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.
Bibliographical noteFunding Information:
We thank Kieren Lythgow for additional bioinformatics support. We also wish to thank Samuel Moses, Gkikas Magiorkinis and the NIHR HPRU in Blood Borne and Sexually Transmitted Infections Steering Committee: Caroline Sabin (Director), Anthony Nardone (PHE Lead), Catherine Mercer, Gwenda Hughes, Jackie Cassell, Greta Rait, Samreen Ijaz, Tim Rhodes, Kholoud Porter and William Rosenberg. This research was funded by Public Health England (PHE) and by the National Institute for Health Research and undertaken by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Blood Borne and Sexually Transmitted Infections at UCL in partnership with PHE and in collaboration with the London School of Hygiene and Tropical Medicine.
© The Author 2016.
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