Target trial emulation in Johannesburg shows dolutegravir associated with greater weight and blood pressure increases versus efavirenz

OBJECTIVE: Using the Target Trial Emulation Framework, we evaluated the impact of initiating dolutegravir versus efavirenz on 12- and 24-month weight, body mass index (BMI), blood pressure (BP), and incident hypertension among treatment-naïve individuals in Johannesburg, South Africa from 2019 to 2022. METHODS: We used linear models to estimate the mean difference in weight, BMI, BP and a log-binomial model to estimate the causal risk difference of incident hypertension, adjusting for patient characteristics via inverse probability weighting. RESULTS: Among 2930 people initiating treatment from 2019 to 2022, 1847 initiated dolutegravir and 1083 initiated efavirenz. At 12-months, mean difference comparing dolutegravir to efavirenz in weight was 2.9 kg (95% Confidence Interval (CI): -0.3, 5.5), BMI was 0.8 kg/m (95% CI: -0.3, 1.9), diastolic BP was 1.6 mmHg (95% CI: -0.7, 3.9) and systolic BP was 3.9 mmHg (95% CI: 1.2, 6.6). Risk of incident hypertension rose by 35% (95% CI: 0.04, 0.5). At 24-months, mean weight difference was 1.9 kg (95% CI: -1.3, 5.1), BMI was 0.6 kg/m (95% CI: -0.6, 1.9), diastolic BP was -0.4 mmHg (95% CI: -1.8, 5.1) and systolic BP was 1.7 mmHg (95% CI: -1.8, 5.1). Risk of incident hypertension rose by 22% (95% CI: -0.1, 0.4). CONCLUSIONS: Dolutegravir was associated with greater increases in weight, systolic BP, and incident hypertension over 24-months, particularly in the first 12-months. Future research is needed to determine whether this reflects a direct effect of dolutegravir or the weight-suppressing effects of efavirenz.