Abstract Body


Various anti-HIV immunotherapy strategies have been associated with ART-free control in non-human primates. We sought to determine whether a combination of such strategies could affect virologic control in people with HIV after ART discontinuation.


We performed a single-arm proof-of-concept study to evaluate the efficacy of a combination approach involving (1) Gag conserved element (CE)-targeted DNA+IL-12 prime/MVA boost vaccination, followed by (2) a combination of two broadly neutralizing antibodies (bNAbs; 10-1074, VRC07-523LS) and a TLR-9 agonist (lefitolimod) and then (3) two bNAbs given at the time of treatment interruption. Seven of the 10 participants (9 cisgender men, 1 transgender woman) had initiated ART within 6 months of HIV infection. We defined the set point as the median of all values off ART beginning 2 weeks after peak rebound. We measured bNAb sensitivity using the PhenoSense assay and T cell responses by intracellular cytokine staining.


Viral rebound occurred on average 15 weeks after ART interruption and median ATI length was 37 weeks. Notably, 7/10 exhibited atypical rebound dynamics characterized by non-exponential growth and/or oscillations; 5/10 had set points < 1000 copies/mL and 7/10 < 5000 copies/mL. One individual has not experienced rebound as of 18 months off ART, with low levels of non-intact provirus in gut tissue and intermittent detection below the quantification limit of HIV DNA and RNA in PBMCs during the ATI. Higher bNAb exposure (AUC) was associated with a later time to rebound (p=0.054 and p=0.052 for VRC07-523LS and 10-1074, respectively), but bnAb levels at rebound were highly variable across participants (1.3-38.3 mcg/mL for 10-1074, 0.2-57.9 mcg/mL for VRC07-523LS). Phenotypic susceptibility to both 10-1074 and VRC07-523LS declined over time. The vaccine regimen increased the magnitude of IFNg+ CE-specific CD4+ and CD8+ T cell responses in all 10 participants between pre-vaccination and 2-weeks post-boost (median CD4: 0.03% vs 0.341% [p=0.002]; CD8: 0.026% vs 0.158% [p=0.002]). Neither antibody levels nor associated susceptibility could completely explain the variability in post-ART set points, suggesting the involvement of other factors.


The majority of individuals who received combination immunotherapy exhibited evidence of virologic control post-ART. Treatment-mediated virologic and immunologic factors may have contributed to this outcome.

A. Study schematic. B. Plasma HIV RNA during ATI timed from initial rebound in each participant and (inset) time to initial rebound for each participant.