Treatment with integrase inhibitors alters SARS-CoV-2 neutralization levels measured with HIV-based pseudotypes in people living with HIV

Torre Tarazona, Humberto Erick de laGonzález Robles, AlbaCascajero, AlmudenaJiménez, PalomaMiró Meda, José M. (José María), 1956-Sánchez-Palomino, SonsolesAlcamí, JoséBuzón, María J.García Pérez, JavierHospital Clinic HIV Investigators2023-03-282023-03-282023-02-020146-6615https://hdl.handle.net/2445/196118The presence of neutralizing antibodies (NAbs) is a major correlate of protection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Thus, different in vitro pseudoviruses-based assays have been described to detect NAbs against SARS-CoV-2. However, the determination of NAbs against SARS-CoV-2 in people living with HIV (PLWH) through HIV-based pseudoparticles could be influenced by cross-neutralization activity or treatment, impeding accurate titration of NAbs. Two assays were compared using replication-defective HIV or VSV-based particles pseudotyped with SARS-CoV-2 spike to measure NAbs in COVID-19-recovered and COVID-19-naïve PLWH. The assay based on HIV-pseudoparticles displayed neutralization activity in all COVID-19-recovered PLWH with a median neutralizing titer 50 (NT50) of 1417.0 (interquartile range [IQR]: 450.3-3284.0), but also in 67% of COVID-19-naïve PLWH (NT50: 631.5, IQR: 16.0-1535.0). Regarding VSV-pseudoparticles system, no neutralization was observed in COVID-19-naïve PLWH as expected, whereas in comparison with HIV-pseudoparticles assay lower neutralization titers were measured in 75% COVID-19-recovered PLWH (NT50: 100.5; IQR: 20.5-1353.0). Treatment with integrase inhibitors was associated with inaccurate increase in neutralization titers when HIV-based pseudoparticles were used. IgG purification and consequent elimination of drugs from samples avoided the interference with retroviral cycle and corrected the lack of specificity observed in HIV-pseudotyped assay. This study shows methodological alternatives based on pseudoviruses systems to determine specific SARS-CoV-2 neutralization titers in PLWH.8 p.application/pdfengcc-by (c) Torre Tarazona, Erick de la et al., 2023http://creativecommons.org/licenses/by/3.0/es/SARS-CoV-2Inhibidors de la integrasaVIH (Virus)NeutralitatPersones seropositivesSARS-CoV-2Integrase inhibitorsHIV (Viruses)NeutralityHIV-positive personsTreatment with integrase inhibitors alters SARS-CoV-2 neutralization levels measured with HIV-based pseudotypes in people living with HIVinfo:eu-repo/semantics/article7296112023-03-28info:eu-repo/semantics/openAccess36727646