Fourth-generation tests

Fourth-generation tests, introduced in the late 1990s, are ELISAs which test for both HIV antibodies and p24 antigen. It is essentially a third-generation ELISA, to which is added an ELISA for p24 antigen.

They may also be called combined antigen/antibody tests. In product names, 'Ag/Ab' indicates that the test looks for both antigen and antibody.

Testing for p24 detects some cases of HIV infection before antibodies are produced, shortening the window period in which people may test negative despite having infection.

Not all tests distinguish between samples that are positive for antibody and samples that are positive for p24. Therefore, although they may help identify people with primary infection, they do not distinguish between primary and chronic infection.

Fourth-generation tests are recommended for use as a first-line assay in the UK guidelines.^1,2 Most commercially available tests are able to detect HIV-2 and diverse HIV-1 strains such as subtype O.

Blood samples are normally used, although some kits can also be used with saliva.

These tests are less commonly used in the United States and, so far, none have been FDA approved.³

Like any screening test, a reactive (positive) result will be confirmed with one or two supplementary tests.