CLSI M53-P provides an overview of the natural history and response to HIV infection, and in-depth review of initial and supplemental tests for the diagnosis of HIV infection and initiation of a quality control (QC) program for HIV testing. This guideline also addresses special situations that commonly confound HIV testing, including the diagnosis of acute and recent HIV infection, initial and supplemental testing for HIV-1, nonclade B, and HIV-2 testing. In addition, diagnostic testing algorithms are provided to assist clinicians and laboratorians in the step-wise use of these tests, as well as a framework for additional testing and the interpretation of results. Futhermore, reporting criteria for commonly obtained test results are also provided.