title: The role of viral introductions in sustaining community-based HIV epidemics in rural Uganda: evidence from spatial clustering, phylogenetics, and egocentric transmission models.
abstract: BACKGROUND
  It is often assumed that local sexual networks play a dominant role in HIV spread in sub-Saharan Africa. The aim of this study was to determine the extent to which continued HIV transmission in rural communities--home to two-thirds of the African population--is driven by intra-community sexual networks versus viral introductions from outside of communities.
  
  
  RESULTS
  We analyzed the spatial dynamics of HIV transmission in rural Rakai District, Uganda, using data from a cohort of 14,594 individuals within 46 communities. We applied spatial clustering statistics, viral phylogenetics, and probabilistic transmission models to quantify the relative contribution of viral introductions into communities versus community- and household-based transmission to HIV incidence. Individuals living in households with HIV-incident (n = 189) or HIV-prevalent (n = 1,597) persons were 3.2 (95% CI: 2.7-3.7) times more likely to be HIV infected themselves compared to the population in general, but spatial clustering outside of households was relatively weak and was confined to distances <500 m. Phylogenetic analyses of gag and env genes suggest that chains of transmission frequently cross community boundaries. A total of 95 phylogenetic clusters were identified, of which 44% (42/95) were two individuals sharing a household. Among the remaining clusters, 72% (38/53) crossed community boundaries. Using the locations of self-reported sexual partners, we estimate that 39% (95% CI: 34%-42%) of new viral transmissions occur within stable household partnerships, and that among those infected by extra-household sexual partners, 62% (95% CI: 55%-70%) are infected by sexual partners from outside their community. These results rely on the representativeness of the sample and the quality of self-reported partnership data and may not reflect HIV transmission patterns outside of Rakai.
  
  
  CONCLUSIONS
  Our findings suggest that HIV introductions into communities are common and account for a significant proportion of new HIV infections acquired outside of households in rural Uganda, though the extent to which this is true elsewhere in Africa remains unknown. Our results also suggest that HIV prevention efforts should be implemented at spatial scales broader than the community and should target key populations likely responsible for introductions into communities.
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Grabowski
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Justin
authors.initials: J
authors.lastname: Lessler
authors.affiliation: Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Redd
authors.affiliation: Rakai Health Sciences Program, Kalisizo, Uganda.
authors.forename: Joseph
authors.initials: J
authors.lastname: Kagaayi
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America; Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America; School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Oliver
authors.initials: O
authors.lastname: Laeyendecker
authors.affiliation: Rakai Health Sciences Program, Kalisizo, Uganda.
authors.forename: Anthony
authors.initials: A
authors.lastname: Ndyanabo
authors.affiliation: Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Martha I
authors.initials: MI
authors.lastname: Nelson
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Derek A T
authors.initials: DA
authors.lastname: Cummings
authors.affiliation: Rakai Health Sciences Program, Kalisizo, Uganda.
authors.forename: John Baptiste
authors.initials: JB
authors.lastname: Bwanika
authors.affiliation: School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Mueller
authors.affiliation: Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America; Rakai Health Sciences Program, Kalisizo, Uganda; School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Reynolds
authors.affiliation: School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Supriya
authors.initials: S
authors.lastname: Munshaw
authors.affiliation: School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Ray
authors.affiliation: Rakai Health Sciences Program, Kalisizo, Uganda.
authors.forename: Tom
authors.initials: T
authors.lastname: Lutalo
authors.affiliation: School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Jordyn
authors.initials: J
authors.lastname: Manucci
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America; Rakai Health Sciences Program, Kalisizo, Uganda; School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Aaron A R
authors.initials: AA
authors.lastname: Tobian
authors.affiliation: Rakai Health Sciences Program, Kalisizo, Uganda; School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Larry W
authors.initials: LW
authors.lastname: Chang
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Chris
authors.initials: C
authors.lastname: Beyrer
authors.affiliation: School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Jacky M
authors.initials: JM
authors.lastname: Jennings
authors.affiliation: Rakai Health Sciences Program, Kalisizo, Uganda.
authors.forename: Fred
authors.initials: F
authors.lastname: Nalugoda
authors.affiliation: Rakai Health Sciences Program, Kalisizo, Uganda; School of Public Health, College of Medicine, Makerere University, Kampala, Uganda.
authors.forename: David
authors.initials: D
authors.lastname: Serwadda
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America; Rakai Health Sciences Program, Kalisizo, Uganda.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Wawer
authors.affiliation: Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America; School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America; Rakai Health Sciences Program, Kalisizo, Uganda.
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Gray
mesh_terms: D000293:Adolescent; D000328:Adult; D058872:Epidemics; D005260:Female; D015658:HIV Infections / Q000453:epidemiology* / Q000635:transmission* / Q000821:virology; D006679:HIV Seropositivity / Q000453:epidemiology / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D010802:Phylogeny; D015995:Prevalence; D012424:Rural Population; D012725:Sexual Behavior; D014454:Uganda / Q000453:epidemiology; D055815:Young Adult