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Enhanced surveillance of HIV-1 drug resistance in recently infected MSM in the UK

Cunningham, E; Chan, YT; Aghaizu, A; Bibby, DF; Murphy, G; Tosswill, J; Harris, RJ; ... Mbisa, JL; + view all (2016) Enhanced surveillance of HIV-1 drug resistance in recently infected MSM in the UK. Journal of Antimicrobial Chemotherapy , 72 (1) pp. 227-234. 10.1093/jac/dkw404. Green open access

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Abstract

OBJECTIVES: To determine the prevalence of inferred low-frequency HIV-1 transmitted drug resistance (TDR) in MSM in the UK and its predicted effect on first-line therapy. METHODS: The HIV-1 pol gene was amplified from 442 newly diagnosed MSM identified as likely recently infected by serological avidity testing in 2011-13. The PCR products were sequenced by next-generation sequencing with a mutation frequency threshold of >2% and TDR mutations defined according to the 2009 WHO surveillance drug resistance mutations list. RESULTS: The majority (75.6%) were infected with subtype B and 6.6% with rare complex or unique recombinant forms. At a mutation frequency threshold of >20%, 7.2% (95% CI 5.0%-10.1%) of the sequences had TDR and this doubled to 15.8% (95% CI 12.6%-19.6%) at >2% mutation frequency (P < 0.0001). The majority (26/42, 62%) of low-frequency variants were against PIs. The most common mutations detected at >20% and 2%-20% mutation frequency differed for each drug class, these respectively being: L90M (n = 7) and M46IL (n = 10) for PIs; T215rev (n = 9) and D67GN (n = 4) for NRTIs; and K103N (n = 5) and G190E (n = 2) for NNRTIs. Combined TDR was more frequent in subtype B than non-B (OR = 0.38; 95% CI = 0.17-0.88; P = 0.024) and had minimal predicted effect on recommended first-line therapies. CONCLUSIONS: The data suggest differences in the types of low-frequency compared with majority TDR variants that require a better understanding of the origins and clinical significance of low-frequency variants. This will better inform diagnostic and treatment strategies.

Type: Article
Title: Enhanced surveillance of HIV-1 drug resistance in recently infected MSM in the UK
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/jac/dkw404
Publisher version: http://dx.doi.org/10.1093/jac/dkw404
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Polymerase chain reaction, mutation, drug resistance, HIV-1 surveillance, medical massively-parallel, genome sequencing, men who have sex with men
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute for Global Health > Infection and Population Health
URI: https://discovery.ucl.ac.uk/id/eprint/1524716
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