Broadly neutralizing antibody treatment maintained HIV suppression in children with favorable reservoir characteristics in Botswana
Roger Shapiro, Gbolahan Ajibola, Kenneth Maswabi, Michael D. Hughes, Bryan S Nelson, Aischa Niesar, Molly Pretorius Holme, Kathleen M. Powis, Maureen Sakoi, Oganne Batlang, Sikhulile Moyo, Terence Mohammed, Comfort Maphorisa, Kara Bennett, Zixin Hu, Françoise Giguel, Jacqueline D. Reeves, Michael A. Reeves, Ce Gao, Xu G. Yu, Margaret E. Ackerman, Adrian B. McDermott, Marlene Cooper, Marina Caskey, Lúcio Gama, Patrick Jean‐Philippe, Dwight E. Yin, Edmund V. Capparelli, Shahin Lockman, Joseph Makhema, Daniel R. Kuritzkes, Mathias Lichterfeld
Abstract
Broadly neutralizing antibodies (bNAbs) may provide an alternative to standard antiretroviral treatment (ART) for controlling HIV-1 replication and may have immunotherapeutic effects against HIV-1 reservoirs. We conducted a prospective clinical trial with two HIV-1 bNAbs (VRC01LS and 10-1074) in children ( n = 25) who had previously initiated small-molecule ART treatment before 7 days of age and who continued treatment for at least 96 weeks. Both bNAbs were dosed intravenously every 4 weeks, overlapping with ART for at least 8 weeks and then continued for up to 24 weeks or until detectable viremia of HIV-1 RNA rose above 400 copies per milliliter in the absence of ART. Eleven (44%) children maintained HIV-1 RNA below 400 copies per milliliter through 24 weeks of bNAb-only treatment; 14 (56%) had detectable viremia above 400 copies per milliliter at a median of 4 weeks. Archived HIV-1 provirus susceptible to 10-1074, lower birth HIV-1 DNA reservoir in peripheral blood mononuclear cells, sustained viral suppression throughout early life, and combined negative qualitative HIV-1 DNA polymerase chain reaction and negative HIV-1 serology at entry were associated with maintaining suppression on bNAbs alone. This proof-of-concept study suggests that bNAbs may represent a promising treatment modality for infants and children living with HIV-1. Future studies using newer bNAb combinations with greater breadth and potency are warranted.