Why do false reactive (positive) test results occur?

Why do false reactive (positive) test results occur?

The reason that an HIV-negative person may have an initial HIV false reactive test result could be due to the use of a highly sensitive rapid diagnostic test as the first test within a national testing algorithm. This is why an HIV positive diagnosis cannot be made following a single test. False reactive (positive) test results can also occur due to a degree of cross-reactivity with other pathogens such as schistosomiasis or trypanosomiasis (African sleeping sickness). Specificity of HIV assays is also known to vary greatly because of other endogenous factors and these vary greatly in different geographical regions.
Positive predictive value is calculated:

๐‘๐‘Ÿ๐‘’๐‘ฃ๐‘Ž๐‘™๐‘’๐‘›๐‘๐‘’ ร—๐‘ ๐‘’๐‘›๐‘ ๐‘–๐‘ก๐‘–๐‘ฃ๐‘–๐‘ก๐‘ฆรท ๐‘๐‘Ÿ๐‘’๐‘ฃ๐‘Ž๐‘™๐‘’๐‘›๐‘๐‘’ ร—๐‘ ๐‘’๐‘›๐‘ ๐‘–๐‘ก๐‘–๐‘ฃ๐‘–๐‘ก๐‘ฆ+ (1โˆ’๐‘๐‘Ÿ๐‘’๐‘ฃ๐‘Ž๐‘™๐‘’๐‘›๐‘๐‘’)ร—(1โˆ’๐‘ ๐‘๐‘’๐‘๐‘–๐‘“๐‘–๐‘๐‘–๐‘ก๐‘ฆ)
For prevalence of 1%, sensitivity 99%, specificity 98% PPV =(0.01ร—0.99)รท(0.01ร—0.99)+((1โˆ’0.01)ร—(1โˆ’ 0.98))

It is also important to note that the positive predictive value of all HIV tests will be lower when the HIV prevalence in the population is lower. This means that even if a test has a sensitivity of โ‰ฅ99% and a specificity โ‰ฅ98% (as specified in WHO pre-qualified diagnostics criteria for the performance of HIV serology assays www.who.int/diagnostics_laboratory/procurement/purchase/en/) in a low prevalence setting of 1%, the positive predictive value (the probability of a positive test being truly positive) if only one test is used, is always low (33.3%). Therefore when only one test is used, the probability of a positive test result being false is high.

WHO therefore recommends that countries use at least two different testing strategies according to the HIV prevalence in the population being tested. In a high (โ‰ฅ5%) HIV prevalence population, two sequential positive (reactive) test results, and in a low (<5%) HIV prevalence population three sequential positive (reactive) test results, are needed to provide a person with an HIV-positive diagnosis.

If there is discordance in the results โ€“ for example, in a setting with high (โ‰ฅ5%) HIV prevalence where Assay 1 is reactive (A1+), Assay 2 is non-reactive (A2-), and assay 3 is reactive (A3+), or in a setting with low (<5%) HIV prevalence where A1+, A2+, A3- โ€“ then the status is HIV-inconclusive and the person should return for re-testing after two weeks following the same approach as above.

Using the WHO testing strategies with a validated national testing algorithm where rapid diagnostic tests are used in series will provide a correct diagnosis in 99.9% of cases.

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