Glucose metabolism changes in Ugandan HIV patients on dolutegravir
Project summary
There has been improved survival of HIV patients in sub-Saharan Africa where the HIV incidence and prevalence is notably high. This could be attributed to the scale up of ART programs and improved anti-retroviral therapy (ART) efficacy. With aging and cumulative side effects of ART, the burden of non-communicable diseases (NCDs) in people living with HIV (PLHIV) has been on the rise. Multiple countries moved to adopt integrase strand inhibitor (INSTI) based ART, particularly DTG containing regimens with the majority of low-middle income countries (LMIC) adopting DTG based ART as the preferred first line therapy. Despite the good side effect profile, DTG has been linked with incident accelerated hyperglycaemia and worsening hyperglycaemia in patients with diabetes. Large population cohort studies however have been contradictory on the association between INSTIs and hyperglycemia. In the proposed studies, we hope to pool data in a meta-analysis to determine if there is indeed an association between INSTI use with insulin resistance and incident diabetes. To further explore this association, a prospective cohort of 303 Ugandan HIV patients on dolutegravir, recruited between February – 2021 and September - 2021 is being followed up for 48 weeks with serial blood glucose and insulin kinetic measurements i.e., insulin secretion at fasting state, insulin secretion at non-fasting state, insulin sensitivity and insulin clearance. We plan to describe glucose metabolism changes in this cohort for 48 weeks. Additionally, we shall compare insulin kinetic trajectories in patients with incident hyperglycemia and those without as well as characterize changes in insulin kinetics after with-holding dolutegravir in patients with incident diabetes. We believe these data will inform surveillance and diabetes treatment strategies in this group of patients.