Prevalence of resistance-associated viral variants to the HIV-specific broadly neutralising antibody 10-1074 in a UK bNAb-naïve population.

Autor:	Zacharopoulou P; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Lee M; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Department of Infectious Disease, Imperial College London, London, United Kingdom., Oliveira T; Laboratory of Molecular Immunology, Rockefeller University, New York, NY, United States., Thornhill J; Department of Infectious Disease, Imperial College London, London, United Kingdom., Robinson N; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Brown H; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Kinloch S; Institute of Immunity and Transplantation, Royal Free Hospital, London, United Kingdom., Goulder P; Department of Paediatrics, University of Oxford, Oxford, United Kingdom., Fox J; Department of Infection, Guys and St Thomas' NHS Trust, London, United Kingdom., Fidler S; Department of Infectious Disease, Imperial College London, London, United Kingdom., Ansari MA; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Frater J; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Oxford National Institute of Health Biomedical Research Centre, Oxford, United Kingdom.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Mar 18; Vol. 15, pp. 1352123. Date of Electronic Publication: 2024 Mar 18 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1352123
Abstrakt:	Broadly neutralising antibodies (bNAbs) targeting HIV show promise for both prevention of infection and treatment. Among these, 10-1074 has shown potential in neutralising a wide range of HIV strains. However, resistant viruses may limit the clinical efficacy of 10-1074. The prevalence of both de novo and emergent 10-1074 resistance will determine its use at a population level both to protect against HIV transmission and as an option for treatment. To help understand this further, we report the prevalence of pre-existing mutations associated with 10-1074 resistance in a bNAb-naive population of 157 individuals presenting to UK HIV centres with primary HIV infection, predominantly B clade, receiving antiretroviral treatment. Single genome analysis of HIV proviral envelope sequences showed that 29% of participants' viruses tested had at least one sequence with 10-1074 resistance-associated mutations. Mutations interfering with the glycan binding site at HIV Env position 332 accounted for 95% of all observed mutations. Subsequent analysis of a larger historic dataset of 2425 B-clade envelope sequences sampled from 1983 to 2019 revealed an increase of these mutations within the population over time. Clinical studies have shown that the presence of pre-existing bNAb mutations may predict diminished therapeutic effectiveness of 10-1074. Therefore, we emphasise the importance of screening for these mutations before initiating 10-1074 therapy, and to consider the implications of pre-existing resistance when designing prevention strategies. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Zacharopoulou, Lee, Oliveira, Thornhill, Robinson, Brown, Kinloch, Goulder, Fox, Fidler, Ansari and Frater.)
Databáze:	MEDLINE
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