Accuracy

Comparison tests between different rapid tests often show a wide range in performance, with some tests being much less sensitive and specific than others.1 2 3 4 5

Rapid tests that use oral fluid (saliva) rather than blood may be subject to more sampling variation, influencing the sensitivity of the test.6

Moreover, whereas test results are often reported for serum or plasma, these are rarely the samples used in everyday practice. Results for whole (fingerprick) blood tend to be slightly less favourable.

One comparison of six rapid tests found that HIV-positive samples which had false-negative results were more likely to be from individuals with an HIV viral load of less than 200 copies/ml.5

As with any other test, a reactive ('positive') result must be confirmed with a confirmatory test. This approach greatly increases the accuracy of the testing process.

Determine HIV-1/2

A 1998 evaluation of Determine HIV-1/2 by the Health Protection Agency found that it was the second most sensitive rapid test (of 13 tested) and was almost as sensitive as some laboratory-based methods. Specificity was 100%.4

An evaluation of Determine for the World Health Organization found that, against 250 samples, it had a sensitivity of 100% (95% confidence limit 95.5%-100%) and a specificity of 99.4% (96.7%-100%). It detected HIV about three days later than the most sensitive third-generation test. It scored highly for ease of use.2

A validation study by the Chelsea and Westminster Hospital, enrolling 1623 people, found that the sensitivity of Determine – the ability to detect all true positive results – was 100% (95% CI: 95.3-100%) and the test’s specificity – the number of negative tests correctly identified as negative – was 99.9% (CI: 99.5-100%). There were no false negative tests, but there were two false positive results, which were picked up on standard confirmatory testing.7

An evaluation by the French regulatory agency found that Determine correctly identified 100 of 100 HIV-positive samples and 49 of 50 HIV-negative samples. In terms of detecting acute infection, it correctly identified 11 of 15 samples. In terms of ease of use, the test scored 18 marks out of 26.8

A French study tested Determine against 200 HIV-positive samples, and found that it had a sensitivity of 94.9%.5

Evaluation of the use of Determine at Terrence Higgins Trust outreach sites found that of 50 people who tested positive, there was one false positive (probably due to another viral infection at the time of the test).9 10

However, a study from Uganda highlighted problems with the specificity of Determine, in other words a high rate of false positives. In this setting, reactive results from Determine were confirmed with two other rapid tests (neither of which are available in the UK), and a result was considered positive if all three tests agreed. The samples were then re-tested with third-generation ELISAs and Western Blots to confirm that the diagnosis was true.

Based on 1517 samples, the sensitivity of this sequence of tests was 97.7% and the specificity was 90.4% (in other words, of 1000 HIV-negative people, 96 were incorrectly diagnosed as positive). The researchers identified that part of the problem stemmed from ‘weakly positive’ results, in other words when the testing device gave a weak signal that the manufacturer had nonetheless said should be interpreted as positive. When the ‘weakly positive’ results were excluded, the sensitivity and specificity improved to 99.6% and 97.7% respectively. The researchers concluded that the tests need to be interpreted differently, and reactive (positive) results confirmed by traditional methods.11

The manufacturer claims a sensitivity of 100% and a specificity of 99.75%.

Higher rates of indeterminate results have been reported when testing pregnant women.12

Determine HIV-1/2 Ag/Ab Combo

The first ever fourth-generation test in a rapid format was introduced in 2009. This assay looks for both antibodies and p24 antigen, hopefully reducing the window period. Moreover, unlike most laboratory fourth-generation tests, it has separate indicators for antibodies and p24 antigen.

The manufacturer reports that the assay was evaluated on 1179 positive and 2343 negative samples. Sensitivity was 100% (95% confidence interval 98.04-100%), and specificity was 99.2% (98.9-99.6%).

The ability to detect p24 allowed for the identification of people in primary infection an average of 5 days (range: two to 20 days) before the previous Determine test.

However, other research suggests limitations to the test, specifically its ability to detect primary infection. This may be because a point-of-care test in the ‘lateral flow’ format has a much lower level of sensitivity to p24 antigen than modern laboratory tests, which are able to detect lower concentrations.

While researchers in Malawi found that the test reliably detected antibodies in established HIV infection (sensitivity 99.4% and specificity 99.2%), results were inadequate in relation to eight individuals who had acute infection. Only two of the eight were identified by the test, giving a sensitivity of 25% (95% confidence interval 3.2-65.1%). Moreover, these two individuals tested positive for HIV antibodies, and not for p24 antigen. While this does suggest that the antibody part of the test performs better than some other antibody tests, the p24 antigen part of the test performed poorly – but the detection of p24 antigen is key to identifying people who have recent infection.

Moreover, when the test was performed on 838 HIV-negative samples, 14 of the results for p24 antigen were false positives, further undermining the usefulness of the test in this setting.13

UK researchers tested the Determine Combo test on stored samples from 36 people with HIV, each of whom had detectable p24 according to laboratory tests. Ten of them had detectable antibodies, while 26 did not (in other words, they had acute infection).

Overall, the rapid test detected p24 antigen for only half those tested, giving a sensitivity of 50% (95% confidence interval 34-66%).The test failed to detect HIV infection (either via p24 antigen or antibodies) in ten of 36 cases, nine of whom had acute infection.14

Another study tested the kit with stored samples from 18 women who seroconverted during pregnancy. While the antibody part of the test was reactive for 16 women (sensitivity 88.9%), the p24 antigen part of the test was reactive for none of the women (0%).

A French study tested the kit against 200 HIV-positive samples, and found that it had a sensitivity of 95.8%. Two samples of people in primary infection were not detected. In addition, in 33 cases, the first test performed could not be read (results are considered invalid if an internal control bar does not appear).5 Other clinicians have also had problems with results that could not be read.15

More encouragingly, a study from San Francisco assessed the performance of the combo test against samples from gay men testing during primary infection. Sensitivity in this population was 96%, which was superior to the performance of third-generation tests used in the study, and a little lower than a laboratory fourth-generation test (98%).16

INSTI

An evaluation by the French regulatory agency found that INSTI correctly identified all 100 HIV-positive samples and all 50 HIV-negative samples. In terms of detecting acute infection, it performed well in comparison with other rapid tests, with 12 of 15 samples correctly identified. In terms of ease of use, the test scored 18 marks out of 26.17

Another French study tested the INSTI against 200 HIV-positive samples, and found that it had a sensitivity of 99%.5

In the manufacturer’s studies which led to INSTI being approved by the FDA, its accuracy was tested with 1097 HIV-positive and 1382 uninfected samples of finger-prick blood. Sensitivity was 99.8% (95% confidence interval 99.3-99.9%) and specificity was 99.5% (95% confidence interval 99.0-99.8%).18

Although INSTI contains proteins to test for both HIV-1 and HIV-2, the validation studies which led to its approval in the United States only tested its ability to detect HIV-1. As such, it is not approved by the Food and Drugs Administration (FDA) for the detection of HIV-2.

The manufacturer warns that people with malignant tumours of the bone marrow and people with elevated haemoglobin levels may get false negative results with the test.

VIKIA

An HPA evaluation of the VIKIA HIV1/2 test, using a limited number of samples, found that it had a sensitivity of 100% and specificity of 100%. VIKIA was compared to the Determine antibody test in its ability to identify infection in blood samples of people seroconverting. Vikia detected seroconversion a mean of 2.8 days later, but performed significantly better than two non-CE marked rapid tests that were tested at the same time.19 

An evaluation by the French regulatory agency found that VIKIA correctly identified all 100 HIV-positive samples and all 50 HIV-negative samples. In terms of detecting acute infection, it performed poorly in comparison with other rapid tests, with 10 of 15 samples correctly identified. In terms of ease of use, the test scored relatively well, with 22 marks out of 26.17

A French study tested VIKIA against 200 HIV-positive samples, and found that it had a sensitivity of 98.5%.5

When used with whole blood, the manufacturer claims a sensitivity of 99.95% and a specificity of 99.86%.

Core

An evaluation by the French regulatory agency found that Core correctly identified 98 of 100 HIV-positive samples and all 50 HIV-negative samples. In terms of detecting acute infection, it performed poorly in comparison with other rapid tests, with 10 of 15 samples correctly identified. In terms of ease of use, the test scored relatively well, with 20 marks out of 26.17

HPA evaluation of the device against seroconversion panels found that it had similar performance to Determine, but was superior to some other devices tested. Sensitivity and specificity were not evaluated.20

The manufacturer claims a sensitivity of 100% and a specificity of 99.75%.

Immunoflow

An evaluation by the French regulatory agency found that Immunoflow correctly identified 99 of 100 HIV-positive samples and all 50 HIV-negative samples. In terms of detecting acute infection, it performed well in comparison with other rapid tests, with 13 of 15 samples correctly identified. In terms of ease of use, the test scored relatively well, with 21 marks out of 26.17

HPA evaluation of the device against seroconversion panels found that it had similar performance to Determine, but was superior to some other devices tested. Sensitivity and specificity were not evaluated.21

The manufacturer claims a sensitivity of 100% and a specificity of 100%.

OraQuick Advance Rapid HIV-1/2

OraQuick is one of only two rapid devices that are approved for use in the United States and also marketed in the UK. Because of its position in the American market, its effectiveness has been more widely examined than that of some other rapid devices. Some problems, including false positive results and limited sensitivity in people with recent infection, have been identified.

More problems have occured when the test is used with oral fluid ('saliva') than when used with fingerprick blood, venepuncture blood, plasma or serum.

The CDC reported on their experience of using OraQuick in two separate reports in 2006. The ‘four studies’ pooled data from over 12,000 people.22 Post-marketing surveillance tracked the use of OraQuick with over 160,000 people.23 Both papers suggested that their experience of using OraQuick was broadly consistent with the manufacturer’s trial data. Additional data comes from a smaller WHO study.2 

Evaluations of OraQuick

Sample

Study

Sensitivity

Specificity

Whole blood

Manufacturer

100%

100%

CDC four studies

99.7%

99.9%

CDC surveillance

99.7%

99.98%

Serum

WHO

98.1%

100%

Oral fluid

Manufacturer

100%

99.8%

CDC four studies

99.1%

99.6%

CDC surveillance

99.6%

99.89%

Source: See above for source details

However, there have also been unexplained clusters of false positive results (i.e. lower specificity) at specific locations. These problems were reported as part of the CDC studies cited above, and in a separate report:

  • During a five-month period in Minnesota, specificity dropped to 95.9%. 22
  • During a nine-month period at one location in San Francisco, specificity dropped to 98.7%.23
  • In New York, the specificity each month ranged from 98.88% to 99.98%.24 

In each case, the problems arose with the oral fluid samples, and not the blood samples. Investigation into manufacturing problems and compliance with operating procedures failed to identify causes for the increase in false positives, though unknown operator errors are a possibility.

The authors of these reports stress the need to confirm initial positive results with confirmatory testing; pre-test discussion so that people who are testing are aware of the need for confirmation; quality-assurance procedures to monitor compliance with operating procedures and test performance; and the importance of alerting the manufacturer to increases in false positives.

In London, evaluation by Barts and The London NHS Trust on the effectiveness of OraQuick with sexual health patients considered ‘high-risk’ (HIV prevalence 5.7%), found that the test’s sensitivity was 93.6% (95% CI 82.5-98.7%), its specificity 99.9% (99.3-100%). The three false negatives were considered to be due to observer error; further training increased test sensitivity to 100%.25

A French study tested the kit against 200 HIV-positive blood samples, and found that it had a sensitivity of 94.5%. However, when testing saliva samples from the same individuals, sensitivity dropped further to 86.5%.5

A CDC study, comparing OraQuick with other rapid tests that are used in the United States, found that performance was good. The test was used with 5789 people testing for HIV in Los Angeles. With whole blood samples, sensitivity was 97.7% (95% CI 95.1-99.1%) and specificity 99.98% (95% CI 99.89-100%). The test was less able to detect people with HIV who tested with oral fluid – sensitivity 96.2% (95% CI 93.2-98.2%). With oral fluid, specificity was 99.96% (95% CI 99.86-100%).26

A study in Washington DC, based on 3717 tests, found that specificity was 99.7%.27

A number of reports indicate limitations of OraQuick in diagnosing people who have acute HIV infection (in other words, very recent infection, usually defined as the person being positive for HIV RNA but negative for at least one antibody test). One CDC study found that of 32 individuals who had acute infection, 21.9% had reactive results with OraQuick. These results are comparable to those of the other rapid tests (none of which are marketed in the UK) included in the study. As a point of comparison, a third-generation lab test detected 54.8% of the acute infections and a fourth-generation lab test detected 87.5%.28

In a similar study, only one of 42 samples from people with acute infection was identified by OraQuick, but none of the rapid tests evaluated performed well in this respect.1

A San Francisco study assessing the performance of OraQuick Advance against samples from gay men testing during primary infection found that the test had poor sensitivity (86%) when using saliva samples, but did better when blood samples were tested (92%).16 

Another study, conducted among gay men in Seattle, including high numbers of men during primary infection, found that the sensitivity of OraQuick was only 80%. A mix of saliva and blood samples were taken.29 Other studies have found that OraQuick was only able to identify one of 43 samples from people with recent infection1 and that OraQuick was unable to detect seroconverters any sooner than a Western Blot, which has a window period of approximately five weeks.30 Because OraQuick relies on detecting antibody to gp41 any delay in producing this antibody could reduce the sensitivity of the test in early infection.31

The manufacturer claims that OraQuick detects people with recent infection an average of 2.5 days (95% confidence limit: 1.2 to 3.8 days) after a third-generation test.

There has also been a case report of a situation in which a man with late-stage AIDS was given repeated false negative results with OraQuick. The 28-year-old man had oral candidiasis and PCP and was tested using oral fluids several times over a nine-month period. Each test was negative, but standard tests later confirmed HIV infection. The man had a CD4 count of 4 cells/mm3 and a viral load >100,000 copies/ml.

Examination of the the Western blot results showed a strong gp160 band, but other bands, including gp41, were very weak. Because the OraQuick test contains only a single glycoprotein antigen (anti-gp41), it will not identify HIV-infected individuals who fail to mount a substantial response to that particular antigen. These individuals may include the newly infected as well as people with such late-stage infection that their antibody responses to HIV have been compromised by the infection itself.32

Similar problems could occur with other rapid tests; if symptoms suggest HIV infection, but results of a rapid test are non-reactive, confirmatory laboratory tests should be used.

More positively, evaluation of OraQuick in southern Africa (where subtype C is most common) found that it had a sensitivity of 100% (95% confidence interval 94.9%-100%) and a specificity of 100% (98.2%-100%).33

A WHO report rated OraQuick highly for ease of use.2

References

  1. Louie B et al. Assessment of rapid tests for detection of human immunodeficiency virus-specific antibodies in recently infected individuals. J Clin Microbiol 46:1494-97, 2008
  2. World Health Organization Department of Essential Health Technologies HIV assays: Operational Characteristics, report 12. WHO, 2002
  3. World Health Organization Department of Essential Health Technologies HIV assays: Operational Characteristics, report 14. WHO, 2004
  4. Giles RE et al. Abbott Determine HIV-1/2 - a simple/rapid test device. HPA Midas, 1998
  5. Pavie J et al. High rates of false negative results with oral fluid and blood specimens using different kits of rapid testing for HIV diagnosis. 5th IAS Conference, Cape Town, abstract MOPDB104, 2009
  6. Poljak M et al. 2008 European Guideline on HIV Testing. IUSTI / WHO, 2008
  7. Dewsnap C et al. Piloting the use of Rapid HIV testing. 2nd Joint Meeting BASHH/ASTDA, Bath, 2004
  8. Haute autorité de santé HIV infection screening in France: Screening Strategies. Retrieved January 19, 2012, from www.has-sante.fr, 2009
  9. Weatherburn P et al. Evaluation of the Department of Health funded fasTest HIV testing in the community pilot. Sigma Research, 2006
  10. Weatherburn P et al. Evaluation of the gsk funded fasTest HIV testing in the community pilot. Sigma Research, 2006
  11. Gray RH et al. Limitations of rapid HIV-1 tests during screening for trials in Uganda: diagnostic test accuracy study. BMJ 335 (7612):188, 2007
  12. Matemo J Indeterminate rapid HIV-1 test results among antenatal and postnatal mothers. International Journal of STD & AIDS, 790-2, 2009
  13. Rosenberg N Detection of Acute HIV Infection: A Field Evaluation of the Determine® HIV-1/2 Ag/Ab Combo Test. Journal of Infectious Diseases, online ahead of print, 2011
  14. Fox J Low rates of p24 antigen detection using a fourth-generation point of care HIV test. Sexually Transmitted Infections, 178-179, 2011
  15. Naylor E Fourth generation point of care testing for HIV: validation in an HIV-positive population. Sexually Transmitted Infections, 311, 2011
  16. Pilcher CD et al. A clinical study of antigen-antibody rapid testing for acute HIV infection. 16th CROI, Montreal, Abstract 992, 2009
  17. Haute autorité de santé HIV infection screening in France: Laboratory tests and algorithms. Retrieved January 19, 2012, from http://www.has-sante.fr/portail/upload/docs/application/pdf/2010-02/hiv_infection_screening_in_france_-_laboratory_tests_and_algorithms-conclusions.pdf, 2008
  18. bioLytical Laboratories Inc. Summary of Safety and Effectiveness Data - INSTI HIV-1 Antibody Test. Retrieved January 5, 2011, from www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/PremarketApprovalsPMAs/ucm235024.htm, 2010
  19. Gonen G et al. Evaluation of the VIKIA HIV 1/2 rapid test. Health Protection Agency Microbiological Diagnostics Assessment Service, 2008
  20. Dean L et al. An assessment of the seroconversion sensitivity of Core Diagnostics HIV1&2 rapid test device. Health Protection Agency Microbiological Diagnostics Assessment Service, 2003
  21. Gonen G et al. An assessment of the seroconversion sensitivity of ImmunoFlow HIV1-HIV2 rapid test device. Health Protection Agency Microbiological Diagnostics Assessment Service, 2006
  22. Delaney KP et al. Performance of an oral fluid rapid HIV-1/2 test: experience from four CDC studies. AIDS 20:1655-1660, 2006
  23. Wesolowski LG et al. Post-marketing surveillance of OraQuick whole blood and oral fluid rapid HIV testing. AIDS 20:1661-1666, 2006
  24. Cummiskey J et al. False-positive oral fluid rapid HIV tests-New York City, 2005-2008. MMWR 57:660-665, 2008
  25. Zelin J et al. An evaluation of the performance of OraQuick ADVANCE Rapid HIV-1/2 Test in a high-risk population attending genitourinary medicine clinics in East London, UK. Int J STD AIDS 19:665-7, 2008
  26. Delaney K Evaluation of the Performance Characteristics of 6 Rapid HIV Antibody Tests. Clinical Infectious Diseases, 257-263, 2011
  27. Rexroth K Rapid Oral HIV Screening: Expectations Revisited. Journal of Acquired Immune Deficiency Syndromes, e59-e60, 2011
  28. Patel P Rapid HIV screening: missed opportunities for diagnosis and prevention. 17th Conference on Retroviruses and Opportunistic Infections, 2010
  29. Stekler J et al. Limitations of rapid HIV antibody testing in a population with high incidence of HIV infection. 16th CROI, Montreal, Abstract 990, 2009
  30. Owen SM et al. Alternative Algorithms for Human Immunodeficiency Virus Infection Diagnosis Using Tests That Are Licensed in the United States. J Clin Microbiol 46:1588-1595, 2008
  31. Coombs RW Clinical laboratory diagnosis of HIV-1 and use of viral RNA to monitor infection. In Holmes KK (editor), Sexually Transmitted Diseases. New York: McGraw-Hill, 2008
  32. Brown P et al. Repeatedly false-negative rapid HIV test results in a patient with undiagnosed advanced AIDS. Ann Intern Med 149:71, 2008
  33. Hamers RL et al. Diagnostic accuracy of 2 oral fluid-based tests for HIV surveillance in Namibia. J Acquir Immune Defic Syndr 48: 116-118, 2008
This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.