three of the eight samples, temporal spacing with enteral feeds occurred as per SPC guidance2. The highest Cmax with once daily DTG seen in this cohort was 2201 ng/mL which was achieved without temporal spacing, whilst the lowest Ctrough (44 ng/mL) was observed in a different individual with sufficient temporal spacing. The viral loads measured while patients were receiving feeds varied, with 3 (50%) remaining suppressed. All (100%) patients had a fully suppressed viral load after enteral feeds ceased, including one patient who was naïve to treatment prior to admission with a high viral load.

Discussion/Conclusion
DTG Cmax were lower than those observed in literature regardless of temporal spacing from enteral feeds. Ctrough concentrations were also lower than expected in all cases. Six of eight Ctrough were lower than the DTG minimum effective concentration (MEC) of 300 ng/mL, however, only one was below IC90 for wildtype virus (64 ng/mL). Virological failure or onset of resistance was not observed in any of the patients. Multiple factors are likely to be contributing to low DTG concentrations, of which the most significant is likely impaired drug absorption, whilst nutritional feed co-administration seems to not be relevant.

References
1. Song, I, Pharmacokinetics of dolutegravir when administered with mineral supplements in healthy adult subjects. J Clin Pharmacol, 2015, 55(5), 490-496.
2. ViiV Healthcare UK Ltd, Summary of Product Characteristics (SmPC): Tivicay 50 mg Film-Coated Tablets, Last updated 04 Dec 2023. Available from: Tivicay 50 mg Film-Coated Tablets - Patient Information Leaflet (PIL) - (emc) (medicines.org.uk) [Accessed Apr 24].
3. Peev, MP, Causes and consequences of interrupted enteral nutrition: a prospective observational study in critically ill surgical patients, JPEN J Parenter Enteral Nutr, 2015, 39(1), 21-27.