Michael Chudy1, Julia Kress1, Jochen Halbauer2, Margarethe Heiden3, Markus B Funk2, C Micha Nübling1. 1. Section of Molecular Virology, Paul-Ehrlich-Institut, Langen, Germany. 2. Section of Hemovigilance and IVD Vigilance, Paul-Ehrlich-Institut, Langen, Germany. 3. Section of Transfusion Medicine, Paul-Ehrlich-Institut, Langen, Germany.
Abstract
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.
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-infectedpatients. In HIV-1 screening NAT assays of dual-target design may adequately address the risk imposed by new HIV-1 variants.
Authors: F Damond; V Avettand-Fenoel; G Collin; B Roquebert; J C Plantier; A Ganon; D Sizmann; R Babiel; J Glaubitz; M L Chaix; F Brun-Vezinet; D Descamps; C Rouzioux Journal: J Clin Microbiol Date: 2010-02-03 Impact factor: 5.948
Authors: Dorothea Sizmann; Joachim Glaubitz; Christian O Simon; Sebastian Goedel; Philippe Buergisser; Daniel Drogan; Martin Hesse; Michael Kröh; Pascale Simmler; Manuela Dewald; Marion Gilsdorf; Marion Fuerst; Ralph Ineichen; Anette Kirn; Paul Pasche; Zhijun Wang; Sabrina Weisshaar; Karen Young; Gerd Haberhausen; Reiner Babiel Journal: J Clin Virol Date: 2010-07-15 Impact factor: 3.168
Authors: C Micha Nübling; Margarethe Heiden; Michael Chudy; Julia Kress; Rainer Seitz; Brigitte Keller-Stanislawski; Markus B Funk Journal: Transfusion Date: 2009-05-14 Impact factor: 3.157
Authors: Benjamin Müller; C Micha Nübling; Julia Kress; W Kurt Roth; Silke De Zolt; Lutz Pichl Journal: Transfusion Date: 2013-06-19 Impact factor: 3.157
Authors: Silke De Zolt; Rolf Thermann; Thorsten Bangsow; Lutz Pichl; Benjamin Müller; Christine Jork; Marijke Weber-Schehl; Doris Hedges; Ingo Schupp; Patrick Unverzagt; Katrin de Rue; W Kurt Roth Journal: Transfus Med Hemother Date: 2016-05-11 Impact factor: 3.747