Several anti-HIV-1 broadly neutralizing antibodies (bNAbs) targeting different envelope epitopes are being evaluated as long-acting alternatives or adjuvants to antiretrovirals (ART) for prevention and therapy, or as part of remission strategies. The combination of 3BNC117 and 10-1074 induced significant reductions in viremia and maintained viral suppression during ART interruption in individuals harboring antibody-sensitive viruses. Here, we evaluated the antiviral activity of the long-acting (LS) versions of these bNAbs during viremia.
This open-label phase 1 study enrolled adults with chronic HIV not on ART, with plasma HIV-1 RNA ranging from 2.7-5.0 log10 cp/ml, to receive single 30 mg/kg infusions of 3BNC117-LS and 10-1074-LS. Study endpoints were safety, pharmacokinetics, and effects on viremia, and follow up was of 24 weeks. Antibody sensitivity of circulating viruses was determined post-hoc by the PhenoSense mAb Assay. This phenotypic assay can generate HIV-1 pseudovirions expressing populations of plasma HIV-1 envelope sequences which are tested for neutralization sensitivity to bNAbs.
Six male participants were enrolled with median baseline plasma HIV-1 RNA of 4.7 log10 cp/ml ( range 3.0-5.4 log10 cp/ml). Antibody infusions were generally well tolerated. All 6 participants experienced decline in plasma HIV-1 RNA, with a median maximum decline of 1.86 log10 cp/ml (range = 1.1-2.49 and SD = 0.48 log10 cp/ml) reached at a median of 1.5 weeks following infusions. The observed magnitude of the decrease in viremia was similar to that observed after infusions of the unmodified 3BNC117 and 10-1074 (p 0.81). The decreased viremia was transient in 4 participants with baseline resistance in plasma to either 3BNC117-LS or 10-1074-LS, which means they effectively received functional monotherapy. In contrast, the 2 participants with plasma viruses that were sensitive to both antibodies and baseline plasma HIV-1 RNA of 3 and 3.5 log10 cp/ml achieved and maintained undetectable HIV-1 RNA levels for the 24 weeks of follow up and > 12 weeks in the second participant who remains on study.
In this pilot study, the long-acting (LS) 3BNC117 and 10-1074 combination preserved antiviral activity and the potential to maintain long-term viral suppression in participants with sensitive viruses. Baseline antibody sensitivity of plasma viruses determined by the PhenoSense mAb Assay correlated with viremia decline and long-term suppression.