VRC01 with antiretroviral initiation in infants is well tolerated, and higher concentrations associate with greater HIV-1 DNA declines.

Antiretroviral therapy (ART) in infancy restricts the HIV-1 reservoir but is insufficient for ART-free remission. We hypothesized that broadly neutralizing antibodies (bNAbs) administered at the initiation of ART would be safe and reduce HIV-1 DNA in peripheral blood cells more than ART alone. In a randomized, open-label two-arm study of infants with HIV-1 within 14 days of ART initiation, 30 infants received subcutaneous VRC01 (40 milligrams per kilogram), a bNAb that targets the CD4-binding site of gp120, at weeks 0, 2, 6, and 10, whereas 31 participants received no VRC01. VRC01 was well tolerated with no safety concerns. Decreases in HIV-1 DNA from weeks 0 to 14 were not different between arms overall nor when adjusted for a priori-defined covariates, including baseline resistance to VRC01. Baseline VRC01 resistance and resistance to prescribed ART were detected in a subset of infants treated with VRC01. Plasma VRC01 trough concentrations were below those predicted by pretrial modeling based on studies of infants exposed but uninfected with HIV-1. No anti-VRC01 antibodies were detected to account for low VRC01 concentrations. In post hoc analyses, higher plasma HIV-1 RNA values correlated with lower plasma VRC01 concentrations, whereas larger reductions in HIV-1 DNA were associated with higher VRC01 concentrations and lower plasma HIV-1 RNA, suggesting a concentration-dependent effect of bNAb treatment on HIV-1 DNA. These results highlight the safety of bNAbs for treatment of infants. Studies with more potent bNAbs are needed to assess effects on HIV-1 DNA during early treatment of infants living with HIV-1.