title: Multicenter evaluation of a new automated fourth-generation human immunodeficiency virus screening assay with a sensitive antigen detection module and high specificity.
abstract: Fourth-generation assays for the simultaneous detection of human immunodeficiency virus (HIV) antigen and antibody that were available on the international market until now have antigen detection modules with relatively poor sensitivity and produce a higher rate of false-positive results than third-generation enzyme immunoassays (EIAs). The new Cobas Core HIV Combi EIA with an improved sensitivity for HIV p24 antigen was compared to alternative fourth- and third-generation assays, the p24 antigen test, and HIV type 1 (HIV-1) RNA reverse transcriptase PCR (RT-PCR). A total of 94 seroconversion panels (n = 709 sera), samples from the acute phase of infection after seroconversion (n = 32), anti-HIV-1-positive specimens (n = 730) from patients in different stages of the disease, 462 subtyped samples from different geographical locations, anti-HIV-2-positive sera (n = 302), dilutions of cell culture supernatants (n = 62) from cells infected with different HIV-1 subtypes, selected performance panels from Boston Biomedica Inc., 7,579 unselected samples from blood donors, 303 unselected daily routine samples, 997 specimens from hospitalized patients, and potentially interfering samples (n = 1,222) were tested with Cobas Core HIV Combi EIA. The new assay showed a sensitivity comparable to that of the Abbott HIV-1 AG Monoclonal A for early detection of HIV infection in seroconversion panels. The mean time delay of Cobas Core HIV Combi EIA (last negative sample plus 1 day) in comparison to that for HIV-1 RT-PCR for 87 panels tested with both methods was 2.75 days. The diagnostic window was reduced with Cobas Core HIV Combi EIA by between 3.6 and 5.7 days from that for third-generation assays. The specificities of Cobas Core HIV Combi EIA in blood donors were 99.84 and 99.85% (after repeated testing). Overall, 30 repeatedly reactive false-positive results out of 10,031 HIV-negative samples were obtained with Cobas Core HIV Combi EIA. Our results show that a fourth-generation assay with improved specificity such as Cobas Core HIV Combi EIA is suitable for blood donor screening because of its low number of false positives and because it detects HIV p24 antigen with a sensitivity comparable to that of single-antigen assays.
authors.affiliation: Laboratoires Réunis Kutter-Lieners-Hastert, Junglinster, Luxembourg. web@labo.lu
authors.forename: Bernard
authors.initials: B
authors.lastname: Weber
authors.forename: Lutz
authors.initials: L
authors.lastname: Gürtler
authors.forename: Rigmor
authors.initials: R
authors.lastname: Thorstensson
authors.forename: Ulrike
authors.initials: U
authors.lastname: Michl
authors.forename: Annelies
authors.initials: A
authors.lastname: Mühlbacher
authors.forename: Philippe
authors.initials: P
authors.lastname: Bürgisser
authors.forename: Roberto
authors.initials: R
authors.lastname: Villaescusa
authors.forename: Adolfo
authors.initials: A
authors.lastname: Eiras
authors.forename: Christian
authors.initials: C
authors.lastname: Gabriel
authors.forename: Herbert
authors.initials: H
authors.lastname: Stekel
authors.forename: Srivilai
authors.initials: S
authors.lastname: Tanprasert
authors.forename: Sinenaart
authors.initials: S
authors.lastname: Oota
authors.forename: Maria-Jose
authors.initials: MJ
authors.lastname: Silvestre
authors.forename: Cristina
authors.initials: C
authors.lastname: Marques
authors.forename: Maria
authors.initials: M
authors.lastname: Ladeira
authors.forename: Holger
authors.initials: H
authors.lastname: Rabenau
authors.forename: Annemarie
authors.initials: A
authors.lastname: Berger
authors.forename: Urban
authors.initials: U
authors.lastname: Schmitt
authors.forename: Walter
authors.initials: W
authors.lastname: Melchior
mesh_terms: D015492:AIDS Serodiagnosis; D001782:Blood Donors; D015483:HIV Antibodies / Q000097:blood; D015488:HIV Antigens / Q000097:blood*; D016655:HIV Core Protein p24 / Q000097:blood*; D015658:HIV Infections / Q000175:diagnosis*; D015497:HIV-1 / Q000302:isolation & purification; D015498:HIV-2 / Q000302:isolation & purification; D006801:Humans; D007124:Immunoenzyme Techniques; D008403:Mass Screening; D012367:RNA, Viral / Q000097:blood; D011933:Reagent Kits, Diagnostic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D015483:HIV Antibodies; D015488:HIV Antigens; D016655:HIV Core Protein p24; D012367:RNA, Viral; D011933:Reagent Kits, Diagnostic