title: A cluster of human immunodeficiency virus Type 1 recombinant form escaping detection by commercial genomic amplification assays.
abstract: BACKGROUND
  Nucleic acid testing (NAT)-based methods for the detection and quantification of human immunodeficiency virus Type 1 (HIV-1) RNA are used to increase transfusion safety and to diagnose and manage HIV-1-infected patients. We describe a novel HIV-1 recombinant form associated with lack of reactivity or substantial underestimation of viral load by commercial NAT assays.
  
  
  METHODS
  We observed a repeat blood donor seroconverting to anti-HIV in whom HIV RNA was initially undetectable with routine NAT was observed. During donor follow-up, HIV RNA became detectable, but the viral load was 2 to 3 log lower than measured with other NATs targeting different genome regions. Genome sequencing revealed a novel B/F recombinant with mutations affecting primers and probe annealing accounting for the poor performance of routine NAT. A total of 553 HIV-1-infected patients attending the hospital clinic were subsequently tested prospectively using the routine assay and an in-house assay specifically designed to detect the B/F strains.
  
  
  RESULTS
  The routine assay substantially underestimated viremia (1-5 log) in 19 cases (3.5%), 11 (58%) of which were infected with the same B/F strain observed in the index donor samples. Two other non-B circulating recombinant forms of HIV-1 (A/G, B/G subtypes) were identified as poorly detected. Newly introduced NATs targeting two HIV-1 regions improved assay performance.
  
  
  CONCLUSIONS
  HIV-1 increasing heterogeneity affects the efficiency of NATs and consequently the safety of the blood supply as well as diagnosis and patient management.
authors.affiliation: Department of Transfusion Medicine and Hematology and Infectious Diseases Unit, Ospedale A. Manzoni, Lecco, Italy. b.foglieni@ospedale.lecco.it
authors.forename: Barbara
authors.initials: B
authors.lastname: Foglieni
authors.forename: Daniel
authors.initials: D
authors.lastname: Candotti
authors.forename: Irene
authors.initials: I
authors.lastname: Guarnori
authors.forename: Livia
authors.initials: L
authors.lastname: Raffaele
authors.forename: Alessandra
authors.initials: A
authors.lastname: Berzuini
authors.forename: Marta
authors.initials: M
authors.lastname: Spreafico
authors.forename: Anna
authors.initials: A
authors.lastname: Orani
authors.forename: Roberto
authors.initials: R
authors.lastname: Rossotti
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Allain
authors.forename: Daniele
authors.initials: D
authors.lastname: Prati
mesh_terms: D001782:Blood Donors; D046148:Donor Selection / Q000379:methods; D015658:HIV Infections / Q000097:blood; D006679:HIV Seropositivity; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics; D014766:Viremia / Q000821:virology
chemical_list: D012367:RNA, Viral