Prevalence and factors associated with Dolutegravir-related hyperglycemia among children and adolescents <18 years attending Soroti Regional Referral and Lira Regional Referral Hospitals

Abstract

Background: The World Health Organization (WHO) recommended Dolutegravir (DTG) as the preferred anchor drug in first and second line Anti-Retroviral Treatment (ART) regimens owing to its high genetic barrier to resistance, better tolerability and less drug interactions. A number of studies and case reports however have demonstrated new onset hyperglycemia among adults initiated or transitioned to DTG. There is paucity of data on DTG related hyperglycemia among children and adolescents and furthermore, glycemic screening is not routinely done for children and adolescents on a DTG based ART regimen. Objectives: To determine the prevalence and factors associated with DTG related hyperglycemia among children and adolescents <18 years attending Soroti and Lira Regional Referral Hospitals. Methodology: This cross-sectional study was conducted from November 2022 to June 2023 at Soroti and Lira Regional Referral Hospitals. A total of 240 children and adolescents under the age of 18, on a DTG based treatment regimen, were consecutively enrolled. Socio-demographic, anthropometric measurements, clinical, and laboratory variables were collected using a questionnaire and clinic abstraction form. Random blood glucose testing and urine dipstick analysis were performed, and samples collected for HbA1c analysis. Data were entered into epiData version 4.6, cleaned, and analyzed using STATA version 17.0. Simple logistic regression was used to identify factors independently associated with DTG-related hyperglycemia. A p-value < 0.05 was considered statistically significant in the multivariate analysis. Results: Of the 240 study participants, 133/240 (55.4%) were female and 172/240 (71.7%) were over 10 years. The prevalence of Dolutegravir-related hyperglycemia was 49/240 (20%) of which 47/49 (95.9%) met the criteria for prediabetes. Majority, 46/49 (93.8%) were diagnosed using HBA1C alone. Having health education talks on Adverse events related to DTG use (cOR 0.3, 95% CI, 0.1-0.6), P=0.001 was found to be protective against hyperglycemia. Adjusting for other factors at multivariate, having health education was associated with less odds of hyperglycemia (aOR 0.4, 95% CI 0.2-0.9), P = 0.035. Conclusion and Recommendations: This study revealed a prevalence of 20% for DTG-related hyperglycemia among children and adolescents. Health education talks on adverse events associated with Dolutegravir use were found to be protective against hyperglycemia. Routine glycemic monitoring should be implemented for children and adolescents on DTG at the initiation and throughout the treatment course through estimation of plasma glucose levels especially using glycated hemoglobin measurements. Additionally, health education talks focusing on how to mitigate the potential adverse effects of DTG should be emphasized to support lifestyle modifications that reduce the occurrence hyperglycemia. Key words: Hyperglycemia, Dolutegravir