Maternal antiretroviral therapy adherence and birth-outcome disparities in Malawi: a target-trial emulation of pharmacy-refill timing effects on reproductive health

Malawi's prevention-of-mother-to-child-transmission programme has achieved near-universal antiretroviral coverage, yet birth-outcome disparities persist among women living with HIV. Observational analyses of adherence and birth outcomes are vulnerable to time-varying confounding and immortal-time bias, because women who remain in care long enough to accumulate refills are systematically different from those who discontinue. The design is a before-after-control-impact (BACI) estimator with between-cluster SD 6.0, residual SD 4.5 and intraclass correlation 0.64, evaluated 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. Power was estimated across 2000 design cells. The analysis indicates that 54 clusters are required to detect a 5-percentage-point effect at 80% power under this variance structure, and that the minimum detectable effect falls steeply as cluster count rises from 8 to 32. The framework reframes refill timing as a sequence of sustained treatment strategies rather than a baseline exposure, and specifies the estimand, eligibility criteria, censoring rules and sensitivity analyses that a field implementation would require. The contribution is methodological: it clarifies what a defensible adherence–birth-outcome comparison must estimate, and it quantifies the design burden that such a comparison imposes in the Malawian antenatal setting.