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Altered Viral Kinetics at ATI After Dual LS-bNAbs Plus ART: A Preliminary Analysis of RIO Arm B
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CROI 2026 Feb 22-25 Denver
Julia Edgar1, Tamara Elliott2, Ming Lee2, Louise-Rae Cherrill2, Emanuela Falaschetti2, Panagiota Zacharopoulou1, Timothy Tipoe3, Simon Collins4, Marcilio Jorge Fumagalli5, Graham Taylor2, Kelly Seaton6, Marina Caskey5, Michel Nussenzweig5, Sarah Fidler2, John Frater1, for the RIO Trial Investigators
1University of Oxford, Oxford, UK, 2Imperial College London, London, UK, 3The Chinese University of Hong Kong, Hong Kong, Hong Kong, 4HIV i-Base, London, UK, 5The Rockefeller
program abstract
Background: Therapeutic levels of broadly neutralizing antibodies (bNAbs) can sustain undetectable HIV viraemia. We investigated if post-bNAb control persists after an ART-protected ‘wash-out’ period. In the RIO trial, Arm B participants initially received placebo during a first analytical treatment interruption (ATI-1). Following rebound, participants resumed ART and were offered 3BNC117-LS and 10-1074-LS, and later underwent a second ATI (ATI-2), allowing analysis of viral control when bNAbs had waned.
Methods: Thirty-four participants (18-60 years) were randomized to placebo in Arm B and underwent ATI-1. After rebound, participants resumed ART and received 1-2 bNAb doses (>20wks apart), then underwent ATI-2 a median
6.5 months post-last dose. HIV viral load (VL) was measured weekly during ATI, and within-subject comparisons were made between ATI-1 and ATI-2 for participants who initiated ATI-2, including viral doubling time (DT), peak VL, and
HIV-specific IFN-y ELISpot responses. PK analysis of bNAb levels was measured by ELISA. Parameters were compared between early rebound (≤9 weeks; threshold defined by ATI-1 rebound mean+2SD) vs delayed rebound (>9 weeks) in ATI-2.
Results: Of 34 Arm B participants, 29 rebounded in ATI-1, resumed ART, and received bNAbs (3 withdrew; 2 undetectable VL>3 yrs), and 25/29 have initiated ATI-2 to date. At ATI-2 start, median modelled serum levels of 10-1074-LS and 3BNC117-LS were 40.2 and 43.6 ug/mL, respectively - similar to levels observed at rebound in Arm A. No anti-drug antibodies were detected. Compared to ATI-1, ATI-2 showed lower median peak VL (21,400 vs 100,000 cps/mL, p=0.001), and slower median viral DT (0.57 vs 0.31 weeks, p=0.04). Two rebound phenotypes emerged in ATI-2: 12/25 participants showed early rebound with viral kinetics similar to ATI-1, with viral rebound (VL x6>1000 or x2>100,000 cps/mL) within 9 weeks of ATI, and no difference in ATI-2 peak VL or viral DT. In contrast, 13/25 participants demonstrated delayed rebound with sustained control >9 weeks, and significantly lower ATI-2 median peak VL (3,895 vs 19,700 cps/mL, p=0.004) and slower median viral DT (1.16 vs 0.35 weeks, p=0.02) compared to ATI-1. ATI-1 viral kinetics, and bNAb levels and IFN-y ELISpot T cell responses at ATI-2 start, were comparable between rebound phenotypes.
Conclusions: Over half of RIO Arm B participants to date demonstrated delayed rebound and attenuated viral kinetics during ATI-2, suggesting a shift in hostviral dynamics consistent with post-bNAb HIV inhibition.
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