Teropavimab and zinlirvimab sensitivity in people living with multidrug-resistant HIV-1: data from the PRESTIGIO Registry

We characterized sensitivity to teropavimab (TAB) and zinlirvimab (ZAB) in people living with four-class drug-resistant HIV (4DR-PWH). This was a multicenter, observational study using plasma or peripheral blood mononuclear cells collected from 50 4DR-PWH (25 with HIV-1 RNA > 1,000 copies/mL matched by age, sex, nadir CD4+, and years on ART to 25 virologically suppressed [HIV-1 RNA < 50 copies/mL]) enrolled in the PRESTIGIO Registry (NCT04098315) with a documented 4DR (NRTIs, NNRTIs, PIs, and INSTIs). Phenotypic sensitivity to bNAbs was determined using the PhenoSense monoclonal antibody assay (Monogram), with susceptibility defined as IC90 <= 2 g/mL. The HIV-1 envelope was genotyped by next-generation sequencing, and sequences were analyzed for the presence of multi-position HIV-1 envelope amino acid signatures associated with in vitro phenotypic susceptibility to TAB and ZAB. Of 46/50 (92%) participants with PhenoSense mAb assay results, 35 (76%) were phenotypically sensitive to TAB, 23 (50%) to ZAB, and 19 (41%) to both bNAbs; seven (15%) were phenotypically resistant to both bNAbs. The proportion of individuals with sensitivity to both bNAbs was similar in participants with viremia (41%) and those with virologic suppression (42%; P = 0.99). We observed marginal correlations between TAB 90% inhibitory concentration (IC90) values and years since HIV diagnosis at the time of sample collection (Spearman r = 0.29, P = 0.05) as well as between ZAB IC90 values and CD8+ cell count (Spearman r = -0.32, P = 0.05). A significant number of the 4DR-PWH analyzed were found to have virus susceptible to TAB and ZAB. These data provide proof-of-concept that selected multidrug-resistant PWH may be candidates for future trials investigating bNAbs-containing regimens to achieve or maintain virologic suppression.