Blood glucose trajectories and incidence of diabetes mellitus in Ugandan people living with HIV initiated on dolutegravir

Abstract

Background Following reports of anti-retroviral therapy (ART) experienced Ugandan people living with HIV (PLHIV) presenting with diabetic ketoacidosis weeks to months following a switch to dolutegravir (DTG), the Uganda Ministry of Health recommended withholding DTG in both ART naïve and experienced PLHIV with diabetes mellitus (T2DM), as well as 3-monthly blood glucose monitoring for patients with T2DM risk factors. We sought to determine if the risk of T2DM is indeed heightened in nondiabetic ART naïve Ugandan PLHIV over the first 48 weeks on DTG. Methods Between January and October 2021, 243 PLHIV without T2DM were initiated on DTG based ART for 48 weeks. Two-hour oral glucose tolerance tests (2-h OGTT) were performed at baseline, 12, and 36 weeks; fasting blood glucose (FBG) was measured at 24 and 48 weeks. The primary outcome was the incidence of T2DM. Secondary outcomes included: incidence of pre-Diabetes Mellitus (pre-DM), median change in FBG from baseline to week 48 and 2-h blood glucose (2hBG) from baseline to week 36. Linear regression models were used to determine adjusted differences in FBG and 2hBG from baseline to weeks 48 and 36 respectively. Results The incidence of T2DM was 4 cases per 1000 PY (1/243) and pre-DM, 240 cases per 1000 person years (PY) (54/243). There was a significant increase in FBG from baseline to week 48 [median change from baseline (FBG): 3.6 mg/dl, interquartile range (IQR): − 3.6, 7.2, p-value (p) = 0.005] and significant reduction in 2hBG (2hBG: − 7.26 mg/dl, IQR: − 21.6, 14.4, p = 0.024) at week 36. A high CD4 count and increased waist circumference were associated with 2hBG increase at week 36. Conclusion We demonstrated a low incidence of T2DM in Ugandan ART-naïve patients receiving DTG. We also demonstrated that longitudinal changes in BG were independent of conventional risk factors of T2DM in the first 48 weeks of therapy. Restricting the use of dolutegravir in Ugandan ART naïve patients perceived to be high risk for diabetes mellitus may be unwarranted.

Dolutegravir-related hyperglycemia among children and adolescents <18 years in Northern and Eastern Uganda: A cross-sectional study

“…Additionally, Odenyo et al; found that overweight patients were 1.7 times more likely to develop hyperglycemia. In terms of BMI for age z scores, the current study’s findings align with studies by Namara et al; and the GLUMED study in Kampala, which also did not find a significant association between BMI and hyperglycemia (20,26). The duration on Dolutegravir also did not show a statistically significant association with hyperglycemia in contrast to the findings by Lamorde et al; in Uganda (5).…”

Should dolutegravir always be withheld in people with HIV on dolutegravir with incident diabetes mellitus? A case report

“…Over the same period, he experienced worsening insulin resistance and concurrent increase in pancreatic beta cell function which could have been compensatory. Much as the worsening insulin resistance could be attributed to the weight gain, on evaluation of glucose changes in the whole study cohort, there was signi cant improvement in blood glucose despite a signi cant increase in BMI over the 48 weeks of follow up [9]. This may suggest that this patient had an inherent risk of developing T2DM, independent of weight gain and exposure to DTG.…”

“…This 44-year-old man was enrolled in a prospective cohort study (GLucose Metabolism changes in Ugandan HIV patients on Dolutegravir, GLUMED study) evaluating glucose metabolism changes in antiretroviral therapy (ART) naïve Ugandan people with HIV (PWH) on tenofovir/ lamivudine/ dolutegravir (TDF/3TC/ DTG) for 48 weeks [9]. Patients underwent serial 2-hour oral glucose tolerance tests (OGTTs) at baseline, 12 and 36 weeks.…”

Dolutegravir use over 48 weeks is not associated with worsening insulin resistance and pancreatic beta cell function in a cohort of HIV-infected Ugandan adults

“…2) Most patients presenting with accelerated hyperglycemia are heavily ART experienced before switch to dolutegravir or other integrase inhibitors [11], [28]- [30], [32]. 3) In ART naïve Ugandan patients on dolutegravir, the incidence of diabetes mellitus is very low, comparable to safety data results in landmark DTG trials and largely less than in most cohort studies in Europe and North America [15]. 4)…”