345. Acute Onset Diabetic Ketoacidosis/Hyperosmolar Hyperglycemic State in Patients Taking Integrase Strand Transfer Inhibitors

Abstract

BackgroundA few case reports have noted uncontrolled hyperglycemia in patients switched to dolutegravir. Several cohort studies have found increased weight gain among patients treated with integrase inhibitors (INSTI). We present clinical observations among 3 patients admitted to hospital for diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) while receiving INSTIs for the management of HIV.MethodsCase 1: A 44-year-old man with HIV and dyslipidemia presented with altered mental status and lethargy. A fingerstick glucose was >600 mg/dL. Chemistries revealed glucose of 1,600 mg/dL and an elevated β-hydroxybutyrate. HbA1c was 12.4%. His antiretroviral regimen consisted of cEVG/TAF/FTC for the last 3 years. Previous HbA1c levels were 5.7% and 6.2% (Figure 1). Case 2: A 55-year-old woman with HIV, hypertension, dyslipidemia, and obesity presented with polyuria and polydipsia. The blood glucose level was >1,200 mg/dL with an anion gap >30 and HbA1c of 15%. Previous HbA1c levels ranged between 5.6 and 5.8% (Figure 2). She had been taking ABC/FTC/DTG for 2 years.Case 3: A 64 yo man with a history of HIV, hypertension, and obesity presented with polyuria and polydipsia. The blood glucose level was 1,152 mg/dL with no anion gap and HbA1c of 13.4%. Six months before, he had been switched from a c/DRV- based ART regimen to ABC/FTC/DTG. Previous HbA1c levels ranged between 5.8% and 6.2% (Figure 3).ResultsDiscussion: In the first 2 patients, the presentation with acute onset DKA occurred more than a year after being on an INSTI-based regimen; however, the latter patient presented with HHS within 6 months of being switched to an INSTI-containing regimen. The mechanism of action of INSTIs causing weight gain or an association with hyperglycemia is still under investigation.ConclusionAlthough the temporal onset of DKA and HHS while receiving INSTIs was not precise, the possible association of INSTIs and their direct effects on insulin resistance and diabetes warrant additional attention from post-market data. Meanwhile, providers should monitor INSTI-treated patients closely, especially those with features of metabolic syndrome. Disclosures All authors: No reported disclosures.

Bictegravir-Based Antiretroviral Therapy-Associated Accelerated Hyperglycemia and Diabetes Mellitus

“…Recent case reports have also documented the development of accelerated hyperglycemia and DKA after initiation of these therapies. In One case series, 3 patients developed DKA while on DTG- or elvitegravir-based regimens [ 12 ]. However, 2 of the 3 reported patients developed diabetes more than 1 year after starting an INSTI-based regimen, making the association with ART therapy less clear.…”

Hyperglycemia After Dolutegravir-Based Antiretroviral Therapy

“…7 Recently, there is mounting evidence that INSTIs cause deranged glucose metabolism. [8][9][10][11][12][13][14][15][16][17] Severe a potential and noticed side effect of the DTG-based ART regimen. Baseline and periodic monitoring of plasma glucose might be required in ART regimens containing dolutegravir.…”

“…Recently, there have been a few documented reports on deranged glucose metabolism with integrase strand transfer inhibitors (INSTIs) use. [8][9][10][11][12][13][14][15][16][17] SAILING, SPRING-2, SINGLE and VIKING-3 clinical trials reported the incidence of moderate (plasma glucose, 126-250 mg/dl) and severe hyperglycemia (plasma glucose, >250 mg/dl) were 6-9% and 1-2%, respectively, after INSTIs therapy. [8][9][10][11] This case series is the first of its kind in Ethiopia to report on new onset diabetes mellitus after dolutegravir-based ART use.…”

“…Horikawa et al and Lamonde et al[12][13][14][15] INSTIs are believed to work by chelating mg 2+ to prevent HIV from integrating into host DNA. Chelating mg 2+ by INSTIs may lead to disorders of glucose metabolism, because mg 2+ also serves as a cofactor in post-receptor insulin action [13][14][15][16][17]. Two of the patients who presented with DKA were treated with intravenous fluids and regular insulin.…”

The risk of hyperglycemia associated with use of dolutegravir among adults living with HIV in Kampala, Uganda: A case-control study

“…In multivariable analysis, patients with prior DTG use had seven times greater odds of subsequent diagnosis of hyperglycemia compared to those who had non-DTG-based regimens (adjusted odds ratio [aOR] 7.01, 95% CI 1.96-25.09). The odds of hyperglycemia also increased with age (56 years and above vs. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] aOR 12.38,) and hypertension (aOR 5.78,). Our study demonstrates a strong association between prior DTG exposure and subsequent diagnosis of hyperglycemia.…”