title: Design of epidemiological studies measuring genital and plasma HIV-1 outcomes: lessons from a randomised controlled trial.
abstract: OBJECTIVE
  HIV-1 genital viral loads have not been extensively used as markers of HIV transmissibility. We set out to determine whether the variability of genital HIV-1 RNA over time necessitates design adjustments in studies measuring genital shedding to account for this variability.
  
  
  METHODS
  We used data from a completed trial of HSV suppressive therapy to estimate the correlation of plasma and genital HIV-1 RNA quantities sampled at different times. These correlation estimates were used to estimate the relative sample sizes needed to detect an impact on HIV-1 genital and plasma quantities assuming a variable number of pre- and post-randomisation repeated measurements. The treatment effect on quantities of genital and plasma HIV-1 RNA were analysed using random effects linear regression.
  
  
  RESULTS
  Post-randomisation plasma HIV-1 RNA was highly correlated within-women, while genital HIV-1 RNA was less strongly correlated. Related to this, the sample size required to detect a treatment effect on genital HIV-1 RNA decreased with increasing numbers of post-randomisation measurements up to 6-7 measurements, but varied less for plasma HIV-1 RNA. In contrast, repeated pre-randomisation measurements of plasma HIV-1 RNA increased study power more than genital HIV-1 RNA because of the high correlation of plasma HIV-1 RNA measurements between the pre- and post-randomisation samples. Re-analysis of the trial data illustrated the increased precision of the treatment effect on genital HIV-1 with increasing post-randomisation measurements.
  
  
  CONCLUSIONS
  Designs allowing for repeated post-randomisation measures should be used to increase the precision in estimates of genital HIV-1 RNA. Repeated post-randomisation measurements of plasma HIV-1 RNA are of limited benefit.
authors.affiliation: Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, UK. natasha.larke@lshtm.ac.uk
authors.forename: Natasha L
authors.initials: NL
authors.lastname: Larke
authors.forename: Helen A
authors.initials: HA
authors.lastname: Weiss
authors.forename: Philippe
authors.initials: P
authors.lastname: Mayaud
authors.forename: Philippe
authors.initials: P
authors.lastname: Van de Perre
authors.forename: Tim
authors.initials: T
authors.lastname: Clayton
authors.forename: Abdoulaye
authors.initials: A
authors.lastname: Ouedraogo
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nagot
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D004812:Epidemiologic Methods; D005260:Female; D005836:Genitalia, Female / Q000821:virology*; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006558:Herpes Genitalis / Q000150:complications / Q000188:drug therapy; D006801:Humans; D012367:RNA, Viral / Q000032:analysis / Q000097:blood; D012107:Research Design; D016896:Treatment Outcome; D019562:Viral Load; D017201:Virus Shedding
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral