title: Analysis of genetic linkage of HIV from couples enrolled in the HIV Prevention Trials Network 052 trial.
abstract: BACKGROUND
  The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early initiation of antiretroviral therapy (ART) reduces human immunodeficiency virus (HIV) transmission from HIV-infected adults (index participants) to their HIV-uninfected sexual partners. We analyzed HIV from 38 index-partner pairs and 80 unrelated index participants (controls) to assess the linkage of seroconversion events.
  
  
  METHODS
  Linkage was assessed using phylogenetic analysis of HIV pol sequences and Bayesian analysis of genetic distances between pol sequences from index-partner pairs and controls. Selected samples were also analyzed using next-generation sequencing (env region).
  
  
  RESULTS
  In 29 of the 38 (76.3%) cases analyzed, the index was the likely source of the partner's HIV infection (linked). In 7 cases (18.4%), the partner was most likely infected from a source other than the index participant (unlinked). In 2 cases (5.3%), linkage status could not be definitively established.
  
  
  CONCLUSIONS
  Nearly one-fifth of the seroconversion events in HPTN 052 were unlinked. The association of early ART and reduced HIV transmission was stronger when the analysis included only linked events. This underscores the importance of assessing the genetic linkage of HIV seroconversion events in HIV prevention studies involving serodiscordant couples.
authors: Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA. seshlem@jhmi.edu
authors: Susan H
authors: SH
authors: Eshleman
authors: Sarah E
authors: SE
authors: Hudelson
authors: Andrew D
authors: AD
authors: Redd
authors: Lei
authors: L
authors: Wang
authors: Rachel
authors: R
authors: Debes
authors: Ying Q
authors: YQ
authors: Chen
authors: Craig A
authors: CA
authors: Martens
authors: Stacy M
authors: SM
authors: Ricklefs
authors: Ethan J
authors: EJ
authors: Selig
authors: Stephen F
authors: SF
authors: Porcella
authors: Supriya
authors: S
authors: Munshaw
authors: Stuart C
authors: SC
authors: Ray
authors: Estelle
authors: E
authors: Piwowar-Manning
authors: Marybeth
authors: M
authors: McCauley
authors: Mina C
authors: MC
authors: Hosseinipour
authors: Johnstone
authors: J
authors: Kumwenda
authors: James G
authors: JG
authors: Hakim
authors: Suwat
authors: S
authors: Chariyalertsak
authors: Guy
authors: G
authors: de Bruyn
authors: Beatriz
authors: B
authors: Grinsztejn
authors: Nagalingeswaran
authors: N
authors: Kumarasamy
authors: Joseph
authors: J
authors: Makhema
authors: Kenneth H
authors: KH
authors: Mayer
authors: Jose
authors: J
authors: Pilotto
authors: Breno R
authors: BR
authors: Santos
authors: Thomas C
authors: TC
authors: Quinn
authors: Myron S
authors: MS
authors: Cohen
authors: James P
authors: JP
authors: Hughes
mesh_terms: D000328:Adult; D001499:Bayes Theorem; D005260:Female; D008040:Genetic Linkage; D006679:HIV Seropositivity / Q000235:genetics* / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008297:Male; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D012747:Sexual Partners; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D054302:pol Gene Products, Human Immunodeficiency Virus