title: Associations between phylogenetic clustering and HLA profile among HIV-infected individuals in San Diego, California.
abstract: BACKGROUND
  Specific sequence changes of human immunodeficiency virus type 1 (HIV-1) in the presence of specific HLA molecules may alter the composition and processing of viral peptides, leading to immune escape. Persistence of these mutations after transmission may leave the genetic fingerprint of the transmitter's HLA profile. Here, we evaluated the associations between HLA profiles and the phylogenetic relationships of HIV sequences sampled from a cohort of recently infected individuals in San Diego, California.
  
  
  METHODS
  We identified transmission clusters within the study cohort, using phylogenetic analysis of sampled HIV pol genotypes at a genetic distance of <1.5%. We then evaluated the association of specific HLA alleles, HLA homozygosity, HLA concordance, race and ethnicity, and mutational patterns within the clustering and nonclustering groups.
  
  
  RESULTS
  From 350 cohort participants, we identified 162 clustering individuals and 188 nonclustering individuals. We identified trends for enrichment of particular alleles within individual clusters and evidence of viral escape within those clusters. We also found that discordance of HLA alleles was significantly associated with clustering individuals.
  
  
  CONCLUSIONS
  Some transmission clusters demonstrate HLA enrichment, and viruses in these HLA-associated clusters often show evidence of escape to enriched alleles. Interestingly, HLA discordance was associated with clustering in our predominantly MSM population.
authors.affiliation: Department of Medicine, University of California, San Diego, CA 92093-0711, USA. srmehta@ucsd.edu
authors.forename: Sanjay R
authors.initials: SR
authors.lastname: Mehta
authors.forename: Sergei L
authors.initials: SL
authors.lastname: Kosakovsky Pond
authors.forename: Jason A
authors.initials: JA
authors.lastname: Young
authors.forename: Douglas
authors.initials: D
authors.lastname: Richman
authors.forename: Susan
authors.initials: S
authors.lastname: Little
authors.forename: Davey M
authors.initials: DM
authors.lastname: Smith
mesh_terms: D000483:Alleles; D002140:California; D016000:Cluster Analysis; D015331:Cohort Studies; D003710:Demography; D005260:Female; D015751:Genes, pol / Q000235:genetics*; D015658:HIV Infections / Q000276:immunology / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D015234:HLA-A Antigens / Q000235:genetics* / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology; D018451:Homosexuality, Male; D006720:Homozygote; D006801:Humans; D057131:Immune Evasion; D008297:Male; D009154:Mutation; D010802:Phylogeny; D012307:Risk Factors
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens