Long-Term Clinical, Immunologic, and Viral Reservoir Outcomes in Children Treated With VRC01LS and 10-1074 Monoclonal Antibodies in the Tatelo Study.

BACKGROUND

Broadly neutralizing antibodies (bNAbs) are a promising treatment option for children with HIV-1, but their long-term impact on virologic, immunologic, and clinical outcomes is unknown.

METHODS

The Tatelo Study investigated dual bNAbs as an alternative to standard antiretroviral treatment (ART) in children. Children received bNAb-only treatment for 24 weeks (or until detectable viremia ≥400 copies/mL occurred) and were followed initially through 24 weeks after restarting ART. We continued follow-up from 24 to 96 weeks post-bNAb intervention to identify the long-term clinical, immunologic, and viral reservoir outcomes.

RESULTS

Median age at the start of long-term follow-up was 4.9 years (range 3.4, 6.8 years). From 23.0 to 43.6 weeks post-bNAb intervention, all 25 children transitioned to dolutegravir-based ART; 3 (12%) had a single episode of HIV-1 RNA ≥ 40 copies/mL after starting the DTG-based regimen and re-suppressed with adherence counseling on the same regimen. There were no grade 3 or 4 events, and no child died. Absolute CD4 cell counts remained stable at 96 weeks post-bNAb intervention (median: 1130 cells/mm3, IQR: 840, 1249 cells/mm3), and clinical biomarkers (serology, qualitative HIV DNA) were stable. At last available sampling, only 8 (32%) participants had detectable intact provirus (5 had rebounded during the bNAb-only intervention phase), with a low median HIV-1 DNA in PBMCs of 0.39 log10 (range 0.1 to 3.8 log10) copies/106 cells.

CONCLUSIONS

There was no long-term impact on safety, clinical, immunologic, or virologic outcomes after bNAb-only treatment, including for children who rebounded during the intervention. These findings support further bNAb treatment trials in children.

CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov, NCT03707977, https://clinicaltrials.gov/.