HIV broadly neutralizing antibodies for children: implementation barriers in low-income settings.

PURPOSE OF REVIEW: Broadly neutralizing monoclonal antibodies (bNAbs) represent a transformative frontier for the prevention, treatment, and potential remission of HIV in children. Given that over 95% of the pediatric population living with or at risk for HIV resides in low-income and middle-income countries (LMICs), prioritizing trials and implementation in these regions is an ethical and clinical imperative. This review identifies the primary structural, biological, and regulatory barriers that must be addressed to ensure equitable global access to bNAb-based interventions.

RECENT FINDINGS: Recent trials in Africa suggest that dual-bNAb combinations can maintain viral suppression in children during ART interruptions and restrict the viral reservoir. While the lower weight-based dosing requirements in neonates and infants present a cost-effective advantage for pediatric HIV management, several scientific and implementation challenges persist. Biological barriers, such as substantial pre-existing resistance to specific bNAbs within HIV-1 Clade C isolates, necessitate region-specific combination therapies, which in turn increase manufacturing and programmatic complexity. Furthermore, pharmacokinetic modeling indicates that elevated viral loads accelerate bNAb clearance, directly influencing optimal dosing strategies and highlighting a critical implementation gap in settings with limited viral load monitoring. Current trials in children are notably behind those in adults, with a lack of confirmatory efficacy data. These biological and clinical challenges are further limited by operational challenges, including climate-driven issues and infrastructure deficits that threaten the cold-chain logistics essential for biologic distribution, posing significant barriers to equitable global access.

SUMMARY: While bNAbs offer a promising path toward HIV remission and simplified prevention, their success in LMICs depends on overcoming specific implementation barriers. Addressing these challenges is essential to prevent a delayed and inequitable deployment of these therapies to children in need. All stakeholders within the process from discovery to final implementation need to be involved for an appropriate implementation.