title: Quantifying ongoing HIV-1 exposure in HIV-1-serodiscordant couples to identify individuals with potential host resistance to HIV-1.
abstract: BACKGROUND
  Immunogenetic correlates of resistance to HIV-1 in HIV-1-exposed seronegative (HESN) individuals with consistently high exposure may inform HIV-1 prevention strategies. We developed a novel approach for quantifying HIV-1 exposure to identify individuals remaining HIV-1 uninfected despite persistent high exposure.
  
  
  METHODS
  We used longitudinal predictors of HIV-1 transmission in HIV-1 serodiscordant couples to score HIV-1 exposure and define HESN clusters with persistently high, low, and decreasing risk trajectories. The model was validated in an independent cohort of serodiscordant couples. We describe a statistical tool that can be applied to other HESN cohorts to identify individuals with high exposure to HIV-1.
  
  
  RESULTS
  HIV-1 exposure was best quantified by frequency of unprotected sex with, plasma HIV-1 RNA levels among, and presence of genital ulcer disease among HIV-1-infected partners and by age, pregnancy status, herpes simplex virus 2 serostatus, and male circumcision status among HESN participants. Overall, 14% of HESN individuals persistently had high HIV-1 exposure and exhibited a declining incidence of HIV-1 infection over time.
  
  
  CONCLUSIONS
  A minority of HESN individuals from HIV-1-discordant couples had persistent high HIV-1 exposure over time. Decreasing incidence of infection in this group suggests these individuals were selected for resistance to HIV-1 and may be most appropriate for identifying biological correlates of natural host resistance to HIV-1 infection.
authors.affiliation: Department of Global Health, University of Washington, WA, USA. romelm@u.washington.edu
authors.forename: Romel D
authors.initials: RD
authors.lastname: Mackelprang
authors.forename: Jared M
authors.initials: JM
authors.lastname: Baeten
authors.forename: Deborah
authors.initials: D
authors.lastname: Donnell
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
authors.forename: Carey
authors.initials: C
authors.lastname: Farquhar
authors.forename: Guy
authors.initials: G
authors.lastname: de Bruyn
authors.forename: Max
authors.initials: M
authors.lastname: Essex
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.forename: Edith
authors.initials: E
authors.lastname: Nakku-Joloba
authors.forename: Jairam R
authors.initials: JR
authors.lastname: Lingappa
mesh_terms: D000328:Adult; D060467:Disease Resistance; D005191:Family Characteristics; D005260:Female; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology* / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification*; D006801:Humans; D015994:Incidence; D008297:Male; D015233:Models, Statistical; D011247:Pregnancy