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

Foglieni, Barbara; Candotti, Daniel; Guarnori, I.; Raffaele, L.; Berzuini, Alessandra; Spreafico, M.; Orani, Anna Maria; Rossotti, Roberto; Rossi, Davide; Allain, Jean‐Pierre; Prati, Daniele

doi:10.1111/j.1537-2995.2010.02942.x

Cited by 32 publications

(39 citation statements)

References 28 publications

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“…anti-HIV1/2 positive, screening NAT negative. A related publication describes false-negative or underquantified results with the mono-target assays COBAS AmpliScreen HIV-1 Test v1.5 and COBAS Amplicor HIV-1 Monitor Test v1.5 with viral variants circulating in Italy [10]. Another publication from Germany described new genetic polymorphisms in the LTR region affecting an in-house developed real-time PCR blood-screening test [9].…”

Section: Discussionmentioning

confidence: 99%

“…The cases were traceable to false-negative test results in the routine NAT assays due to new variants of the common HIV-1 subtype B missed by the assays' design. Recently, details of these 2 transmission cases and a number of related cases of false-negative HIV-1 NAT screening results have been published [8,9,10,11,12]. In addition, we must emphasize that cases of false-negative HIV-1 NAT based on low viral load combined with suboptimal NAT sensitivity in the screening of mini pools cannot be excluded.…”

Section: Introductionmentioning

confidence: 99%

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Risk Minimization Measures for Blood Screening HIV-1 Nucleic Acid Amplification Technique Assays in Germany

Chudy

Kreß

Halbauer

et al. 2013

Transfus Med Hemother

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Background: Several publications describe HIV-1 RNA false-negative results or viral load underquantitation associated with Communauté Européenne(CE)-marked qualitative or quantitative nucleic acid amplification technique (NAT) assays. 6 cases occurred during blood screening in Germany, with 2 of them causing HIV-1 transmissions to recipients of blood components. The implicated NAT assays were mono-target assays amplifying in different viral genome regions (gag or long terminal repeat). Methods: Specimens characterized by HIV-1 NAT underquantitation or false-negative NAT results were comparatively investigated in CE-marked HIV-1 NAT systems of different design to identify potential reasons. The target regions of the viral nucleic acids were sequenced and these sequences compared to primers and probes of the assays. Potential risk minimization measures were considered for quantitative and blood-screening HIV-1 NAT systems. Results: Nucleotide sequencing of the viral target region in cases of HIV-1 RNA underquantitation or false-negative test results revealed new HIV-1 variants that were mismatched with primers and probes used in some mono-target assays. So far, dualtarget NAT assays have not been associated with mismatch-based false-negative test results. From 2015, the Paul Ehrlich Institute will request HIV-1 NAT assays of dual-target design or an analogous solution for further reducing the risk in blood screening. Conclusion: HIV differs from other blood-borne viruses with regard to its fast evolution of new viral variants. The evolution of new sequences is hardly predictable; therefore, NAT assays with only 1 target region appear to be more vulnerable to sequence variations than dual-target assays. The associated risk may be higher for HIV-1 NAT assays used for blood screening compared to quantitative assays used for monitoring HIV-1-infected patients. In HIV-1 screening NAT assays of dual-target design may adequately address the risk imposed by new HIV-1 variants.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Risk Minimization Measures for Blood Screening HIV-1 Nucleic Acid Amplification Technique Assays in Germany

Chudy

Kreß

Halbauer

et al. 2013

Transfus Med Hemother

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“…8,9 Comparisons of recent HIV viral load assays demonstrated an underestimation of 10-40% of some non-B subtypes, CRF variants, or Group N or O viruses, and reports of failure of screening tests to detect the rare subtypes have been noted. 3,[10][11][12] Subtype G and CRF02_AG, for example, are frequently missed or underquantitated. 13 Failure of HIV DNA PCR assays to correctly identify infants infected with nonsubtype B has also been reported.…”

mentioning

confidence: 99%

Pilot Studies for Development of an HIV Subtype Panel for Surveillance of Global Diversity

Manak

Sina²,

Anekella³

et al. 2012

AIDS Research and Human Retroviruses

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The continued global spread and evolution of HIV diversity pose significant challenges to diagnostics and vaccine strategies. NIAID partnered with the FDA, WRAIR, academia, and industry to form a Viral Panel Working Group to design and prepare a panel of well-characterized current and diverse HIV isolates. Plasma samples that had screened positive for HIV infection and had evidence of recently acquired infection were donated by blood centers in North and South America, Europe, and Africa. A total of 80 plasma samples were tested by quantitative nucleic acid tests, p24 antigen, EIA, and Western blot to assign a Fiebig stage indicative of approximate time from initial infection. Evaluation of viral load using FDA-cleared assays showed excellent concordance when subtype B virus was tested, but lower correlations for subtype C. Plasma samples were cocultivated with phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from normal donors to generate 30 viral isolates (50-80% success rate for samples with viral load > 10,000 copies/ml), which were then expanded to 10 7

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“…This is illustrated by the failure of existing NAT to detect rare HIV mutants [10], specific HCV genotypes [11] and, more frequently reported, viral load assays that sub and overquantify particular genotypes of HCV and HIV [12,13].…”

Section: Nat False-negatives/positivesmentioning

confidence: 99%

Current concepts in molecular testing

Levi

2011

ISBT Science Series

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

Abstract: HIV-1 increasing heterogeneity affects the efficiency of NATs and consequently the safety of the blood supply as well as diagnosis and patient management.

Cited by 32 publications

References 28 publications

Risk Minimization Measures for Blood Screening HIV-1 Nucleic Acid Amplification Technique Assays in Germany

Risk Minimization Measures for Blood Screening HIV-1 Nucleic Acid Amplification Technique Assays in Germany

Pilot Studies for Development of an HIV Subtype Panel for Surveillance of Global Diversity

Current concepts in molecular testing

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