Predictive Markers for Sustained Viral Suppression on Dual Broadly Neutralizing Antibodies During Antiretroviral Treatment Interruption in Children

Background: Simple clinical markers may predict favorable outcomes in pediatric HIV treatment and cure trials. We report findings for biomarker combinations evaluated during the broadly neutralizing antibodies (bNAbs)–only step of the Tatelo Study in Botswana. Methods: Twenty-five children on antiretroviral treatment since birth received up to 24 weeks of bNAb-only treatment (VRC01LS + 10-1074). Suppression was defined as maintaining HIV RNA <400 copies/mL. HIV qualitative DNA and HIV RNA were performed every 1–2 weeks and enzyme immunoassay (EIA) every 4–8 weeks. Results: The median age of children at study entry was 3.7 years [interquartile range (IQR) 3.1–4.4]. At the start of bNAb-only treatment, 13/25 (52%) had negative qualitative DNA, 17/25 (68%) had negative EIA, and 10/25 (40%) were negative for both. Nine of 13 (69%) with negative qualitative DNA remained suppressed compared with 2/12 (17%) with positive or indeterminate qualitative DNA [odds ratio (OR) 11.3, 95% confidence interval (CI): 1.7 to 76.9]. Nine of 17 (53%) with negative EIA remained suppressed compared with 2/8 (25%) with positive EIA (OR 3.4, 95% CI: 0.5 to 21.7). Combining biomarkers, 8/10 (80%) who were negative/negative remained suppressed, compared with 3/15 (20%) with any other pattern (OR 16.0, 95% CI: 2.2 to 118.3). In the visit immediately before rebound, HIV RNA target detection occurred in 1/14 (7%) of failures. Conclusion: At the start of bNAb-only treatment, negative qualitative DNA, and especially negative/negative DNA and EIA, have potential to predict maintenance of viral suppression among children on dual bNAbs. HIV RNA target detection below the assay limit did not prove to be a clinically useful biomarker in the visits preceding rebound.