Strong cytochrome P450 (CYP) 3A4 inhibitors may induce Cushing syndrome and subsequent adrenal insufficiency when administered concurrently with corticosteroids. This drug–drug interaction has been well described with HIV protease inhibitors. A similar drug–drug interaction with corticosteroids and other strong CYP 3A4 inhibitors (antifungals [imidazoles]) has recently been reported but remains less well known. To our knowledge, we report the first case of probable drug-induced Cushing syndrome with subsequent adrenal insufficiency as a result of concomitant oral voriconazole with intranasal mometasone and inhaled fluticasone administration as well as a review of the current literature supporting this drug–drug interaction.

The administration of antiretroviral therapy (ART) in intubated critically ill patients may be challenging. Limited pharmacokinetic data exist characterizing the effects of crushed ART with subsequent enteral administration on antiretroviral drug concentrations or the clinical impact on HIV virologic suppression. We report a case of a 27-year-old HIV-positive male with presumed multidrug-resistant HIV and a diagnosis of lymphoma who required enteral ART administration after intensive care unit admission. Crushed twice-daily dolutegravir (separated from enteral nutrition by 2 hours) and rilpivirine (concurrently with a bolus feed) were administered via an orogastric tube. Therapeutic drug monitoring for both dolutegravir and rilpivirine demonstrated antiretroviral absorption via the enteral route (both values slightly below the therapeutic laboratory reference range) with continued virologic suppression.

An analysis of the interaction between dolutegravir and metformin was conducted in the HIV ambulatory clinic setting. This was a multicenter, retrospective case series evaluating adult, HIV-infected patients concurrently prescribed dolutegravir and metformin. Historical electronic medical records were utilized to collect case-specific data. Laboratory parameters including serum creatinine (SCr), hemoglobin A1c (HgbA1c), plasma HIV RNA, CD4 cell count, and lactate were reviewed. Adverse drug reactions were assessed using patient-reported gastrointestinal intolerance and hypoglycemic symptoms. Metformin dose reduction or discontinuation was also recorded. Nineteen patients identified as concurrently taking metformin and dolutegravir were included. Eighteen patients were on metformin prior to dolutegravir initiation, with 13 having received metformin for at least six months prior to dolutegravir. At the time of dolutegravir initiation, one patient had a preemptive metformin dose reduction. Seven patients were initiated on dolutegravir with a metformin dose greater than 1000 mg daily. Eleven patients had baseline and three- to six-month follow-up HgbA1c. Of those 11 patients, eight had stable or decreased values. Thirteen of the 19 patients had an increase in SCr, with a median increase of 0.3 mg/dl (0.03–0.43). Gastrointestinal distress (N = 3) and hypoglycemic symptoms (N = 3) were reported in a total of five patients. Adverse drug reactions resulted in metformin dose reduction (N = 2) and/or discontinuation (N = 2). There were no reported cases of lactic acidosis. Providers concurrently prescribing dolutegravir and metformin should be aware of potential consequences with this combination and may consider an empiric metformin dose reduction to prevent intolerable adverse drug reactions.

Enteral antiretroviral (ARV) administration is necessary in human immunodeficiency virus (HIV)–positive patients with dysphagia or oral cancer or during an acute hospitalization with altered mental status.^1-3 Recommended ARV regimens for most patients with HIV infection include an integrase strand transfer inhibitor (INSTI) (bictegravir, dolutegravir, or raltegravir) in combination with 2 nucleoside/tide reverse transcriptase inhibitors (NRTIs).⁴ Both dolutegravir and raltegravir maintain virologic suppression when crushed and enterally administered via a feeding tube.^3,5 Bictegravir is only available as a fixed-dose combination (FDC) tablet with emtricitabine and tenofovir alafenamide. FDC emtricitabine and tenofovir alafenamide with dolutegravir have resulted in viral suppression...