@article{McCormack_M-2025_210954,
title = {Retrovirus-based pseudotyped virus neutralisation assays overestimate neutralising activity in sera from participants receiving integrase inhibitors},
author = {McCormack, M. and Asamaphan, P. and Hughes, E. and Banda, L. and Kasenda, S. and Davis, C. and Szemiel, A. and Crampin, A. and Amoah, A. and Thomson, E. and Ho, A. and Willett, B.},
month = {aug},
year = {2025},
abstract = {Retroviral pseudotype-based virus neutralisation assays are widely used to estimate functional immunity, but may be unsuitable for testing human immunodeficiency virus (HIV)-infected individuals receiving integrase inhibitor treatment. We evaluated these assays for measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and hepatitis C virus (HCV) neutralisation in people living with HIV. SARS-CoV-2 neutralisation was assessed using HIV-based SARS-CoV-2 pseudoviruses in sera from a longitudinal Malawian cohort (n = 1,876), detecting neutralisation across timepoints in 10.5–54.5% of HIV-uninfected vs. 85.5–93.9% of HIV-infected participants (n = 96). HIV-infected sera were re-tested using vesicular stomatitis virus (VSV)-based SARS-CoV-2 pseudoviruses, estimating seroprevalence at 5.6–65.2%, suggesting HIV-based assays overestimate neutralisation. HIV-based VSV-glycoprotein(G) pseudoviruses confirmed non-specific inhibition in 75.0-87.9% of HIV-infected participants. HCV neutralisation was assessed in UK-based HCV patients (n = 100, n = 90 HIV-infected) using murine leukaemia virus (MLV)-based HCV pseudoviruses. Non-HCV-specific inhibition was detected in integrase inhibitor recipients. Median neutralisation of MLV(HCV) pseudoviruses was higher in integrase inhibitor recipients (71.8% vs. 21.3%). Testing HIV(SARS-CoV-2) and MLV(HCV) pseudoviruses against antiretroviral drugs showed interference by integrase inhibitors (specifically, dolutegravir). Isolating IgG from serum removed the interference by residual drugs. Retrovirus-based assays are therefore unsuitable for testing individuals receiving integrase inhibitors. Protective immunity to viruses has likely been over-reported in HIV prevalent populations.},
volume = {15},
journal = {Scientific Reports},
publisher = {Springer Nature},
url = {https://doi.org/10.1038/s41598-025-11362-7},
}
