Hyperglycemia After Dolutegravir-Based Antiretroviral Therapy

Abstract

Background Antiretroviral therapies prolong life expectancy and improve the quality of life of HIV-infected patients. Despite the documented benefits of antiretroviral drugs, its use is not without side effects. Here, we report cases of new onset diabetes mellitus after taking a dolutegravir (DTG)-based ART regimen. Case Presentation HIV-infected patients who had been on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART regimens for more than a decade were shifted to integrase strand transfer inhibitors (dolutegravir)-based ART regimen as recommended by the National Comprehensive HIV Care Guideline. They were diagnosed to have diabetes mellitus with or without diabetic ketoacidosis (DKA) as evidenced by polyuria, polydipsia and fatigue, severe hyperglycemia (plasma glucose level >250 mg/dl) with or without ketonuria (3+) after 1–12 months of DTG-based ART regimen. Two of the patients who presented with DKA were treated with intravenous fluids and regular insulin. NPH insulin was started following recovery from DKA, which later shifted to metformin. One of the patients who presented with severe hyperglycemia without DKA was started with NPH insulin, which later shifted to metformin. Good glycemic control was obtained with metformin, while the DTG-based ART regimen was continued. Conclusion Hyperglycemia is 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.

Comparison of Renal Function Biomarkers of Serum Creatinine and Cystatin C in HIV-Infected People on Dolutegravir-Containing Therapy

“…For instance, DTG may worsen diabetes management in HIV-infected patients because its chelating effect of mg 2+ may undermine insulin action. 33 , 34 Their kidney function should be monitored more closely and in combination with more renal biomarkers to decide on appropriate antiretroviral therapy.…”

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

“…ART = antiretroviral treatment; BMI = body mass index; DTG = Dolutegravir metabolism. [18][19][20][21]26,27 The mechanism by which DTG causes deranged glucose metabolism is not well understood, although it is hypothesized that DTG causes insulin resistance by chelating magnesium ions which are needed as cofactors for effective action of insulin. 28 Our findings indicate that PLHIV who had previously been prescribed DTG-based ART had seven times greater odds of having hyperglycemia compared to those who had been previously prescribed non-DTG ART regimens, even after controlling for potential confounders such as age, BMI, and hypertension as a co-morbidity.…”

“…16 Despite its benefits, emerging evidence from case reports, case series, and clinical trials have suggested an association between DTG and disorders of glucose metabolism such as hyperglycemia. [17][18][19][20] A more recent crosssectional study conducted in Zambia found that when compared to NNRTI's, DTG-based ART was associated with double the risk of developing metabolic syndrome among PLHIV; metabolic syndrome consists of hyperglycemia, hypertension, and dyslipidemia among other parameters all of which are known to increase the risk of DM. 21 In Uganda and throughout SSA, where DTG is being widely rolled out and there is an increasing burden of NCDs among PLHIV and the general population, there is a paucity of information on the association between use of DTGbased ART and hyperglycemia.…”

“…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.…”

Patient experiences of switching from Efavirenz- to Dolutegravir-based antiretroviral therapy: a qualitative study in Uganda

“…There is need for careful monitoring of DTG since side-effects not previously reported in early clinical trials, such as weight gain, have subsequently been reported from observational studies and randomised trials [ 29 – 31 ]. The programmatic roll-out of DTG-based first-line ART should prioritize effective diabetes prevention and treatment strategies for patients switched to DTG [ 32 ]. Our study suggests that giving short weekly return appointments to participants helps to monitor drug switching and manage possibly-related side effects.…”