Background
Non-human primate (NHP) models of HIV cure using HIV-specific broadly neutralising antibodies (bNAbs) describe viral control after an initial period of rebound, attributable to HIV-specific T cell responses – a ‘vaccinal effect’. There are examples of viral control after bNAbs in human studies, but no cases of post-bNAb viral rebound followed by sustained suppression, which may indicate new immunity.
Methods
We report a 38-yr old male participant enrolled in the RIO trial. At HIV seroconversion in 2017 he had an initial HIV VL of 55,338 copies/ml before commencing ART 18 days later. Virally suppressed on ART until enrolling into RIO in 2021, he received a placebo infusion and stopped ART; his HIV VL rebounded 4 weeks later (peak 6225 copies/ml). He then received one dose of dual bNAbs (10-1074LS; 3BNC117LS) and ART for 6 months. ART was then stopped again 24 weeks later for a second TI. HIV VL rebounded within 5 weeks and viraemia was sustained for 20 weeks (peak 1893 copies/ml). He then spontaneously controlled (<20 copies/ml) and has maintained aviraemia for 80 weeks since (Figure). During this period bNAb PK levels were both <10ug/ml and ART agents were undetectable in plasma. We present HIV reservoir measures (Q4PCR), HIV Env sequencing and T cell responses measured by ELISPOT, proliferation, AIM and CBA to explore the mechanisms of remission.
Results
The participant showed relative sensitivity to 10-1074 at baseline (4/22 resistant SGA Env sequences; IC80s 0.31-2.2ug/ml) and rebounded during the 2nd TI with 100% resistant sequences (IC80s >50ug/ml) after bNAbs. He developed new T cell responses to a sub-dominant C*07:01 epitope in Nef (KRQDILDLWVY) and a dominant likely B42:01-restricted epitope in Gag p24 (GPAHKARVL) which peaked 37 weeks after TI (400 spots/106), but then waned. Control was associated with increased Gag-specific CD8 T cell proliferation (4.5% at peak vs 0.8% at baseline), Gag-specific CD4 AIM responses (0.4% at peak vs 0% at baseline) and Granzyme B, IL-2 and TNFa by CBA after Gag stimulation. We detected no autologous antibody neutralisation prior to bNAbs. Reservoir size decreased from 2.1 to 0.58 intact proviral DNA copies/million CD4 T cells at baseline versus 37 weeks post-2nd TI (Q4PCR). We will report analyses of integration sites, serology and viral outgrowth.
Conclusions
This is the first reported example of remission following a period of rebound after bNAb dosing and non-therapeutic bNAb levels, consistent with the vaccinal effect seen in NHP studies.
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