Background:
Passive administration of HIV-1 broadly neutralizing antibodies (bNAbs) can achieve durable viral suppression when replacing ART. Previous studies have suggested that ART substitution with bNAb administration can have a vaccinal effect on HIV-specific T cells, increasing response frequencies and improving functional properties during bNAb-mediated suppression. Here, we evaluated whether such a vaccinal effect occurred in the BEAT2 clinical trial, which tested a 26-week combination of bNABs (3BNC117 and 10-1074) and peg-IFN-α2b (IMM-Tx) off-ART, followed by an off-IMM-Tx follow-up non-intervention ATI (non-int. ATI).
Methods:
Cryopreserved peripheral mononuclear cells were obtained from the BEAT2 study (NCT03588715) in which baseline bNAb-sensitive PLWH received 29 weekly doses of peg-IFN-α2b (1.5µg/kg) (4 wks on ART and 26 wks off ART), and seven IV infusions of the bNAbs 3BNC117 and 10-1074 (30 mg/kg during the 26 wks off ART). Ten participants received combined IMM-Tx, and one received only bNAbs infusions. Activation-induced marker (AIM) assay and flow cytometry were used to quantify HIV-specific immune responses in all 11 donors at several time points, including baseline (on ART), after 4x weekly peg-IFN-α2b on ART, after 26 weeks of IMM-Tx (7 bNABs infusions plus peg-IFN-α2b), and during the final non-int. ATI. HIV1-specific CD4+ or CD8+ T cells were identified as CD69+PDL1+ or CD69+CD137+ or PDL1+CD137+ after stimulation against HIV-1 Consensus B Gag peptide pool.
Results:
We found no increase in Gag-specific CD4+ and CD8+ T cell responses during IMM-Tx (with or without peg-IFN-α2b) compared to baseline in most donors; increased CD8+ responses after peg-IFN-α2b were observed in a single participant. However, we did find an increase in the proportion of Gag-specific CD4+ and CD8+ T cells in 4 out of 11 individuals during the post-IMM-Tx non-int. ATI compared to earlier time points. These individuals showed sustained control of viremia (Viral load 20 c/ml for 3 participants and < 2000 c/ml for 1), suggesting an association between emerging T cell response and control of the viremia.
Conclusions:
We found no detectable change in HIV-specific T cell responses after 26 weeks of IMM-Tx with 3BNC117+10-1074 bNAB plus peg-IFN-α2b immunotherapy; however, an increase in Gag-specific T cell responses was associated with viral control following the end of IMM-Tx in a subset of persons, suggesting a potential link between IMM-Tx and T cell-mediated responses in viral suppression.