title: Enhanced surveillance of HIV-1 drug resistance in recently infected MSM in the UK.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Virus Reference Department, National Infection Service, Public Health England, London, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Cunningham
authors.affiliation: Virus Reference Department, National Infection Service, Public Health England, London, UK.
authors.forename: Yuen-Ting
authors.initials: YT
authors.lastname: Chan
authors.affiliation: HIV and STI Department, National Infection Service, Public Health England, London, UK.
authors.forename: Adamma
authors.initials: A
authors.lastname: Aghaizu
authors.affiliation: Virus Reference Department, National Infection Service, Public Health England, London, UK.|National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Blood Borne and Sexually Transmitted Infections, University College London, London, UK.
authors.forename: David F
authors.initials: DF
authors.lastname: Bibby
authors.affiliation: Virus Reference Department, National Infection Service, Public Health England, London, UK.
authors.forename: Gary
authors.initials: G
authors.lastname: Murphy
authors.affiliation: Virus Reference Department, National Infection Service, Public Health England, London, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tosswill
authors.affiliation: Statistics, Modelling and Economics Department, National Infection Service, Public Health England, London, UK.
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Harris
authors.affiliation: Virus Reference Department, National Infection Service, Public Health England, London, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Myers
authors.affiliation: HIV and STI Department, National Infection Service, Public Health England, London, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Field
authors.affiliation: HIV and STI Department, National Infection Service, Public Health England, London, UK.|National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Blood Borne and Sexually Transmitted Infections, University College London, London, UK.
authors.forename: Valerie
authors.initials: V
authors.lastname: Delpech
authors.affiliation: Virus Reference Department, National Infection Service, Public Health England, London, UK.|National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Blood Borne and Sexually Transmitted Infections, University College London, London, UK.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Cane
authors.affiliation: HIV and STI Department, National Infection Service, Public Health England, London, UK.|National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Blood Borne and Sexually Transmitted Infections, University College London, London, UK.
authors.forename: O Noel
authors.initials: ON
authors.lastname: Gill
authors.affiliation: Virus Reference Department, National Infection Service, Public Health England, London, UK tamyo.mbisa@phe.gov.uk.|National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Blood Borne and Sexually Transmitted Infections, University College London, London, UK.
authors.forename: Jean L
authors.initials: JL
authors.lastname: Mbisa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D024882:Drug Resistance, Viral; D062665:Epidemiological Monitoring; D005838:Genotype; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D006113:United Kingdom; D055815:Young Adult; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D054302:pol Gene Products, Human Immunodeficiency Virus