The impact of integrase inhibitors on weight and metabolic profile in patients infected with HIV naïve to antiretroviral therapy

Abstract

Background Weight gain and metabolic diseases are common among persons with human immunodeficiency virus (HIV) infection after the initiation of antiretroviral therapy (ART). Since Integrase Strand Transfer Inhibitors (INSTIs) are included in first-line treatment, it is important to determine their impact on the onset of obesity and metabolic diseases in these patients. This study aimed to evaluate the effect of INSTIs on blood glucose, blood pressure (BP), dyslipidemia, and weight variation. Methods We performed a monocentric, retrospective cohort study in ART-naïve persons with HIV who initiated INSTI-based regimens between January 2015 and December 2022 and maintained them for at least 12 months. Data was collected at baseline, 6, 12, 24, 36, and 60 months after initiation. Laboratory characteristics, weight, and BP were compared between baseline and every visit during follow-up. Paired sample t-tests were performed to analyse the associations between analytical data at baseline and during follow-up and Fisher's Exact Tests were performed to analyse the differences in the categorical data (metabolic phenotypes). Results 349 patients were included in our study. 10,3% were female and the median age was 44 years. 92.8% were metabolically unhealthy at baseline. We observed a significant increase in BMI, weight, total cholesterol, and HDL mean values at every moment of follow-up with INSTI-based regimens. No statistically significant differences were observed in triglyceride levels during follow-up. The remaining parameters evaluated (systolic and diastolic BP, LDL cholesterol and fasting glucose levels) showed a significant increase in at least three different moments of follow-up. There was a gradual reduction in the number of patients with metabolically unhealthy non-obesity (MUN), with a simultaneous increase in the proportion of patients with metabolically unhealthy obesity (MUO). The patients under a dolutegravir-based regimen showed a significant increase in weight, BMI, systolic and diastolic BP, total cholesterol, and HDL cholesterol levels at 1 year of follow-up. Conclusion When started in individuals who are metabolically unhealthy at baseline, INSTIs appear to have a significant adverse impact on metabolic parameters, namely weight, blood glucose, BP and LDL levels. Dolutegravir was the INSTI that showed a more significant impact on weight and metabolic profile.