Human Immunodeficiency Virus Diagnostic Testing: 30 Years of Evolution

Abstract

A concern during the early AIDS epidemic was the lack of a test to identify individuals who carried the virus. The first HIV antibody test, developed in 1985, was designed to screen blood products, not to diagnose AIDS. The first-generation assays detected IgG antibody and became positive 6 to 12 weeks postinfection. False-positive results occurred; thus, a two-test algorithm was developed using a Western blot or immunofluorescence test as a confirmatory procedure. The second-generation HIV test added recombinant antigens, and the third-generation HIV tests included IgM detection, reducing the test-negative window to approximately 3 weeks postinfection. Fourth- and fifth-generation HIV assays added p24 antigen detection to the screening assay, reducing the test-negative window to 11 to 14 days. A new algorithm addressed the fourth-generation assay's ability to detect both antibody and antigen and yet not differentiate between them. The fifth-generation HIV assay provides separate antigen and antibody results and will require yet another algorithm. HIV infection may now be detected approximately 2 weeks postexposure, with a reduced number of false-positive results.

FIG 1

Centers for Disease Control/Food and Drug Administration algorithm for second-generation HIV tests (20). †, an immunofluorescence assay (IFA) for HIV-1 antibodies has recently been licensed by the Food and Drug Administration and can be used instead of the Western blot assay. Positive and negative IFA results should be interpreted in the same manner as similar results from Western blot tests. An indeterminate IFA result should first be tested by HIV-1 Western blot assay and then as indicated by the Western blot test results. §, perform HIV-2 EIA only if there is an identified risk factor for HIV-2 infection.

FIG 2

CDC algorithm for use with a fourth-generation HIV antibody/antigen screening test (21).

FIG 3

Schematic representation of the 30-year evolution of HIV diagnostic assays.