Bictegravir and Metformin Drug-Drug Interaction in People with Human Immunodeficiency Virus (HIV).

A drug-drug interaction (DDI) exists between bictegravir and metformin. Bictegravir inhibits renal organic cation transporter-2, leading to increased metformin plasma concentrations. The objective of this analysis was to evaluate the clinical implications of concomitant bictegravir and metformin administration. This was a retrospective, single-center, descriptive analysis evaluating people with human immunodeficiency virus (PWH) concurrently prescribed bictegravir and metformin between February 2018-June 2020. PWH lost to follow-up or non-adherent were excluded. Data collection included: hemoglobin A1C (HgbA1C), HIV RNA viral load, CD4 cell count, serum creatinine, and lactate. Adverse drug reactions (ADRs) were assessed by provider-documented, patient-reported symptoms of gastrointestinal (GI) intolerance and hypoglycemia. Metformin dose adjustments and discontinuations were recorded. Fifty-three PWH were included (116 screened; 63 excluded). GI intolerance was reported in three PWH (5.7%). There were no documented episodes of hypoglycemia or lactic acidosis. Five PWH had metformin dose reductions (N = 3 for unspecified reasons; N = 1 for GI intolerance) or discontinuation (N = 1 unrelated to ADRs). Both diabetes and HIV control improved (HgbA1C decreased by 0.7% with virologic control in 95% of PWH). Minimal ADRs were reported in PWH receiving concurrent metformin and bictegravir. Prescribers should be aware of this potential interaction; however, no empiric metformin total daily dose adjustment appears necessary.

Successful use of once-daily high-dose darunavir and dolutegravir in multidrug-resistant HIV.

WHAT IS KNOWN AND OBJECTIVE?: Antiretroviral (ARV) resistance may result during periods of consistently poor adherence. We report the successful use of a novel once-daily (QD) ARV regimen in a patient with multidrug-resistant (MDR) HIV. CASE SUMMARY: Once-daily darunavir 1200 mg/ritonavir 100 mg, dolutegravir and emtricitabine/tenofovir alafenamide was initiated with directly observed therapy. With the assistance of therapeutic drug monitoring, dolutegravir dosing was increased to 150 mg daily. The patient maintained virologic suppression for 18 months. WHAT IS NEW AND CONCLUSIONS?: In this case, QD darunavir/ritonavir achieved similar trough concentrations to twice daily dosing with dolutegravir dose titration necessitated and resulted in HIV virologic control.

Evaluation of the concurrent use of dolutegravir and metformin in human immunodeficiency virus-infected patients.

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.