title: HIV-1 Transmission During Recent Infection and During Treatment Interruptions as Major Drivers of New Infections in the Swiss HIV Cohort Study.
abstract: BACKGROUND
  Reducing the fraction of transmissions during recent human immunodeficiency virus (HIV) infection is essential for the population-level success of "treatment as prevention".
  
  
  METHODS
  A phylogenetic tree was constructed with 19 604 Swiss sequences and 90 994 non-Swiss background sequences. Swiss transmission pairs were identified using 104 combinations of genetic distance (1%-2.5%) and bootstrap (50%-100%) thresholds, to examine the effect of those criteria. Monophyletic pairs were classified as recent or chronic transmission based on the time interval between estimated seroconversion dates. Logistic regression with adjustment for clinical and demographic characteristics was used to identify risk factors associated with transmission during recent or chronic infection.
  
  
  RESULTS
  Seroconversion dates were estimated for 4079 patients on the phylogeny, and comprised between 71 (distance, 1%; bootstrap, 100%) to 378 transmission pairs (distance, 2.5%; bootstrap, 50%). We found that 43.7% (range, 41%-56%) of the transmissions occurred during the first year of infection. Stricter phylogenetic definition of transmission pairs was associated with higher recent-phase transmission fraction. Chronic-phase viral load area under the curve (adjusted odds ratio, 3; 95% confidence interval, 1.64-5.48) and time to antiretroviral therapy (ART) start (adjusted odds ratio 1.4/y; 1.11-1.77) were associated with chronic-phase transmission as opposed to recent transmission. Importantly, at least 14% of the chronic-phase transmission events occurred after the transmitter had interrupted ART.
  
  
  CONCLUSIONS
  We demonstrate a high fraction of transmission during recent HIV infection but also chronic transmissions after interruption of ART in Switzerland. Both represent key issues for treatment as prevention and underline the importance of early diagnosis and of early and continuous treatment.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich.|Institute of Medical Virology, University of Zurich.
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authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich.|Institute of Medical Virology, University of Zurich.
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authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich.|Institute of Medical Virology, University of Zurich.
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authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich.|Institute of Medical Virology, University of Zurich.
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authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich.|Institute of Medical Virology, University of Zurich.
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authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich.|Institute of Medical Virology, University of Zurich.
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mesh_terms: D000328:Adult; D000465:Algorithms; D016000:Cluster Analysis; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008297:Male; D010802:Phylogeny; D012307:Risk Factors; D013557:Switzerland / Q000453:epidemiology
keywords: HIV recent (early) infection; HIV transmission; endgame; treatment as prevention; treatment interruptions