Management of Discordant HIV Test Results

Understanding the Discordant Results

The Centers for Disease Control and Prevention recommends that when a patient has a reactive OraQuick HIV test but a non-reactive 4th generation test, the next step is to perform a nucleic acid amplification test (NAAT) such as HIV RNA testing to rule out acute HIV infection 1
4th generation tests detect both HIV antibodies and p24 antigen, allowing for earlier detection of infection than antibody-only tests, with the American College of Physicians noting the importance of understanding the differences in test sensitivity and specificity 2
The discordant pattern of a reactive OraQuick result and a non-reactive 4th generation test suggests several possibilities, including a false-positive OraQuick result, very early HIV infection, or technical error in one of the tests, as reported by the Clinical Infectious Diseases journal 3

The Centers for Disease Control and Prevention recommends performing HIV RNA testing immediately to rule out acute infection, as HIV RNA can detect infection before antibody or antigen tests become positive 1
If HIV RNA is negative, the OraQuick result is likely a false positive, and the patient should be informed that they are likely HIV-negative, according to the MMWR Recommendations and Reports 4
If HIV RNA is positive, HIV infection should be confirmed and appropriate management initiated, including ordering additional tests such as CD4 count, viral load quantification, and resistance testing, as recommended by the American Academy of HIV Medicine 2

For patients with recent high-risk exposure, post-exposure prophylaxis should be considered while awaiting definitive results, as recommended by the American Family Physician 5
For patients with ongoing risk factors, Pre-Exposure Prophylaxis (PrEP) should be considered once HIV infection is definitively ruled out, according to the JAMA journal 6

If initial HIV RNA testing is negative, repeat testing in 4 weeks is recommended to definitively rule out infection, as reported by the Clinical Infectious Diseases journal 3
For high-risk individuals, additional serologic testing at 6, 12, and 24 weeks may be warranted, according to the Clinical Infectious Diseases journal 3
All test results should be documented clearly in the patient's medical record, as recommended by the MMWR Recommendations and Reports 7

In individuals without recognized epidemiologic risk factors, a reactive initial HIV screening test followed by a same‑day negative confirmatory test should be interpreted as indicating that the patient is likely HIV‑negative; they can be considered uninfected pending further follow‑up. 8

When a Western blot or other confirmatory assay yields an indeterminate result, perform an HIV‑2 enzyme immunoassay (EIA) to evaluate for infection with HIV‑2. 8
If the indeterminate result persists, repeat the confirmatory testing at 6 months to definitively rule out infection. 8

For persons originating from regions where HIV‑2 is endemic—or for their sexual partners—supplementary HIV‑2 testing should be performed if the HIV‑2 EIA is repeatedly reactive while the HIV‑1 Western blot is negative or indeterminate; the specimen should be sent to the state public health laboratory for confirmatory HIV‑2 assays. 8