Why are extra tests required to confirm an HIV diagnosis?

Our laboratory uses a 4th generation HIV test to detect both antibodies to HIV-1 and HIV-2, as well as the p24 antigen. This is a highly sensitive test with a reduced window period post-exposure so individuals can receive a diagnosis as early as possible after a possible exposure. However, this test is only the first screening test recommended by the CDC for HIV diagnosis.

Non-reactive results from a 4th generation HIV test indicate a negative result and do not require any additional tests, unless an acute infection (very recent exposure) is suspected. In that case, an HIV nucleic acid test may be required. 

Reactive results from a 4th generation HIV test must be then tested with an HIV-1 / HIV-2 antibody differentiation immunoassay:

• Reactive results from an antibody differentiation immunoassay confirm an HIV diagnosis.
• Non-reactive results in an antibody differentiation immunoassay should be tested with an HIV-1 nucleic acid test. 
  • If reactive in the nucleic acid test (and reactive in the 4th generation screen and non-reactive in the differentiation immunoassay), it indicates an acute HIV-1 infection.
  • If negative in the nucleic acid test (and reactive in the 4th generation screen and non-reactive in the differentiation immunoassay), it indicates a false-positive result in the initial 4th generation screen; hence the individual is negative for HIV.