Background
Broadly neutralizing antibodies (bNAbs) may reduce viral reservoir and promote post-treatment HIV control; establishing their ability to sustain viral suppression is an essential first step toward the goal of drug-free remission. The Tatelo Study found nearly half of unscreened children on ART since birth remained suppressed on dual bNAbs alone (10-1074 and VRC01LS). In the ongoing Tatelo Plus Study (IMPAACT 2042), we evaluated triple bNAbs (VRC07-523LS, PGDM1400LS, and PGT121.414.LS) after pre-screening for viral susceptibility and clinical biomarkers.
Methods
Tatelo Plus (IMPAACT 2042) is a single arm, open-label Phase I/II trial evaluating combination bNAbs for treatment and possible drug-free remission in children who started ART near birth in Botswana. Participants received bNAbs and ART for 32 weeks (Step 1). ART was interrupted during a 24-week bNAb-only phase (Step 2) for suppressed children who had either 1) phenotypic susceptibility to at least 2 of the 3 bNAbs (LabCorp, USA), or 2) if susceptibility testing was unsuccessful, had negative qualitative HIV DNA PCR and negative HIV serology (biomarker criteria). Full susceptibility was defined as 90% inhibitory concentration (IC90) ≤1.0 µg/mL and maximum percent inhibition (MPI) ≥98%, and partial susceptibility defined as IC90 1.1-10 µg/mL and MPI ≥98%. Intravenous bNAb infusions were administered at 4-weekly visits (VRC07-523LS every visit, PGDM1400LS or PGT121.414.LS on alternate visits).
Results
Of 12 children (median age 8 [range 2, 10] years) who completed Step 1, all maintained viral suppression <40 copies/mL, and 8 (67%) had successful phenotypic testing; of these 6 (75%) were fully or partially susceptible to at least two bNAbs and were eligible for Step 2. The 4 children with unsuccessful phenotypic testing were all eligible for Step 2 by biomarker criteria. At Step 2 entry, 7 (70%) of 10 children continued to receive all three bNAbs, and 3 (30%) received two bNAbs (full resistance detected to the third bNAb). All 10 participants (100%; 95% CI 69%, 100%) maintained plasma HIV RNA <40 copies/mL throughout the entire 24-week bNAb-only period.
Conclusions
Among the first 10 Tatelo Plus participants to receive dual- or triple bNAb-only treatment, all maintained complete viral suppression for 24 weeks. Combination bNAb treatment following phenotypic screening or negative biomarker criteria may serve as an ART interruption strategy and a practical first step for future drug-free remission studies in children.