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

• Published in: Frontiers in immunology 2024-03, Vol.15, p.1352123-1352123
• Main Authors: Zacharopoulou, Panagiota, Lee, Ming, Oliveira, Thiago, Thornhill, John, Robinson, Nicola, Brown, Helen, Kinloch, Sabine, Goulder, Philip, Fox, Julie, Fidler, Sarah, Ansari, M Azim, Frater, John
• Format: Article
• Language: English
• Subjects: 10-1074; Antibodies, Neutralizing; broadly neutralising antibodies; Broadly Neutralizing Antibodies; env Gene Products, Human Immunodeficiency Virus - genetics; Epitopes; HIV - human immunodeficiency virus; HIV Antibodies; HIV Infections - drug therapy; HIV Infections - epidemiology; HIV-1 - genetics; Humans; Immunology; Prevalence; primary HIV infection (PHI); resistance screening; United Kingdom - epidemiology
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1352123

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 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.