Critical gaps in HIV-1 vertical transmission pathways – a population health perspective

Despite substantial progress in the prevention of mother-to-child transmission (PMTCT) of HIV-1, an estimated 120,000 children acquired HIV in 2024. While global antiretroviral therapy (ART) coverage among pregnant women living with HIV is high, residual transmission persists through a complex interplay of biological, health-systems, and sociostructural failures. This narrative review synthesizes literature from PubMed, WHO, and UNAIDS databases (published between 2000 and 2026) to examine critical gaps in HIV-1 vertical transmission through a population health lens. We delineate biological mechanisms across in utero, intrapartum, and postnatal pathways. Mapping the PMTCT cascade reveals consequential failure points: per UNAIDS estimates, undiagnosed maternal infection accounts for 42% of residual pediatric infections; ART interruption contributes 25%; and incident maternal infection during pregnancy and breastfeeding contributes 23%. Furthermore, structural determinants including poverty, stigma, adolescent vulnerability, and gender inequality heavily dictate PMTCT outcomes. Emerging strategies—such as long-acting injectables (lenacapavir, cabotegravir), broadly neutralizing antibodies (bNAbs), the triple elimination framework, and digital health—offer significant promise but require equitable deployment. Finally, we address the operational impact of recent disruptions to PEPFAR funding on global PMTCT infrastructure. Closing the remaining gaps in vertical transmission demands integrating biomedical tools with structural interventions and equity-focused health systems strengthening.