Decreased Absorption of Dolutegravir and Tenofovir Disoproxil Fumarate, But Not Emtricitabine, in anHIV‐Infected Patient Following Oral and Jejunostomy‐Tube Administration

Abstract

The use of enteral feeding tubes to administer antiretroviral medication administration is necessary in certain patients with human immunodeficiency virus (HIV) infection. However, adequacy of drug exposures after these administration routes are largely unknown, making dosing recommendations and the attainment of viral suppression challenging in this patient population. This report describes a patient with advanced HIV infection and a complicated medical history, including long-term intractable nausea/vomiting necessitating antiretroviral medication administration via a Roux-en-Y jejunostomy (J)-tube. Pharmacokinetic assessments were performed to compare differences in antiretroviral drug absorption and plasma exposure following oral and J-tube administration of dolutegravir, tenofovir disoproxil fumarate, and emtricitabine. Results were also compared to published pharmacokinetic data in HIV-infected individuals. Exposure to dolutegravir and tenofovir were similar between J-tube and oral administration routes, whereas emtricitabine exposure was 38% lower when administered via J-tube. However, in comparison to reference data in HIV-infected individuals taking these medications orally, exposure to dolutegravir and tenofovir was 75%–76% and 55%–61% lower, respectively, following both routes of administration. Emtricitabine exposure was similar to and 71% higher than reference data following J-tube and oral administration, respectively. This report highlights the importance of performing pharmacokinetic assessments in patients with the potential for impaired drug absorption to ensure antiretroviral treatment success.

The Effect of Veno-Arterial Extracorporeal Oxygenation and Nasogastric Tube Administration on the Pharmacokinetic Profile of Abacavir, Lamivudine and Dolutegravir: A Case Report

“…The DTG C t of 820 ng/ml following the higher 50 mg twice daily dosing was similar to the reference of 830 ng/ml with 50 mg daily dosing. Another case report in a CI-PLWH found that DTG exposure was similar when administered oral versus jejunostomy tube, but the AUC exposure was 76% and 75% lower compared with the literature, respectively [17]. Similar to the current report, all previous reports describe maintenance of viral suppression with altered DTG administration [16–19].…”

“…Specifically, the DTG AUC 0–t and C max was 26% and 30% higher compared with references [15]. Few case reports assess crushed DTG in PLWH [16–19]. One case report described a CI-PLWH where DTG was increased to 50 mg twice daily given crushed via gastrostomy tube.…”

Sustained virologic suppression with abacavir, emtricitabine, and crushed dolutegravir and tenofovir alafenamide in a patient with HIV and eosinophilic esophagitis

“…Similarly, Brooks et al. 2 observed lower levels of DTG when administered once-daily via jejunostomy tube. Altered bioavailability with administration of crushed combination tablets containing either DTG or tenofovir alafenamide (TAF) has also been reported.…”

The management of treatment-experienced HIV patients (including virologic failure and switches)

“…The data in this area is limited but emerging. [61][62][63] Providers should consult with their clinical pharmacists and the manufacturer, or perform a literature search for the most recent data. The University of Toronto also maintains a summary of data on their website, which may be a useful resource (https://hivclinic.ca/).…”