Dolutegravir with enteral feeds in intensive care: Case series with therapeutic drug monitoring.

Abstract

People with HIV admitted to the intensive care unit (ITU) often receive enteral nutrition via feeding tubes. Enteral feeds containing cations may interfere with dolutegravir (DTG) absorption via chelation and thus temporal spacing is recommended. This can lead to suboptimal caloric intake. We reviewed similar cases at our institution, an electronic health record and data collection, including people with HIV hospitalized in ITU with enterally administered DTG and therapeutic drug monitoring (TDM). Six cases (four males, two females, median age 34 years, median ITU admission 44.5 days, median 42.5 days on enteral nutrition) were identified with eight data points of TDM sampling. In three of eight instances, appropriate temporal spacing with enteral feeds occurred. All DTG C_max (maximum concentrations) were lower than 3340-3670 ng/mL, regardless of temporal separation from enteral feeds. C_trough (trough plasma concentrations) were also lower than 830-1110 ng/mL with the exception of one case. Six of eight C_trough were lower than the DTG minimum effective concentration (MEC) of 300 ng/mL. However, only one was below PA-IC₉₀ (in vitro protein-adjusted 90% maximal inhibitory concentration) for wildtype virus (64 ng/mL). Multiple factors such as delayed gastric emptying and changes in gastric pH are likely contributing to impaired drug absorption and reduced DTG concentrations in critically ill patients. The data on nutritional feed co-administration demonstrate that therapeutic concentrations and virological responses can be achieved with frequent viral load (VL) monitoring and TDM. Further pharmacokinetic studies on DTG in critically ill patients are warranted to better understand the impact of this co-administration.