Use of broadly neutralizing antibodies in pediatric HIV for treatment and remission

Abstract

Purpose of review: The evolving landscape of HIV treatment for children now extends beyond viremic control with daily antiretroviral treatment (ART), with new approaches that sustain viral suppression while permitting breaks from small molecule ART now reaching the clinical trial stage. Trials involving broadly neutralizing monoclonal antibodies (bNAbs) have commenced in selected pediatric populations. Evidence from adult bNAb studies suggests that bNAbs might reduce latent viral reservoirs, fostering hope that these agents could offer a pathway to posttreatment control, which is seldom achievable with small molecule ART.

Recent findings: Few pediatric studies to date have used bNAbs in the setting of existing HIV infection to improve treatment outcomes. Safety and pharmacokinetic (PK) data from IMPAACT 2012, IMPAACT 2008, and the Tatelo Study have been reassuring. The Tatelo Study in Botswana first used combination bNAbs (VRC01LS, 10-1074) as an alternative treatment strategy in children aged 2-5 years who started ART near birth, showing that nearly half of unscreened children could maintain viral suppression with dual bNAbs alone, and identifying predictors for success. From a viral reservoir standpoint, IMPAACT 2008 identified a possible dose-dependent effect of VRC01, with higher plasma VRC01 concentrations being associated with lower HIV-1 DNA. Further reservoir data are expected from Tatelo Plus (IMPAACT 2042), which began enrolling in 2024 and will evaluate a triple bNAb combination (VRC07-504LS, PGDM1400LS, and PGT.121.LS) with the addition of an analytic treatment interruption (ATI) in some children. IMPAACT P1115, which recently reported successful ATI in selected low-reservoir children, is evaluating the addition of VRC01 or VRC-07-523LS on viral reservoir and treatment outcomes. Looking to the future, IMPAACT 2039 will evaluate VRC07-523LS + PGT121.414LS as part of a combination intervention, and the SNOW study will evaluate VRC07-523LS during a series of ATIs.

Summary: This review synthesizes data for ongoing and planned pediatric bNAb treatment studies, focusing on available trial results that underscore the ability of newer and more potent long-acting bNAbs to sustain viral suppression. We discuss the potential impact of bNAbs to reduce the latent viral reservoir and their use as a strategy to achieve viral remission in children with HIV.

Keywords: ART-free treatment strategies; HIV-1 cure; broadly neutralizing monoclonal antibodies; maintenance of viral suppression; review; viral remission.