A rapid, point-of-care test, which aims to reduce the ‘window period’ through the detection of both antibodies and p24 antigen has poor performance in a UK clinical setting, Clifford Bryn Jones and colleagues report in the advance online edition of the Journal of Infectious Diseases.
These data appear to confirm previous reports that while the Determine HIV-1/2 Ag/Ab Combo can reliably identify people with established HIV infection, it delivers false negative results to most people who have very recent HIV infection.
Rapid diagnostic tests, which can be operated at the point-of-care by doctors or nurses, offer numerous advantages over conventional laboratory tests. Such devices are essential in resource-limited settings where laboratories are inaccessible or unavailable. Furthermore, as patients do not need to come back for their results on another day, far more people receive their results.
However almost all rapid tests only detect HIV antibodies, which are only detectable approximately one month after infection. In contrast, tests conducted in a laboratory may also be able to detect p24 antigen or HIV RNA, both of which are detectable earlier than this. These tests therefore shorten the ‘window period’.
Introduced in 2009, the Determine HIV-1/2 Ag/Ab Combo is the only rapid test which combines detection of antibodies and p24 antigen.
However, earlier this year, researchers working in Malawi reported that the test’s actual performance in relation to recent infections was inadequate, echoing a smaller UK study published the previous year.
Clinicians in London compared the testing results from three different types of HIV test:
- a combination laboratory test that looks for both antibodies and p24 antigen (Abbott Architect),
- an antibody-only rapid test (Determine HIV-1/2 Ag/Ab), and
- the combination rapid test that looks for both antibodies and p24 antigen (Determine HIV-1/2 Ag/Ab Combo).
Samples were taken from 985 high-risk individuals seeking testing at St Mary’s Hospital. The vast majority were men who have sex with men (817), with most others coming from high-prevalence countries (153).
Using the laboratory test as a benchmark, 22 people were HIV positive (2.3% prevalence). Two of these individuals were only identified by the p24 antigen part of the laboratory test – they were not yet positive for antibodies because they had very recent infection, although they did not have any seroconversion symptoms.
As expected, the antibody-only rapid test identified the 20 HIV-positive people with antibodies, but not the two individuals who only had p24 antigen.
However, the fourth-generation rapid test also failed to identify those two individuals with p24 antigen only (very recent infection), and only diagnosed 19 of the 22 HIV-positive people. Moreover, three additional individuals tested positive for p24 antigen with the rapid test, but their results were not confirmed by the more reliable laboratory testing.
The researchers calculate the sensitivity of the combination rapid test to be 90.5% (95% confidence interval 69.6% - 98.8%). A test’s sensitivity refers to its ability to correctly diagnose people with infection.
On the other hand, its specificity was more acceptable at 99.8% (95% confidence interval 99.2% - 99.9%). A test’s specificity refers to its ability to correctly deliver negative results.
As in the previous report from Malawi, it appears that the antibody part of the rapid test does have excellent sensitivity and specificity, but that the p24 antigen part – its unique selling point – performs poorly.
Moreover, French researchers also report in the same journal that the test is unable to detect p24 consistently, especially with non-B subtypes such as F, G, H, J, O and P, and never with HIV-2.
Commenting on these new data, the investigators behind the Malawi study say that while the performance of this test is disappointing, the goal of identifying people during acute infection is important. “Investigators and industry should work together towards designing sensitive and specific diagnostics capable of detecting acute HIV infection at the point of care. These diagnostics must then be field tested before clinical use, regardless of the degree of difficulty involved.”
Jones CB et al. Clinical Evaluation of the Determine HIV-1/2 Ag/Ab Combo test. Journal of Infectious Diseases, doi:10.1093/infdis/jis628, 2012.
Laperche S et al. Failures in the detection of HIV p24 antigen with Determine® HIV-1/2 Ag/Ab Combo rapid test. Journal of Infectious Diseases, doi:10.1093/infdis/jis616, 2012.
Rosenberg NE et al. Point-of-Care Diagnostics for Acute HIV Infection: An Important Public Health Priority. Journal of Infectious Diseases, doi:10.1093/infdis/jis618, 2012.