Achieving virological control in pan-resistant HIV-1 infection: A case series

Background HIV-I pan-resistance refers to a reduced susceptibility to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and integrase strand tranfer inhibitors. Although still anecdotal, its management remains a concern both for affected people living with HIV (PLWH) and for public health. Methods We described genotypic resistance testing (GRT) of three PLWH with a documented poor virological response to previous antiretroviral therapies, who started ibalizumab, an anti-CD4 monoclonal antibody, combined with an optimized background therapy. Both historical and most recent GRT on plasma RNA and peripheral blood mononuclear cell DNA were interpreted according to the Stanford HIVDb version 9.0 (last updated on 22 February, 2021). After the switch to a regimen including the monoclonal antibody, HIV-I RNA has been quantified biweekly (PCR Cobas (R) HIV-I test 6800 Systems, Roche Diagnostics). Follow-up was censored at data freezing (16 January, 2021). Findings We report findings from heavily treatment-experienced PLWH with a pan-resistant HIV-I infection, who achieved virological control once introduced injections of ibalizumab, that is free from cross-resistance with all the antiretroviral drugs available and ensures patient adherence due to a close monitoring attributable to the route of administration, combined with recycled enfuvirtide and an optimized background regimen, selected on the basis of an accurate evaluation of resistance mutations. Interpretation In these cases, this new approach has revealed to be a turning point in achieving virological control. Copyright (C) 2022 The Authors. Published by Elsevier B.V.