This policy covers laboratory-based testing and non-laboratory-based testing. The TGA has produced guidance to assist and inform its evaluation of HIV tests:
TGA Clinical Performance Requirements and Risk Mitigation Strategies for HIV Tests
This guidance sets out differential performance requirements for laboratory tests, HIV point-of-care tests and HIV self-tests. It recognises that a lower performance threshold may be acceptable in a test which is part of a screening protocol requiring confirmatory testing, and that confirmatory testing must be able to demonstrate the highest quality and performance. It also specifies the need for training. It is essential that those using any test are familiar with its limitations and can communicate these limitations to the person being tested or, in the case of a self-test, that the package insert addresses these limitations.
This TGA guidance document is prospective and relates to any tests which may be submitted to the TGA for evaluation.
As with most infectious diseases, the human body responds to HIV infection by producing antibodies in an expected manner. These antibodies are usually produced within several weeks after infection, although in rare cases they may not be detected for a number of months. Immediately after infection has occurred it is not possible to detect any markers of infection. This period of time generally lasts for about 10 days after infection and is referred to as the ‘eclipse period’. Currently, the first marker that is detected following the eclipse period is viral nucleic acid (RNA or proviral DNA) or p24 antigen if nucleic tests are not used. HIV antibodies are generally detected within 4 weeks, but this depends on the type of tests used including HIV point-of-care tests (rapid HIV tests) where detection of antibodies may take longer.
In Australia, most laboratories use 4th generation HIV antibody/antigen screening tests and the time to detection is generally 3-4 weeks from infection; however rare outliers have been reported. Following a possible exposure to HIV, it is important to provide certainty around clinical information regarding a person’s infection status, so statistical confidence limits (99%) are applied to the average time that standard screening tests become detectable to declare a person is uninfected. This period is typically set at 12 weeks. Therefore, a clinician can say with confidence that a person with a negative HIV antibody test has not acquired HIV infection after 12 weeks, provided there has not been any further risk exposure. This approach considers all antibody-based tests including rapid HIV tests, where longer seroconversion periods have been observed.
Reference laboratories perform a range of laboratory-based testing strategies that will detect and confirm HIV infection earlier than 12 weeks, so it is reasonable for such laboratories applying testing strategies that contain 4th generation (antigen containing) and nucleic acid tests that the window period may be reported as 6 weeks.
Laboratories are subject to requirements established by the NPAAC. Laboratory staff are also subject to professional standards established by the RCPA and international standards under which laboratories receive NATA/RCPA accreditation.
Most point-of-care tests require longer window periods to detect an infection compared to laboratory-based tests (immunoassays and nucleic acid detection). In this policy, reference to point-of-care tests refers to rapid HIV tests being used at point of care. Australian evaluations of point-of-care tests have shown that many acute (very recent) infections would not be detected if point-of-care tests alone were used among people from high HIV incidence populations, such as gay and bisexual men.8,9
In addition to the guidance on performance requirements issued by the TGA, point-of-care HIV testing services are additionally subject to requirements established by the jurisdictions and health-care workers performing point-of-care tests. Additionally, jurisdictions may require those performing HIV point-of-care tests to contribute to surveillance data collection. Examples of these additional requirements include:
- The NSW Framework and Standard Operating Procedure for HIV Point of Care Testing
- The NRL Requirements for Participation in a specific External Quality Assessment Scheme (EQAS)
- The Royal Australian College of Pathologists External Quality Assurance Program
Sites that perform point-of-care testing should be enrolled and actively participate in a relevant external quality assurance program. It is recommended that the site contribute to jurisdictional or national data collection.
The application of these requirements is the responsibility of the director of any service which provides HIV testing. The TGA requires that an appropriately trained health-care worker is responsible for performing or supervising all aspects of the testing process from sample collection to test interpretation. All staff, including voluntary service providers, who perform HIV point-of-care testing should be able to demonstrate competency in the performance of the tasks for which they are responsible. Training should cover test operation, sample collection and interpretation as well as issues of consent, conveying the result, and any confirmatory testing processes.
Staff should also receive specific training on the operation of any newly introduced point-of-care test or sample collection process being used in a facility.
Services providing point-of-care testing should have a clear linkage to clinical and pathology services for the conduct of confirmatory testing. This includes when point-of-care testing is performed in community-based testing services and in outreach settings, such as a mobile clinic or pop-up site.
HIV self-testing involves a person collecting their own specimen (e.g. blood from a finger prick) for HIV testing, applying it to a testing kit or device and interpreting the test result. Currently, there are no devices allowing for oral fluid self-testing approved by the TGA for supply in Australia. Self-testing for HIV provides opportunities for improving access to testing and increasing frequency of testing among people at risk of HIV infection. Self-testing minimises the barriers associated with conventional testing e.g. the need to attend a health service to access a test, time taken for test results to be available, poor access to health-care providers, feelings of stigma associated with testing, and the risk of discrimination.10 Self-testing can also support autonomy, and provide added confidentiality, privacy and convenience for people who may not otherwise engage in HIV testing. It has been shown in multiple studies, including in Australia, to be highly acceptable and easy to use with little to no support from trained staff.10,11 A randomised controlled trial among Australian gay and bisexual men attending sexual health services showed that the provision of HIV self-testing increased the uptake and frequency of HIV testing, without diminishing the frequency of sexual health screening at services.11
To maximise the potential benefits of self-testing devices, the instructions for use (the package insert) must be sufficiently illustrative and comprehensible so that a user can perform the test correctly and interpret the result accurately. In addition, the package insert must explain sensitivity and specificity limitations including the predictive value when used in high- and low-prevalence populations, the window period, the need for confirmatory testing, and referral points.
In 2018, the first self-testing device was approved by the TGA. This device allowed self-testing to be performed in the absence of a health-care provider or trained operator. Requirements for the online supply of the first HIV self-test were that the sponsor
provide an online instructional video for users to view prior to using the test, provision of an HIV telephone helpline providing 24-hour customer support, training in the correct use of the device and interpretation of results, and information about how to access psychosocial support in the event of a reactive result. Additionally, where the sponsor supplies the test for use by healthcare workers (in organisations that employ health professionals (e.g. medical practitioners, registered nurses) to perform or supervise6 the performance of testing by appropriately trained staff)7, those healthcare workers must have received training in the delivery and administration of HIV testing in accordance with the requirements of this Policy, and organisations must have an established relationship (in relation to the referral and testing of specimens) with a NATA-accredited
medical testing laboratory.
Before their availability in Australia, any new testing technology or sample collection device must be approved by the TGA. Currently, there is no TGA-approved HIV test that is intended for use with self-collected samples, such as oral fluid or dried blood spots. However, there are various provisions for exemption, such as for a clinical trial, that allow for regulated access to unapproved devices.
Self-sampling is when a person collects their own biological sample for HIV testing (e.g. oral fluid or blood from a finger prick) and after collection sends it to a laboratory for testing. Unlike HIV point-of-care testing and self-testing, the analysis of a self-collected sample is performed in the laboratory and a confirmed result is obtained. Dried blood spot sampling for HIV and hepatitis C testing has been successfully used in a government-led pilot study in New South Wales since 2016.12 The study is being conducted under a clinical trial exemption from the TGA.
Self-sampling for HIV testing may provide opportunities for improving access to testing and increasing frequency of testing among people at risk of HIV infection through minimising the barriers associated with conventional testing e.g. the need to attend a health service to access a test, poor access to health-care providers, stigma, poor venous access, and the risk of discrimination. Self-sampling can also support autonomy, and provide added confidentiality, privacy and convenience for people who may not otherwise engage in HIV testing. International research suggests self-sampling for HIV is highly acceptable and easy to use with little to no support from trained staff, although return rates for self-sampling kits may vary.13,14