HIV and STI point-of-care tests in remote communities

HIV Australia | Vol. 11 No. 3 | October 2013

By James Ward,1, 2 Lisa Natoli,2, 3 Louise Causer, 2 John Kaldor2 and Rebecca Guy2  on behalf of the TTANGO Investigator Team


Sexually transmissible infection (STI) and HIV point-of-care tests (otherwise known as rapid tests) can be used at patient visits to test for STIs and HIV, rather than sending off a sample to the laboratory and waiting for the results.

Point-of-care tests provide advantages. They can:

  • improve immediate clinical decision making;
  • result in better compliance for hard to reach patients;
  • reduce loss to follow-up; and
  • be used for outreach, and remove pathology access barriers in some remote or rural settings.

There are also some potential challenges of using point-of-care tests:

  • They may increase workload for clinicians;
  • They may not be as accurate as standard laboratory tests; and
  • They require systems to be set up to ensure the tests are being done correctly – quality management.

While lateral flow or ‘dipstick’ devices similar to pregnancy tests are the most familiar point-of-care tests, a range of other tests are also available that can be used at the point of care.

According to the World Health Organization (WHO) ‘ASSURED’ criteria,1 an ideal point-ofcare test should be:

  1. affordable
  2. sensitive (few false negatives)
  3. specific (few false positives)
  4. user-friendly
  5. robust and rapid
  6. equipment free
  7. deliverable to those who need them.

Thus, introduction of HIV and sexually transmissible infection (STI) point-of-care tests in any setting needs careful consideration of the potential benefits in the target population.

In this article we discuss the role of HIV and STI point-of-care tests in remote Aboriginal and Torres Strait Islander communities.

HIV point-of-care tests

Lateral flow HIV point-of-care tests are used in most resource limited settings and also some resource rich settings to improve access to HIV testing and HIV treatment.

In Australia, there was limited use of HIV point-of-care tests until 2011, when policy restrictions to point-of-care HIV testing in Australia were removed2 and the Determine™ HIV Combo assay (Alere Pty Ltd, Sinnamon Park, Queensland, Australia), a fourth generation rapid test incorporating antibody and antigen components,3 was licensed in Australia by the Australian Therapeutic Goods Administration (TGA) for screening.4

The Determine™ HIV Combo test is licensed for screening only, and any reactive result requires confirmation by standard HIV tests at the laboratories.

Two other tests currently under consideration by the TGA are OraQuick® Advance HIV-1/2 Antibody Test and Uni-gold™ RHT.

The reason for the policy change in Australia is the number of people diagnosed with HIV is increasing each year, particular among gay and other men who have sex with men.

One of the key ways to reduce HIV transmission is to get people at risk tested early and frequently. However, data from surveys and clinics show that the uptake of testing is less than ideal in Australia.

Some community, clinical, research and government organisation in Australia are now offering HIV point-of-care tests to gay and other men who have sex with men in various settings: community organisation, clinics, and community events.

Although Australia has high quality HIV testing through laboratories, the availability of HIV rapid testing may overcome some of the known barriers to accessing HIV testing such as returning for a result, and the inconvenience of attending clinics,5 therefore resulting in more infections being diagnosed, and people receiving treatment sooner.

HIV point-of-care tests work best when they are used in populations where there is a high HIV prevalence such as in gay men and other men who have sex with men.

For example, based on data from the Sydney Rapid HIV Test Study6 using the Determine™ HIV Combo in a clinic population where 10,000 gay and other men who have sex with men are tested for HIV at current diagnosis rates there will be 100 reactive point-of care tests: of which 66% will be correct (the person does have HIV) and 34% will be incorrect (false positive).

In summary, for every two HIV infections detected, there will be one false positive point-of-care result.

HIV point-of-care tests: use in remote Australia?

The use of HIV point-of-care tests in a low HIV prevalence population such as remote Aboriginal and Torres Strait Islander communities with the Determine™ HIV Combo test will result in a very high number of falsepositives.

For example, if 10,000 HIV tests are conducted in remote Aboriginal communities in a year (or 100,000 in ten years), at current diagnosis rates7 there will may be three HIV infections diagnosed in ten years, but along the way, 600 false positive point-of-care results.

False positives in this setting will create unnecessary workload for health services, could erode confidence in the point-of-care test and potentially inflict harm on individuals and communities.

As any reactive point-of-care test needs to be confirmed by standard laboratory tests, patients in these remote settings may need to wait weeks to find out that in nearly all cases they do not have HIV.

Chlamydia and gonorrhoea point-of-care tests

Whilst lateral flow point-of-care tests for chlamydia and gonorrhoea have been available for a number of years, their widespread implementation has been constrained by their inaccuracy – meaning the tests will often miss cases of infection (poor sensitivity) but also result in false positive diagnoses (poor specificity) and also most are hard to do with too many steps.8 9 10 

However, a new test called GeneXpert® has become available, and recently received TGA approval, that uses molecular detection methods (much like the methods used in laboratory) within disposable cartridges and a self-contained instrument that provides point-of-care technology, albeit at a higher cost than lateral flow.

The GeneXpert® simultaneously tests for chlamydia and gonorrhoea. The GeneXpert® has been evaluated in Australian laboratories and field settings in Australia and the United States; evaluations have demonstrated that the test works as well as current laboratory tests.11 12

The technology will revolutionise point-of-care testing for chlamydia and gonorrhoea. The GeneXpert® can be used to test both urine and swab specimens and is easy to use.

Once urine or swabs have been collected from patients it takes about one minute to prepare the specimen (which is inserted into a test cartridge and put into the machine) which provides a result within 90 minutes.

The results appear on the computer screen as ‘Detected’ or ‘Not detected’ for each infection (chlamydia or gonorrhoea).

The same instrument (GeneXpert®) is recommended by the WHO for diagnosis of tuberculosis (TB), which affects millions of people globally, and in countries which have machines for TB there is the potential for the machines to be also utilised for testing for STIs.

Chlamydia and gonorrhoea point-of-care tests: use in remote Australia?

Currently, we are trialling the GeneXpert point-of-care test, developed by Cepheid, for both chlamydia and gonorrhoea detection in 12 remote communities in Western Australia, South Australia and Queensland.

This is the first use in the world of the GeneXpert® point-of-care test in routine clinical practice. The name of this randomised controlled trial with a crossover design is TTANGO (Test, Treat and Go).

What we are hoping to achieve is a reduction in transmission of chlamydia and gonorrhoea in the community and a reduction in repeat chlamydia and/or gonorrhoea reinfections.

Mathematical modelling has demonstrated such public health benefits are possible if we can give people access to tests results on the same day as their clinic visit, and if positive, they are given antibiotics immediately.13

The average time to treatment in many remote Aboriginal communities is 21 days (compared to three days in urban centres) and only 85% of people who tests positive receive treatment.14

The GeneXpert® point-of-care test has the potential to reduce the time to treatment to zero days, and increase treatment uptake to 100%.

Knowing the result of the test at the initial consultation could also improve the timeliness of partner notification.

Although not being measured in the TTANGO study, we would also expect to see a reduction in the short and longer term complications of untreated chlamydia and gonorrhoea infections15 which can include pelvic inflammatory disease, ectopic pregnancy and tubal factor infertility,16 17 and a range of adverse pregnancy and neonatal outcomes.18 19

Preparation for the TTANGO Trial has been underway for more than 18 months. This has included lengthy engagement with participating health services, laboratories, community and government organisations (see acknowledgements).

We have developed numerous standard operating procedures that are reflected in a training package for health professionals, and a range of support materials (e.g., training manual and posters that detail test procedures).

There has also been a strong focus on ‘quality management’ in TTANGO, to ensure that the high quality of testing that is routinely provided by laboratories is not compromised.

Routine laboratory testing will also be maintained during TTANGO, so that concordance of laboratory and GeneXpert® results can be monitored.

The implementation phase of the trial commenced mid 2013 and has gone smoothly. We will also be measuring acceptability of the GeneXpert® from both health centre staff and patient perspectives as well as the cost effectiveness of the tests during the trial.

A molecular point-of-care test for trichomoniasis has also recently been developed by Cepheid and as part of the TTANGO trial we are planning to evaluate its accuracy soon.

Syphilis point-of-care tests

Most commercially available syphilis point-of-care tests are lateral flow and detect treponemal antibody in blood, plasma or serum specimens.

In Australia, point-of-care syphilis tests that were commercially available prior to 2010 are TGA approved.

The syphilis point-of-care tests are relatively robust and unlike the chlamydia and gonorrhoea lateral flow point-of-care tests, they are easy to use with minimal training.

A drop of blood or serum is added to the test strip, followed by a few drops of test diluent, and results are available to be read in around 10–15 minutes.

The presence of a coloured test and control line on the test strip indicates a positive result. A number of evaluations in different settings have shown these tests to have good accuracy compared to standard laboratory treponemal reference tests.20, 21

A recent laboratory evaluation in Australia of some of these commercially available syphilis point-of-care tests demonstrated no difference in accuracy between HIV negative and positive people, but the tests tended to be slightly less accurate among early (primary) stage syphilis.22

Syphilis point-of-care tests are being increasingly widely implemented as part of screening policies in many countries, particularly in antenatal settings as part of the global strategy to eliminate maternal-to-child-transmission of syphilis (congenital syphilis), where resources and access to laboratory testing is limited and loss to follow up is frequent.23, 24

The major limitation of syphilis point-of-care tests is that most commercially available tests only detect treponemal antibody which remains elevated despite adequate treatment for syphilis.

As a result, in high prevalence settings the potential for overdiagnosis and overtreatment of syphilis, along with other sequelae including significant psychosocial consequences, is substantial.

A new point-of-care test (Chembio DPP® Screen and Confirm) is now available that can simultaneously detect both treponemal and nontreponemal syphilis antibodies as two separate test lines on the same test strip.

When interpreted together, a positive treponemal and non-treponemal test line suggests current syphilis infection, while a positive treponemal test line alone suggests past/treated infection.

This dual detection system may therefore be able to distinguish active from past treated infection and therefore reduce overdiagnosis and treatment in high prevalence settings, but further studies are required to validate the test in practice.

Syphilis point-of-care tests: use in remote Australia

Given the declining prevalence of syphilis in remote communities in Australia,25 the benefits of programmatic use of syphilis point-of-care tests in remote Australia are unlikely to be realised.

However, syphilis point-of-care tests may have a role as part of an outbreak response strategy to rapidly screen communities and provide immediate treatment to those with a positive result.

Results from treponemal only point-of-care tests could be cross checked with available medical records to confirm the positive point-of-care is the result of new, active infection rather than old treated infection, and thereby avoiding unnecessary treatment.

Conclusion

In summary, the use of STI point-of-care tests for chlamydia, gonorrhoea in remote Aboriginal and Torres Strait Islander communities is underway, and results will be available in the next few years on the potential benefits of the test in regards to improved service delivery and reduction in population infections rates, and also acceptability.

A test for trichomoniasis should also be a priority to help address the unacceptably high rates of this infection in remote communities.

The use of HIV point-of-care tests in remote settings will result in more harm than any benefit, but syphilis point-of-care tests may be useful in certain situations such as in response to outbreaks.

Acknowledgements

We thank the following organisations for their contribution to the TTANGO trial: participating health services, Queensland Aboriginal and Islander Health Council, Aboriginal Health Council of Western Australia, Aboriginal Health Council of South Australia, Apunipima Care York Health Council, Ngaanyatjarra Health Service, Queensland Health, West Australia Department of Health, West Australia Country Health Service, SA Health, Western Diagnostic Pathology, PathWest, Pathology Queensland, National Reference Laboratory, Cepheid, and Diagnostic Technology.

Test, Treat and Go (TTANGO) Investigators include Rebecca Guy, John Kaldor, Basil Donovan, David Wilson, Handan Wand, David Regan, Louise Causer and Steve Badman from the Kirby Institute, UNSW; James Ward,Baker IDI, Central Australia and Kirby Institute; Belinda Hengel from Apunipima Health Council; Lisa Natoli and David Anderson from the Burnet Institute; David Whiley from the Queensland Pediatric Infectious Diseases (QPID) Laboratory; Sepehr N Tabrizi from the Royal Women’s Hospital; Mark Shephard from Flinders University; Christopher Fairley from the University of Melbourne and Melbourne Sexual Health Centre; and Annie Tangey from Ngaanyatjarra Health Service. TTANGO is funded by Australian National Health and Medical Research Council project grant number 1009902.

Author notes

1 Baker IDI, Central Australia, Alice Springs, Australia;

2 The Kirby Institute, University of New South Wales, Sydney, Australia

3 The Burnet Institute, Melbourne, Australia.

 

References

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2 Ministerial Advisory Committee on AIDS Sexual Health and Hepatitis. (2011). National HIV Testing Policy: Commonwealth Government Department of Health and Ageing, 2011.

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4 Therapeutic Goods Administration. (2012, 17 December). Alere Determine HIV 1/2 Ag/Ab Combo test: information for consumers. Australian Government Department of Health and Ageing (DoHA). Retrieved from: www.tga.gov.au

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21 Jafari, Y., Peeling, R., Shivkumar, S., Claessens, C., Joseph, L., Pai, N. (2013). Are Treponema pallidum Specific Rapid and Point-of-Care Tests for Syphilis Accurate Enough for Screening in Resource Limited Settings? Evidence from a Meta-Analysis. PLoS One 8(2), e54695.

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25 Ward, J., Guy, R., Akre, S., Middleton, M., Giele, C., Su, J., et al. (2011). Epidemiology of syphilis in Australia: moving toward elimination of infectious syphilis from remote Aboriginal and Torres Strait Islander communities? Med J Aust, 194(10), 525–9.

 

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This page was published on 11 October, 2013

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