A cluster of human immunodeficiency virus Type 1 recombinant form escaping detection by commercial genomic amplification assays

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...

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Bibliographic Details
Published in:Transfusion (Philadelphia, Pa.) Pa.), 2011-04, Vol.51 (4), p.719-730
Main Authors: Foglieni, Barbara, Candotti, Daniel, Guarnori, Irene, Raffaele, Livia, Berzuini, Alessandra, Spreafico, Marta, Orani, Anna, Rossotti, Roberto, Rossi, Davide, Allain, Jean-Pierre, Prati, Daniele
Format: Article
Language:English
Subjects:
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Assays
Biological and medical sciences
Blood Donors
Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis
DNA probes
Donor Selection - methods
Genomes
genomics
HIV Infections - blood
HIV Seropositivity
HIV-1 - genetics
HIV-1 - isolation & purification
Hospitals
Human immunodeficiency virus
Human immunodeficiency virus 1
Human viral diseases
Humans
Infectious diseases
Medical sciences
Mutation
nucleic acids
Phylogeny
Polymerase Chain Reaction
Primers
RNA
RNA, Viral - genetics
Transfusion
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
Viral diseases
Viral hepatitis
Viremia
Viremia - virology
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Summary: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. STUDY DESIGN AND 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. CONCLUSION: HIV‐1 increasing heterogeneity affects the efficiency of NATs and consequently the safety of the blood supply as well as diagnosis and patient management.
ISSN:0041-1132
1537-2995
DOI:10.1111/j.1537-2995.2010.02942.x