HIV testing overview
In the UK, current approaches to HIV testing are to make it a normal rather than exceptional medical event, for it to be offered in a wide range of settings, and to use newer technologies that are more effective in identifying recent infections than previous techniques.
For many years, the majority of HIV diagnostic tests looked for HIV antibodies only. One or two weeks after initial exposure to HIV, antibodies to HIV antigens begin to appear in the blood, as a result of the immune system’s defence against infections . These antibodies persist for life, providing distinctive markers which can be identified by screening tests.
Most HIV antibody tests are in an ELISA or EIA format (enzyme-linked immunosorbent assay). The first generation of ELISA tests for HIV antibodies were introduced in 1985, and third-generation ELISAs are still widely used in a number of countries.
The accuracy of third-generation ELISAs (i.e. their sensitivity and specificity) is excellent. However they are less good at detecting primary infection than fourth-generation tests, so their use is no longer recommended in the UK and a number of other countries.
Fourth-generation ELISAs test for both HIV antibodies and p24 antigen. High levels of p24 are present in the blood of newly infected individuals during the short period between infection and seroconversion, making p24 antigen assays useful in diagnosing primary HIV infection.
The window period of a fourth-generation test is approximately five days shorter than that of a third-generation test. The ‘window period’ refers to the period after infection during which markers of infection (antibodies, antigen) are absent or too scarce to be detectable.
The duration of the window period varies between individuals. Moreover, different authorities give slightly different estimates for its length, but when a fourth-generation test is used, it is usually considered to be somewhere between two and four weeks.
Fourth-generation tests are extremely accurate - an evaluation of ten tests found that all except one had a sensitivity of 100% (in other words, all HIV-positive people tested were correctly diagnosed). Moreover, all had a specificity of 99.7% or over (in other words, if 1000 HIV-negative people were tested, 997 would be correctly diagnosed as such).
HIV RNA tests (viral load tests) are primarily used to monitor disease progression, and are only licensed for this purpose. However they can also help diagnose primary infection, and are sometimes used for screening in the United States and elsewhere. The tests’ window periods are short, but false positives are fairly common.
The tests described so far all require a blood sample, usually taken from a vein in the arm. (Antibody testing of urine is possible, but rarely used.) However rapid tests are available, which require the less invasive samples of finger-prick blood or ‘saliva’ (in fact, oral fluid from around the gums).
Rapid tests are often referred to as point-of-care tests because rather than sending a blood sample to a laboratory, the test can be conducted and the result read in a doctor’s office or a community setting, without specialised laboratory equipment.
The result can usually be given within 20 or 30 minutes.
Almost all rapid tests look for HIV antibodies only. However a combined antibody / p24 antigen rapid test was introduced in 2009 (Determine HIV-1/2 Ag/Ab Combo).
However, some laboratory professionals have viewed these tests with scepticism, noting inferior performance to fourth-generation tests and raising concerns about how quality control can be maintained away from the lab. While a number of tests have sensitivities and specificities of 99% or above, comparison evaluations of different rapid tests often show a wide range in performance, with some tests being much less sensitive and specific. Moreover, window periods tend to be a few days longer than for equivalent laboratory tests.
In addition, rapid tests that use saliva rather than blood may be subject to more sampling variation, influencing the accuracy of the test.
For more information on the accuracy of rapid tests, see NAM’s publication HIV Transmission and Testing.
