Dear Editor
Fox, Dunn and O'Shea stressed the importance of diagnosing primary
HIV infecting (PHI) to prevent onward transmission and help control the
HIV epidemic1. They evaluated the 4th generation HIV-1/2 Ag/Ag Determine
Combo assay (Alere) for its ability to detect p24 antigen as a marker of
PHI and have shown its poor sensitivity in detecting PHI and recommended
further evaluations of the assay. Many patients self present to sexual
health clinics for a STI screen soon after an exposure which they perceive
as risky. Many clinics now offer rapid point of care (POCT) HIV testing
and although they are generally aware of the insensitivity of the 3rd
generation (antibody only) tests for PHI diagnosis, they could easily
assume that the new Determine Assay is equivalent in sensitivity to the
4th generation EIAs.
We performed a similar evaluation of the Determine assay at the HPA
Birmingham Public Health Laboratory and recently presented our findings at
the European Society for Clinical Virology winter meeting in London2.
Stored plasma samples were selected from patients who are at risk for HIV-
1 and who were screened between April 2008 and May 2010 using our routine
laboratory assays (Genscreen ULTRA HIV Ag-Ab Assay - Bio-Rad Laboratories
-, VIDAS HIV Duo Ultra HIV5, VIDAS HIV Duo Quick HIV6 p24 assay -
Biomerieux, Marcy l'Etoile, France). We selected 21 samples from patients
who either were diagnosed with acute HIV-1 seroconversion (14 samples) or
had a false positive reaction in one of our screening EIAs (7 samples).
All the samples were classified as either true seroconversion or false
positive by means of follow up samples. All samples were either p24 Ag
positive or equivocal. The definition of equivocal was a p24 Ag signal
value on the Vidas which was too low to be neutralised. For samples which
had enough serum a Vidas p24 Ag neutralising assay was performed of which
7/10 neutralised. All 7 false positive p24 Ag sera were correctly
identified by the Determine Combo test as negative. 5/14 of the p24 Ag
true positive sera (early seroconversion) were missed by the Determine
Combo test and tested negative for both p24 Ag and antibodies i e 64%
sensitivity compared to current laboratory EIA screening methods.
Even though there is a 64% improvement over a third generation (Ab
only) POCT, health care professionals should still be aware that the
Determine HIV-1/2 Ag/Ab Combo is not as sensitive as 4th generation EIAs
in diagnosing primary HIV-1 infections.
Erasmus Smit MBChB, DTM&H, MMed (virol), FC Path (SA)
Consultant Virologist
Husam Osman MBBCh, PhD, FRCPath
Consultant Virologist
HPA Birmingham, Public Health Laboratory
Heartlands Hospital
Birmingham
B9 5SS
Reference:
1. Fox J, Dunn H, O'Shea S. Low rate of p24 antigen detection using a
fourth generation point of care HIV Test. Sex Transm Infect 2010,Nov 17
2. Smit E, Atherton C, Osman H. Determine HIV-1/2 /Ab/Ag Combo lacks
sensitivity in detecting early HIV infections. European Society for
Clinical Virology Winter meeting, London, 13-15 Jan 2011.
Conflict of Interest:
None declared
Dear Editor
Fox, Dunn and O'Shea stressed the importance of diagnosing primary HIV infecting (PHI) to prevent onward transmission and help control the HIV epidemic1. They evaluated the 4th generation HIV-1/2 Ag/Ag Determine Combo assay (Alere) for its ability to detect p24 antigen as a marker of PHI and have shown its poor sensitivity in detecting PHI and recommended further evaluations of the assay. Many patients self present to sexual health clinics for a STI screen soon after an exposure which they perceive as risky. Many clinics now offer rapid point of care (POCT) HIV testing and although they are generally aware of the insensitivity of the 3rd generation (antibody only) tests for PHI diagnosis, they could easily assume that the new Determine Assay is equivalent in sensitivity to the 4th generation EIAs.
We performed a similar evaluation of the Determine assay at the HPA Birmingham Public Health Laboratory and recently presented our findings at the European Society for Clinical Virology winter meeting in London2. Stored plasma samples were selected from patients who are at risk for HIV- 1 and who were screened between April 2008 and May 2010 using our routine laboratory assays (Genscreen ULTRA HIV Ag-Ab Assay - Bio-Rad Laboratories -, VIDAS HIV Duo Ultra HIV5, VIDAS HIV Duo Quick HIV6 p24 assay - Biomerieux, Marcy l'Etoile, France). We selected 21 samples from patients who either were diagnosed with acute HIV-1 seroconversion (14 samples) or had a false positive reaction in one of our screening EIAs (7 samples). All the samples were classified as either true seroconversion or false positive by means of follow up samples. All samples were either p24 Ag positive or equivocal. The definition of equivocal was a p24 Ag signal value on the Vidas which was too low to be neutralised. For samples which had enough serum a Vidas p24 Ag neutralising assay was performed of which 7/10 neutralised. All 7 false positive p24 Ag sera were correctly identified by the Determine Combo test as negative. 5/14 of the p24 Ag true positive sera (early seroconversion) were missed by the Determine Combo test and tested negative for both p24 Ag and antibodies i e 64% sensitivity compared to current laboratory EIA screening methods.
Even though there is a 64% improvement over a third generation (Ab only) POCT, health care professionals should still be aware that the Determine HIV-1/2 Ag/Ab Combo is not as sensitive as 4th generation EIAs in diagnosing primary HIV-1 infections.
Erasmus Smit MBChB, DTM&H, MMed (virol), FC Path (SA) Consultant Virologist
Husam Osman MBBCh, PhD, FRCPath Consultant Virologist
HPA Birmingham, Public Health Laboratory Heartlands Hospital Birmingham B9 5SS
Reference: 1. Fox J, Dunn H, O'Shea S. Low rate of p24 antigen detection using a fourth generation point of care HIV Test. Sex Transm Infect 2010,Nov 17
2. Smit E, Atherton C, Osman H. Determine HIV-1/2 /Ab/Ag Combo lacks sensitivity in detecting early HIV infections. European Society for Clinical Virology Winter meeting, London, 13-15 Jan 2011.
Conflict of Interest:
None declared