Performance of three automated fourth-generation combined HIV antigen/antibody assays in large-scale screening of blood donors and clinical samples
¨ ¨ K. Malm,* M. von Sydow† & S. Andersson*‡ *Department of Clinical Microbiology, Orebro University Hospital, Orebro, †Department of ClinicalMicrobiology, Karolinska University Hospital, Solna, and ‡Department of Virology, Swedish Institute for Infectious Disease Control, Stockholm, Sweden Received 22 February 2008; accepted for publication 10 October 2008
Since the introduction in the mid-1980s, HIV testing has gradually improved both in terms of sensitivity and specificity. The so-called fourth generation of tests,combined HIV antigen/antibody assays, has now been introduced. This study compares three automated combined assays with older third-generation antibody assays in large-scale screening. Serum samples from routine screening of blood and plasma donors and clinical samples were investigated for specificity evaluation. Three fourth-generation combination assays from one manufacturer were compared with threeolder third-generation antibody assays from the same manufacturer. More than 40 000 samples per assay were included. For sensitivity, selected panels of confirmed HIV-1- and HIV-2-positive samples as well as seroconversion samples (HIV-1) from commercial panels and also from patients who appeared during the evaluation were used. The specificities of the fourth-
generation tests were 99Á91%(AxSYM), 99Á95% (ARCHITECT) and 99Á97% (PRISM) after repeated testing. Some specificity variation between reagent batches was observed. All HIV-1-positive samples were reactive by the three fourth-generation systems. HIV-1 seroconversion samples and panels were reactive earlier than by antibody-only tests. As for HIV-2 samples, AxSYM failed to detect one (n ¼ 40), whereas PRISM and ARCHITECTdetected all (n ¼ 16 for PRISM and n ¼ 52 for ARCHITECT). The new HIV antigen/ antibody combination assay systems were found to have high sensitivity and specificity. The instruments provided a rational and easy way of testing at large scale. Key words: antigen/antibody combination assays, blood donors, evaluation, fourth-generation assays, HIV.
Since the introduction in the mid-1980s, HIV testinghas gradually improved both in terms of sensitivity and specificity. While the first generation of assays was usually based on whole viral lysate in an indirect enzyme-linked immunosorbent assay (ELISA) format, subsequent generations included more sensitive and specific recombinant and synthetic peptide antigens (so-called second-generation assays) as well as sandwich assay formats (thirdgeneration) allowing simultaneous detection of both immunoglobulin G and
Correspondence: Kerstin Malm, Department of Clinical ¨ ¨ Microbiology, Orebro University Hospital, S-701 85 Orebro, Sweden. Tel.: 146196021134; fax: 14619127416; e-mail: email@example.com
immunoglobulin M antibodies. With the increasing sensitivity of the assays, the diagnostic window period from the time of infectionuntil the test becomes positive has gradually decreased to around 3–4 weeks, i.e. 1–2 weeks after primary HIV infection (PHI) for the third-generation assays (Thorstensson et al., 1998; Lindback et al., 2000). Separate HIV antigen assays are ¨ able to detect recent HIV infection a few days before onset of PHI and nucleic acid testing (NAT) around 1 week before PHI (i.e. around 1 week after the timeof infection) (Weber, 2006). More recently, combined HIV antigen/antibody assays have been introduced (fourth generation). A standard ELISA format for large-scale testing is typically based on microtitre plates for the solid phase. In centres handling larger numbers of specimens, the
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Performance of HIV...