Evaluating the Glycemic Effects of Dolutegravir and Its Predictors Among People With Human Immunodeficiency Virus in Uganda: A Prospective Cohort Study

Abstract Background Dolutegravir (DTG), a key component of the recommended human immunodeficiency virus (HIV) treatment regimens in Uganda, has been associated with hyperglycemia. We evaluated its influence on hyperglycemia risk to create a hyperglycemia risk stratification tool for patient monitoring. Methods We conducted a prospective cohort study at 3 sites with 628 HIV-positive patients on tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD). Participants included both nucleoside reverse transcriptase inhibitor–experienced (exposed) and antiretroviral therapy (ART)–naive (nonexposed) groups. Follow-up occurred every 6 months with random blood sugar (RBS) testing every 3 months. Participants with RBS ≥7 mmol/L were classified as hyperglycemic and underwent glycated hemoglobin (HbA1c) testing, confirming diabetes with a 6.5% cut-off. Results The study found a hyperglycemia incidence rate of 24.5 (95% confidence interval [CI], 19.3–31.1) cases per 100 person-years (PY) and a diabetes incidence rate of 5.8 cases (95% CI, 3.6–9.3) per 100 PY. Hyperglycemia incidence was slightly lower in nonexposed (20.8 cases per 100 PY) versus exposed groups (25.2 cases per 100 PY). Multivariable analysis indicated a trend toward lower hyperglycemia risk (adjusted hazard ratio [aHR], 0.78 [95% CI, .37–1.66]; P = .52) and substantially lower diabetes incidence (aHR, 0.34 [95% CI, .04–2.82]; P = .32) in the nonexposed group. Significant factors for hyperglycemia included age (P < .001), study site (P < .001), and DTG-based ART duration (P = .02). Conclusions Our study showed an increased incidence of hyperglycemia with age, study site, and duration of DTG exposure in people with HIV on TLD. We suggest integrated screening and care for hyperglycemia and diabetes in HIV services, especially when initiating DTG regimens.