False-positive reactivity of fourth-generation HIV enzyme immunoassay caused by COVID-19 and other infections.

Background: Diagnosis of acute human immunodeficiency virus (HIV) infection and rapid initiation of antiretroviral therapy (ART) are the cornerstones in HIV elimination. Fourth- and fifth-generation HIV enzyme immunoassays (EIAs) can detect patients with acute infection. However, HIV false-positive results can occur, requiring confirmatory nucleic acid amplification testing, which is expensive and may not be available.

Objectives: This review highlights reports on various infections and vaccines causing false-positive reactivity in fourth-generation HIV immunoassays.

Results: Despite the improvements in tests of HIV immunoassays, false-positive results may occur, which require continuous updates in testing algorithms to be used appropriately with newer assays. Many factors can result in false-positive HIV serological assays, such as COVID-19, several viral, bacterial or parasitic infections, and vaccines.

Conclusions: Physicians should be aware of the causes of false-positive HIV reactions and include them in the clinical assessment of suspected cases and consider confirmatory testing.