Virological impact of the programmatic dolutegravir transition at Mildmay Hospital Uganda: a before-and-after cohort study with subgroup and trajectory analysis, 2016-2023.

backgroundUganda began transitioning to Dolutegravir (DTG)-based antiretroviral therapy (ART) in 2018. However, patient-level longitudinal evidence quantifying the virological impact of this transition from Ugandan facilities is limited. We evaluated whether the programmatic transition to DTG improved viral load (VL) suppression at Mildmay Hospital Uganda and assessed whether benefits were uniform across age groups and sexes.

methodsWe conducted a retrospective cohort study using 114,406 VL measurements from 18,756 patients collected between 2016 and 2023. We defined VL suppression as ≤ 200 copies/mL in accordance with Uganda national ART guidelines. Regimen timelines reconstructed from 25,095 regimen-change events enabled time-varying classification of each VL test by the most recently recorded regimen before VL testing. The primary analysis compared VL suppression in a pre-switch window (3 to 18 months before the switch) with a 12-month post-switch window (9 to 15 months after) in 1,928 eligible paired patients using McNemar's test. Secondary analyses included an interrupted time series (ITS) of monthly suppression rates, subgroup heterogeneity testing, and virological trajectory classification by regimen group.

resultsOverall VL suppression was 91.6%, rising from 89.2% in 2016 to 94.5% in 2023. 2.7% of tests recorded low-level viraemia (201-999 copies/mL) and 5.7% were unsuppressed. Among eligible switchers, suppression improved from 87.2% before the switch to 94.0% at 12 months after the switch (absolute difference + 6.8% points; 95% Confidence Interval (CI): 5.2-8.5; McNemar χ² = 63.09; p < 0.001), sustained at 94.7% at 24 months (p < 0.001). The adjusted odds ratio (aOR) for DTG exposure was 1.79 (95% CI: 1.63-1.97) and increased to 2.44 (95% CI: 2.13-2.80) by 12-24 months post-switch. All age groups and both sexes showed statistically significant improvements after the switch. Paediatric patients had the largest absolute gain of 12.2% points compared with 4.9% points for adults though post-switch suppression (89.8%) remained below 95%. DTG-direct initiators had the highest consistently suppressed trajectory rate at 82.0%, compared with 64.5% among documented non-DTG-only patients. Among 3,002 switchers with sufficient longitudinal data, 12.9% transitioned from non-suppressed to consistently suppressed trajectories after the switch.

conclusionsThe programmatic non-DTG-to-DTG transition was associated with a statistically significant and clinically meaningful improvement in VL suppression sustained through 24 months. Despite these gains, the cohort did not reach the Joint United Nations Programme on HIV/AIDS (UNAIDS) 95% VL suppression target under Uganda's stricter ≤ 200 copies/mL definition. Moreover, paediatric and adolescent patients remain priority groups for targeted adherence support. CLINICAL TRIAL NUMBER: Not applicable.