title: Evidence of Self-Sustaining Drug Resistant HIV-1 Lineages Among Untreated Patients in the United Kingdom.
abstract: BACKGROUND
  About 10% of new diagnoses of subtype B human immunodeficiency virus type 1 (HIV-1) in the United Kingdom are with viruses showing transmitted drug resistance (TDR). However, there is discordance between the mutation patterns observed in HIV-infected patients failing therapy and those seen in TDR.
  
  
  METHODS
  We extracted all subtype B HIV-1 pol gene sequences from treatment-naive patients within the United Kingdom HIV Drug Resistance Database sampled between 1997 and 2011 and carrying the most common protease inhibitors, nonnucleoside and nucleotide reverse transcriptase inhibitors TDR mutations, namely, L90M, K103N, and T215Y/F/rev, respectively (n = 1140). Transmission clusters (n ≥ 2 sequences) were identified by maximum-likelihood phylogeny using a genetic distance cutoff of ≤ 1.5%. The time of origin and the basic reproductive number (R0) of clusters were estimated by Bayesian methods.
  
  
  RESULTS
  T215rev was present alone in 47% of the sequences (n = 540), K103N in 31% (n = 359), and L90M in 10% (n = 109). The remaining sequences contained T215Y or combinations of L90M, K103N, and T215rev. Fifty-five percent (n = 624) of the sequences formed highly supported transmission clusters (n = 193) containing between 2 and 15 sequences. The time of origin of 10 large clusters (≥ 8 sequences) was estimated to be between 2000 (1999-2002; 95% highest posterior density [HPD]) and 2006 (2005-2007; 95% HPD). The oldest cluster had persisted for nearly 8 years. All 10 clusters had R0s ranging from 1.3 (0.4-2.5; 95% HPD) to 2.8 (0.6-6.5; 95% HPD).
  
  
  CONCLUSIONS
  A high proportion of the most common TDR in subtype B infections in the United Kingdom is derived by onward transmission from treatment-naive patients.
authors.affiliation: Antiviral Unit, Virus Reference Department, Public Health England.
authors.forename: Jean L
authors.initials: JL
authors.lastname: Mbisa
authors.affiliation: Medical Research Council Clinical Trials Unit.
authors.forename: Esther
authors.initials: E
authors.lastname: Fearnhill
authors.affiliation: Medical Research Council Clinical Trials Unit.
authors.forename: David T
authors.initials: DT
authors.lastname: Dunn
authors.affiliation: Research Department of Infection, University College London.
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
authors.affiliation: Chelsea and Westminster Hospital, London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Asboe
authors.affiliation: Antiviral Unit, Virus Reference Department, Public Health England.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Cane
mesh_terms: D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000453:epidemiology* / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics*; D006801:Humans; D008297:Male; D015233:Models, Statistical; D010802:Phylogeny; D006113:United Kingdom / Q000453:epidemiology
keywords: HIV-1–transmitted drug resistance; subtype B; treatment-naive patients