title: Treatment-naive individuals are the major source of transmitted HIV-1 drug resistance in men who have sex with men in the Swiss HIV Cohort Study.
abstract: BACKGROUND
  Human immunodeficiency virus type 1 (HIV-1) transmitted drug resistance (TDR) can compromise antiretroviral therapy (ART) and thus represents an important public health concern. Typically, sources of TDR remain unknown, but they can be characterized with molecular epidemiologic approaches. We used the highly representative Swiss HIV Cohort Study (SHCS) and linked drug resistance database (SHCS-DRDB) to analyze sources of TDR.
  
  
  METHODS
  ART-naive men who have sex with men with infection date estimates between 1996 and 2009 were chosen for surveillance of TDR in HIV-1 subtype B (N = 1674), as the SHCS-DRDB contains pre-ART genotypic resistance tests for >69% of this surveillance population. A phylogeny was inferred using pol sequences from surveillance patients and all subtype B sequences from the SHCS-DRDB (6934 additional patients). Potential sources of TDR were identified based on phylogenetic clustering, shared resistance mutations, genetic distance, and estimated infection dates.
  
  
  RESULTS
  One hundred forty of 1674 (8.4%) surveillance patients carried virus with TDR; 86 of 140 (61.4%) were assigned to clusters. Potential sources of TDR were found for 50 of 86 (58.1%) of these patients. ART-naive patients constitute 56 of 66 (84.8%) potential sources and were significantly overrepresented among sources (odds ratio, 6.43 [95% confidence interval, 3.22-12.82]; P < .001). Particularly large transmission clusters were observed for the L90M mutation, and the spread of L90M continued even after the near cessation of antiretroviral use selecting for that mutation. Three clusters showed evidence of reversion of K103N or T215Y/F.
  
  
  CONCLUSIONS
  Many individuals harboring viral TDR belonged to transmission clusters with other Swiss patients, indicating substantial domestic transmission of TDR in Switzerland. Most TDR in clusters could be linked to sources, indicating good surveillance of TDR in the SHCS-DRDB. Most TDR sources were ART naive. This, and the presence of long TDR transmission chains, suggests that resistance mutations are frequently transmitted among untreated individuals, highlighting the importance of early diagnosis and treatment.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Drescher
authors.forename: Viktor
authors.initials: V
authors.lastname: von Wyl
authors.forename: Wan-Lin
authors.initials: WL
authors.lastname: Yang
authors.forename: Jürg
authors.initials: J
authors.lastname: Böni
authors.forename: Sabine
authors.initials: S
authors.lastname: Yerly
authors.forename: Cyril
authors.initials: C
authors.lastname: Shah
authors.forename: Vincent
authors.initials: V
authors.lastname: Aubert
authors.forename: Thomas
authors.initials: T
authors.lastname: Klimkait
authors.forename: Patrick
authors.initials: P
authors.lastname: Taffé
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.forename: Juan
authors.initials: J
authors.lastname: Ambrosioni
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Pietro L
authors.initials: PL
authors.lastname: Vernazza
authors.forename: Bruno
authors.initials: B
authors.lastname: Ledergerber
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.forename: Roger D
authors.initials: RD
authors.lastname: Kouyos
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016000:Cluster Analysis; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D010802:Phylogeny; D017385:Sequence Homology; D013557:Switzerland / Q000453:epidemiology; D055815:Young Adult; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D054302:pol Gene Products, Human Immunodeficiency Virus
keywords: genotypic resistance testing; molecular epidemiology; transmitted antiretroviral drug resistance