title: Estimating the impact of plasma HIV-1 RNA reductions on heterosexual HIV-1 transmission risk.
abstract: BACKGROUND
  The risk of sexual transmission of HIV-1 is strongly associated with the level of HIV-1 RNA in plasma making reduction in HIV-1 plasma levels an important target for HIV-1 prevention interventions. A quantitative understanding of the relationship of plasma HIV-1 RNA and HIV-1 transmission risk could help predict the impact of candidate HIV-1 prevention interventions that operate by reducing plasma HIV-1 levels, such as antiretroviral therapy (ART), therapeutic vaccines, and other non-ART interventions.
  
  
  RESULTS
  We use prospective data collected from 2004 to 2008 in East and Southern African HIV-1 serodiscordant couples to model the relationship of plasma HIV-1 RNA levels and heterosexual transmission risk with confirmation of HIV-1 transmission events by HIV-1 sequencing. The model is based on follow-up of 3381 HIV-1 serodiscordant couples over 5017 person-years encompassing 108 genetically-linked HIV-1 transmission events. HIV-1 transmission risk was 2.27 per 100 person-years with a log-linear relationship to log(10) plasma HIV-1 RNA. The model predicts that a decrease in average plasma HIV-1 RNA of 0.74 log(10) copies/mL (95% CI 0.60 to 0.97) reduces heterosexual transmission risk by 50%, regardless of the average starting plasma HIV-1 level in the population and independent of other HIV-1-related population characteristics. In a simulated population with a similar plasma HIV-1 RNA distribution the model estimates that 90% of overall HIV-1 infections averted by a 0.74 copies/mL reduction in plasma HIV-1 RNA could be achieved by targeting this reduction to the 58% of the cohort with plasma HIV-1 levels ≥4 log(10) copies/mL.
  
  
  CONCLUSIONS
  This log-linear model of plasma HIV-1 levels and risk of sexual HIV-1 transmission may help estimate the impact on HIV-1 transmission and infections averted from candidate interventions that reduce plasma HIV-1 RNA levels.
authors.affiliation: Department of Global Health, University of Washington, Seattle, Washington, United States of America. lingappa@uw.edu
authors.forename: Jairam R
authors.initials: JR
authors.lastname: Lingappa
authors.forename: James P
authors.initials: JP
authors.lastname: Hughes
authors.forename: Richard S
authors.initials: RS
authors.lastname: Wang
authors.forename: Jared M
authors.initials: JM
authors.lastname: Baeten
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
authors.forename: Glenda E
authors.initials: GE
authors.lastname: Gray
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Stevens
authors.forename: Deborah
authors.initials: D
authors.lastname: Donnell
authors.forename: Mary S
authors.initials: MS
authors.lastname: Campbell
authors.forename: Carey
authors.initials: C
authors.lastname: Farquhar
authors.forename: M
authors.initials: M
authors.lastname: Essex
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
authors.forename: Robert W
authors.initials: RW
authors.lastname: Coombs
authors.forename: Helen
authors.initials: H
authors.lastname: Rees
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
mesh_terms: D000351:Africa, Eastern; D000353:Africa, Southern; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control* / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D020010:Heterosexuality; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood* / Q000235:genetics; D012307:Risk Factors; D012747:Sexual Partners; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral