title: Using plasma viral load to guide antiretroviral therapy initiation to prevent HIV-1 transmission.
abstract: BACKGROUND
  Current WHO guidelines recommend antiretroviral therapy (ART) initiation at CD4 counts ≤350 cells/µL. Increasing this threshold has been proposed, with a primary goal of reducing HIV-1 infectiousness. Because the quantity of HIV-1 in plasma is the primary predictor of HIV-1 transmission, consideration of plasma viral load in ART initiation guidelines is warranted.
  
  
  METHODS
  Using per-sex-act infectivity estimates and cross-sectional sexual behavior data from 2,484 HIV-1 infected persons with CD4 counts >350 enrolled in a study of African heterosexual HIV-1 serodiscordant couples, we calculated the number of transmissions expected and the number potentially averted under selected scenarios for ART initiation: i) CD4 count <500 cells/µL, ii) viral load ≥10,000 or ≥50,000 copies/mL and iii) universal treatment. For each scenario, we estimated the proportion of expected infections that could be averted, the proportion of infected persons initiating treatment, and the ratio of these proportions.
  
  
  RESULTS
  Initiating treatment at viral load ≥50,000 copies/mL would require treating 19.8% of infected persons with CD4 counts >350 while averting 40.5% of expected transmissions (ratio 2.0); treating at viral load ≥10,0000 copies/mL had a ratio of 1.5. In contrast, initiation at CD4 count <500 would require treating 41.8%, while averting 48.4% (ratio 1.1).
  
  
  CONCLUSIONS
  Inclusion of viral load in ART initiation guidelines could permit targeting ART resources to HIV-1 infected persons who have a higher risk of transmitting HIV-1. Further work is needed to estimate costs and feasibility.
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, Washington, United States of America. pmurnane@uw.edu
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Murnane
authors.forename: James P
authors.initials: JP
authors.lastname: Hughes
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
authors.forename: Jairam R
authors.initials: JR
authors.lastname: Lingappa
authors.forename: Nelly
authors.initials: N
authors.lastname: Mugo
authors.forename: Carey
authors.initials: C
authors.lastname: Farquhar
authors.forename: James
authors.initials: J
authors.lastname: Kiarie
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
authors.forename: Jared M
authors.initials: JM
authors.lastname: Baeten
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000517:prevention & control / Q000635:transmission* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008297:Male; D017410:Practice Guidelines as Topic; D012725:Sexual Behavior / Q000706:statistics & numerical data; D019562:Viral Load / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents