title: The impact of transmission clusters on primary drug resistance in newly diagnosed HIV-1 infection.
abstract: OBJECTIVE
  To monitor HIV-1 transmitted drug resistance (TDR) in a well defined urban area with large access to antiretroviral therapy and to assess the potential source of infection of newly diagnosed HIV individuals.
  
  
  METHODS
  All individuals resident in Geneva, Switzerland, with a newly diagnosed HIV infection between 2000 and 2008 were screened for HIV resistance. An infection was considered as recent when the positive test followed a negative screening test within less than 1 year. Phylogenetic analyses were performed by using the maximum likelihood method on pol sequences including 1058 individuals with chronic infection living in Geneva.
  
  
  RESULTS
  Of 637 individuals with newly diagnosed HIV infection, 20% had a recent infection. Mutations associated with resistance to at least one drug class were detected in 8.5% [nucleoside reverse transcriptase inhibitors (NRTIs), 6.3%; non-nucleoside reverse transcriptase inhibitors (NNRTIs), 3.5%; protease inhibitors, 1.9%]. TDR (P-trend = 0.015) and, in particular, NNRTI resistance (P = 0.002) increased from 2000 to 2008. Phylogenetic analyses revealed that 34.9% of newly diagnosed individuals, and 52.7% of those with recent infection were linked to transmission clusters. Clusters were more frequent in individuals with TDR than in those with sensitive strains (59.3 vs. 32.6%, respectively; P < 0.0001). Moreover, 84% of newly diagnosed individuals with TDR were part of clusters composed of only newly diagnosed individuals.
  
  
  CONCLUSIONS
  Reconstruction of the HIV transmission networks using phylogenetic analysis shows that newly diagnosed HIV infections are a significant source of onward transmission, particularly of resistant strains, thus suggesting an important self-fueling mechanism for TDR.
authors.affiliation: University of Geneva Medical School, Geneva's University Hospitals, Switzerland. sabine.yerly@hcuge.ch
authors.forename: Sabine
authors.initials: S
authors.lastname: Yerly
authors.forename: Thomas
authors.initials: T
authors.lastname: Junier
authors.forename: Angèle
authors.initials: A
authors.lastname: Gayet-Ageron
authors.forename: Emmanuelle Boffi El
authors.initials: EB
authors.lastname: Amari
authors.forename: Viktor
authors.initials: V
authors.lastname: von Wyl
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.forename: Bernard
authors.initials: B
authors.lastname: Hirschel
authors.forename: Evgeny
authors.initials: E
authors.lastname: Zdobnov
authors.forename: Laurent
authors.initials: L
authors.lastname: Kaiser
mesh_terms: D000328:Adult; D024882:Drug Resistance, Viral / Q000235:genetics*; D004812:Epidemiologic Methods; D005260:Female; D015658:HIV Infections / Q000235:genetics / Q000635:transmission* / Q000821:virology; D015497:HIV-1; D006801:Humans; D008297:Male; D010802:Phylogeny