title: Phylogenetic relatedness of circulating HIV-1C variants in Mochudi, Botswana.
abstract: BACKGROUND
  Determining patterns of HIV transmission is increasingly important for the most efficient use of modern prevention interventions. HIV phylogeny can provide a better understanding of the mechanisms underlying HIV transmission networks in communities.
  
  
  METHODS
  To reconstruct the structure and dynamics of a local HIV/AIDS epidemic, the phylogenetic relatedness of HIV-1 subtype C env sequences obtained from 785 HIV-infected community residents in the northeastern sector of Mochudi, Botswana, during 2010-2013 was estimated. The genotyping coverage was estimated at 44%. Clusters were defined based on relatedness of HIV-1C env sequences and bootstrap support of splits.
  
  
  RESULTS
  The overall proportion of clustered HIV-1C env sequences was 19.1% (95% CI 17.5% to 20.8%). The proportion of clustered sequences from Mochudi was significantly higher than the proportion of non-Mochudi sequences that clustered, 27.0% vs. 14.7% (p = 5.8E-12; Fisher exact test). The majority of clustered Mochudi sequences (90.1%; 95% CI 85.1% to 93.6%) were found in the Mochudi-unique clusters. None of the sequences from Mochudi clustered with any of the 1,244 non-Botswana HIV-1C sequences. At least 83 distinct HIV-1C variants, or chains of HIV transmission, in Mochudi were enumerated, and their sequence signatures were reconstructed. Seven of 20 genotyped seroconverters were found in 7 distinct clusters.
  
  
  CONCLUSIONS
  The study provides essential characteristics of the HIV transmission network in a community in Botswana, suggests the importance of high sampling coverage, and highlights the need for broad HIV genotyping to determine the spread of community-unique and community-mixed viral variants circulating in local epidemics. The proposed methodology of cluster analysis enumerates circulating HIV variants and can work well for surveillance of HIV transmission networks. HIV genotyping at the community level can help to optimize and balance HIV prevention strategies in trials and combined intervention packages.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Novitsky
authors.affiliation: Botswana-Harvard AIDS Institute Partnership, Gaborone, Botswana.
authors.forename: Hermann
authors.initials: H
authors.lastname: Bussmann
authors.affiliation: Botswana-Harvard AIDS Institute Partnership, Gaborone, Botswana.
authors.forename: Andrew
authors.initials: A
authors.lastname: Logan
authors.affiliation: Botswana-Harvard AIDS Institute Partnership, Gaborone, Botswana.
authors.forename: Sikhulile
authors.initials: S
authors.lastname: Moyo
authors.affiliation: Botswana-Harvard AIDS Institute Partnership, Gaborone, Botswana.
authors.forename: Erik
authors.initials: E
authors.lastname: van Widenfelt
authors.affiliation: Botswana-Harvard AIDS Institute Partnership, Gaborone, Botswana.
authors.forename: Lillian
authors.initials: L
authors.lastname: Okui
authors.affiliation: Botswana-Harvard AIDS Institute Partnership, Gaborone, Botswana.
authors.forename: Mompati
authors.initials: M
authors.lastname: Mmalane
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Jeannie
authors.initials: J
authors.lastname: Baca
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Lauren
authors.initials: L
authors.lastname: Buck
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Phillips
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Tim
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Mary Fran
authors.initials: MF
authors.lastname: McLane
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Quanhong
authors.initials: Q
authors.lastname: Lei
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Botswana-Harvard AIDS Institute Partnership, Gaborone, Botswana.
authors.forename: Joseph
authors.initials: J
authors.lastname: Makhema
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Shahin
authors.initials: S
authors.lastname: Lockman
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Victor
authors.initials: V
authors.lastname: DeGruttola
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: M
authors.initials: M
authors.lastname: Essex
mesh_terms: D001902:Botswana; D015752:Genes, env / Q000235:genetics; D005838:Genotype; D015658:HIV Infections / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D010802:Phylogeny