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Teropavimab and Zinlirvimab Sensitivity in People Living With MDR HIV-1: PRESTIGIO Registry Data

Background: Broadly neutralizing antibodies (bNAbs) are being investigated
as long-acting antiviral therapies, but sensitivity to bNAbs in persons with
multidrug-resistant HIV is unknown. Here, we characterized sensitivity to
teropavimab (GS-5423; 3BNC117-LS; TAB) and zinlirvimab (GS-2872; 10-1074-LS;
ZAB) in people living with 4-class drug-resistant HIV (4DR-PWH).
Methods: Multicenter, observational study using plasma or peripheral blood
mononuclear cells collected from 50 4DR-PWH (25 with HIV-1 RNA > 1000
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 (NRTI, NNRTI, PI and INSTI). Phenotypic
sensitivity to bNAbs was determined using the PhenoSense Monoclonal
Antibody assay (Monogram), with susceptibility defined as IC90 ≤2 µg/mL.
Descriptive statistics are used to present results. Spearman's rank test used for
associations between phenotypic susceptibility and clinical variables.
Results: Characteristics of included individuals with analyzed samples
were indicative of extensive treatment history (Table1). 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; 7 (15%) had
phenotypic resistance to both bNAbs. Of 22 viremic participants, 19 (86%)                                                    were phenotypically sensitive to TAB, 10 (45%) to ZAB, 9 (41%) to both bNAbs,
and 2 (9%) to neither. Of 24 participants with virologic suppression, 67%
were phenotypically sensitive to TAB, 54% to ZAB, 42% to both bNAbs, and
5 (21%) to neither. The proportion of participants with sensitivity to both
bNAbs was similar (p=0.99) in viremic participants (9/22 [41%]) compared to
those with virologic suppression (10/24 [42%]). Nonsignificant correlations
between phenotypic sensitivity to bNAbs and age, years of ART, CD4+ cell
count, HIV-RNA, type of ART regimen at the sample collection, viral tropism
and HIV subtype. There were marginal correlations between phenotypic
sensitivity to TAB and years since HIV diagnosis (Spearman r= 0.287, p=0.053)
and phenotypic sensitivity to ZAB and CD8+cell count (Spearman r= -0.317,
Conclusion: A significant number of the analyzed 4DR-PWH 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

Dated Sun Mar 03 2024

Authors: V.Spagnuolo, L.Galli, A.Parvangada, K.J.Dunn, F.Lagi, R.Gagliardini, L.Sarmati, A.Cattelan, A.Giacomelli, M.M.Santoro, M.Zazzi, C.Callebaut, A.Castagna, L.VanderVeen

Affiliations: .