Prevention of <scp>HBV</scp> Mother‐To‐Child Transmission ( <scp>MTCT</scp> ) Using Targeted <scp>HBV</scp> Birth Dose, and Treatment of High Viral Load Pregnant Women in Uganda

ABSTRACT Hepatitis B virus (HBV) mother‐to‐child transmission (MTCT) remains a major challenge in Uganda, where 43% of births occur at home, and access to timely birth dose (BD) vaccination is limited. We evaluated the impact of combining universal three‐dose (3D) infant vaccination, targeted BD vaccination, and maternal antiviral treatment for high viral load (HVL) mothers on HBV prevalence among infants. In a prospective 18‐month cohort study at five regional maternity hospitals, HIV‐negative pregnant women were screened for HBsAg. HBsAg‐positive mothers were stratified by HBV DNA into HVL (≥ 20,000 IU/mL), low viral load (LVL), or LVL on treatment. HVL mothers received Tenofovir Disoproxil Fumarate plus Lamivudine in the third trimester. Infants of HBsAg‐positive mothers received BD vaccination within 24 h and the 3D pentavalent series; infants of HBsAg‐negative mothers received the 3D series only. All infants were tested for HBsAg at nine months. Of 19,053 mothers screened, 3.46% were HBsAg‐positive ( n = 660). Among HVL mothers ( n = 80), 96.3% initiated antivirals; none of their infants who received both BD and 3D tested HBsAg‐positive. Among LVL mothers not on treatment ( n = 558), the prevalence of infection at nine months was 0.4% despite full vaccination. No infections occurred among LVL mothers on treatment or among infants of HBsAg‐negative mothers. Overall infant HBsAg prevalence was 0.19%, with an adjusted national estimate of 0.02%. Integrating maternal antiviral prophylaxis, targeted BD vaccination, and universal 3D vaccination achieved near‐elimination of HBV MTCT in this setting. Nationally scaling this strategy could enable Uganda to meet the WHO target of less than 0.1% infant HBV prevalence before 2030 and serve as a model for other high‐burden countries with significant rates of home births.