title: Transmission networks of drug resistance acquired in primary/early stage HIV infection.
abstract: OBJECTIVE
  Population-based sequencing of primary/recent HIV infections (PHIs) can provide a framework for understanding transmission dynamics of local epidemics. In Quebec, half of PHIs represent clustered transmission events. This study ascertained the cumulative implications of clustering on onward transmission of drug resistance.
  
  
  METHODS
  HIV-1 pol sequence datasets were available for all genotyped PHI (<6 months postseroconversion; n = 848 subtype B infections, 1997-2007). Phylogenetic analysis established clustered transmission events, based on maximum likelihood topologies having high bootstrap values (>98%) and short genetic distances. The distributions of resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors and protease inhibitors in unique and clustered transmissions were ascertained.
  
  
  RESULTS
  Episodic clustering was observed in half of recent/early stage infections from 1997-2008. Overall, 29 and 28% of new infections segregated into small (<5 PHI/cluster, n = 242/848) and large transmission chains (> or =5 PHI/cluster, n = 239/848), averaging 2.8 +/- 0.1 and 10.3 +/- 1.0 PHI/cluster, respectively. The transmission of nucleoside analogue mutations and 215 resistant variants (T215C/D/I/F/N/S/Y) declined with clustering (7.9 vs. 3.4 vs. 1.2 and 5.8 vs. 1.7 vs. 1.1% for unique, small, and large clustered transmissions, respectively). In contrast, clustering was associated with the increased transmission of viruses harbouring resistance to nonnucleoside reverse transcriptase inhibitors (6.6 vs. 6.0 vs. 15.5%, respectively).
  
  
  CONCLUSIONS
  Clustering in early/PHI stage infection differentially affects transmission of drug resistance to different drug classes. Public health, prevention and diagnostic strategies, targeting PHI, afford a unique opportunity to curb the spread of transmitted drug resistance.
authors.affiliation: McGill University AIDS Centre, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Bluma G
authors.initials: BG
authors.lastname: Brenner
authors.forename: Michel
authors.initials: M
authors.lastname: Roger
authors.forename: Daniela D
authors.initials: DD
authors.lastname: Moisi
authors.forename: Maureen
authors.initials: M
authors.lastname: Oliveira
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hardy
authors.forename: Reuven
authors.initials: R
authors.lastname: Turgel
authors.forename: Hugues
authors.initials: H
authors.lastname: Charest
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wainberg
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D016000:Cluster Analysis; D004196:Disease Outbreaks / Q000517:prevention & control; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D011792:Quebec / Q000453:epidemiology; D012367:RNA, Viral / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D012307:Risk Factors; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors