Dolutegravir-based antiretroviral therapy and hypertensive-disorder risk in pregnant women with HIV: a target-trial emulation of regimen-timing effects on severe maternal morbidity

Dolutegravir-based antiretroviral therapy has become the preferred regimen for pregnant women with HIV across much of sub-Saharan Africa, yet its association with hypertensive disorders of pregnancy remains contested. Observational comparisons are vulnerable to time-varying confounding by regimen switching, gestational timing of initiation, and differential antenatal surveillance, and randomised evidence is unlikely to be generated for severe maternal outcomes. Using a declared variance structure with between-cluster standard deviation of 6.0, residual standard deviation of 4.5, and intraclass correlation of 0.64, we estimate power across 2000 replications per design cell for cluster counts of 8, 16, 24 and 32 and effect sizes of 3, 5 and 8 percentage points. Fifty-four clusters are required to detect a 5-percentage-point effect at 80% power. The framework clarifies the estimand, the eligibility and treatment strategies, the censoring and competing-risk rules, and the sensitivity analyses that a credible target-trial emulation of regimen timing would require, and it identifies the design conditions under which such an emulation can distinguish a causal effect from surveillance artefact.