Clinical and Laboratory Standards Institute guideline M53—Criteria for Laboratory Testing and Diagnosis of Human Immunodeficiency Virus Infection provides an extensive review of existing laboratory methods commonly used to test for HIV infection. The accurate diagnosis of HIV infection is essential for limiting the spread of infection and for the appropriate clinical management of persons infected with HIV. Numerous tests and strategies have been developed and are used by laboratorians and clinicians to diagnose HIV infection. This guideline also offers recommendations for how to best use and interpret these tests accurately and effectively to diagnose HIV infection.

This guideline replaces the previous edition of the approved guideline, M53-A, published in 2011. Several changes were made in this edition, including: • Reorganizing the text to follow the testing path of workflow • Expanding the scope to include testing recommendations for resource-limited settings and for managing patients with HIV type 1-positive infections • Adding an HIV testing and interpretation process flow chart • Revising the algorithms used to select HIV testing protocols and associated text • Deleting all references to HIV test “generations” • Updating: ? Information on currently available and preferred HIV tests ? Test principal figures ? Information on molecular testing ? Recommended approaches for HIV diagnostic testing ? Special situations for HIV testing ? QC information

This guideline provides: • An overview of the natural history and response to HIV infection • An in-depth review of initial and supplemental tests used for diagnosing HIV infection • Tests for monitoring and managing HIV type 1 (HIV-1) infections • Recommendations for initiating an HIV QC program This guideline also discusses special situations that commonly cause confusion in HIV testing, including: • Diagnosis of acute and recent HIV infection • Testing for HIV-1, group 1, non-B subtype, and HIV type 2 (HIV-2) infections • Initial and supplemental testing during pregnancy, labor, and delivery • Newborn testing • HIV-1 seroconversion or incomplete antibody (Ab) response • Recipients of HIV vaccines or chimeric antigen receptor T-cell (CAR-T) therapy • Viral suppressors (elite controllers [ECs]) • Testing for pre- and postexposure prophylaxis • Testing for CSF for HIV-associated central nervous system (CNS) disorders • Self-collection and self-testing Also included are: • Diagnostic testing algorithms to assist clinicians and laboratorians in the stepwise use of HIV tests • A framework for determining the need for additional testing • Results interpretation • Reporting criteria for commonly obtained test results This guideline is intended for use in diagnosing HIV-1 and HIV-2 infections in both advanced diagnostic laboratories and point-of-care (POC) settings, including resource-limited environments. It does not: • Discuss methods or strategies for screening the blood supply or organ or tissue donation. • Provide recommendations for use outside the clinical setting. • Cover issues for diagnosing HIV from nonhuman material, environmental surfaces, or postmortem samples.