Imperial College London
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Professor Sarah Fidler BSc. MBBS. FRCP. PhD

Faculty of Medicine, Department of Infectious Disease

Professor of HIV and Communicable Diseases
 
 
 
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Contact

 

+44 (0)20 7594 6230s.fidler

 
 
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Location

 

clinical trial centre Winston Churchill wingMedical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Zacharopoulou:2024:10.3389/fimmu.2024.1352123,
author = {Zacharopoulou, P and Lee, M and Oliveira, T and Thornhill, J and Robinson, N and Brown, H and Kinloch, S and Goulder, P and Fox, J and Fidler, S and Ansari, MA and Frater, J},
doi = {10.3389/fimmu.2024.1352123},
journal = {Front Immunol},
title = {Prevalence of resistance-associated viral variants to the HIV-specific broadly neutralising antibody 10-1074 in a UK bNAb-naïve population.},
url = {http://dx.doi.org/10.3389/fimmu.2024.1352123},
volume = {15},
year = {2024}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Zacharopoulou,P
AU  - Lee,M
AU  - Oliveira,T
AU  - Thornhill,J
AU  - Robinson,N
AU  - Brown,H
AU  - Kinloch,S
AU  - Goulder,P
AU  - Fox,J
AU  - Fidler,S
AU  - Ansari,MA
AU  - Frater,J
DO  - 10.3389/fimmu.2024.1352123
PY  - 2024///
TI  - Prevalence of resistance-associated viral variants to the HIV-specific broadly neutralising antibody 10-1074 in a UK bNAb-naïve population.
T2  - Front Immunol
UR  - http://dx.doi.org/10.3389/fimmu.2024.1352123
UR  - https://www.ncbi.nlm.nih.gov/pubmed/38562938
VL  - 15
ER  -
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