Does a patient with a positive rapid Human Immunodeficiency Virus (HIV) test but a negative HIV antibody (Ab) confirmation test have HIV?

HIV Status Interpretation: Positive Rapid Test with Negative Confirmatory Antibody Test

A patient with a positive rapid HIV test but negative HIV antibody confirmation test should NOT be diagnosed with HIV infection and should be considered uninfected in the absence of epidemiologic risk factors. 1

Diagnostic Algorithm

Initial Interpretation

• If the HIV-1 Western blot is negative and HIV-2 EIA is not repeatedly reactive, the specimen should be considered negative for HIV antibodies. 1
• The patient should be informed that test results for HIV infection are negative. 1
• In the absence of recognized epidemiologic risk factors, the patient should be considered uninfected with HIV and counseled accordingly. 1

Critical Caveat: Acute HIV Infection Window Period

• If the confirmatory testing is negative or indeterminate, follow-up testing on a blood specimen collected 4 weeks after the initial reactive test should be performed, especially if risk factors are present. 1, 2, 3
• Persons should be counseled to follow risk-reduction guidelines during the intervening period. 1
• For high-risk individuals, additional serologic testing at 6,12, and 24 weeks is recommended due to the window period. 3
• An HIV RNA assay may be helpful in excluding acute HIV infection in high-incidence populations with recent exposure. 3

Special Clinical Scenarios

Pregnant Women Requiring Immediate Decision

• For women in labor with a positive rapid HIV test, antiretroviral prophylaxis should be administered to mother and newborn based on the positive rapid test without waiting for confirmatory results. 1
• If confirmatory test results are negative, prophylaxis should be stopped and breastfeeding may be initiated. 1
• Assistance with hand and pump expression to stimulate milk production should be offered given the possibility of negative confirmation. 1

Repeat Confirmatory Testing Importance

• Research demonstrates that among persons with discordant results (positive rapid, negative/indeterminate confirmation), approximately 19% were ultimately confirmed HIV-infected when repeat testing was performed. 4
• Weakly reactive rapid test results are significantly more likely to be false positives compared to strongly reactive results. 5
• The false-positive rate of the two-test rapid algorithm can be as high as 10.5%, dropping to 3.3% when only strong-positive rapid results are considered. 5

Key Clinical Pitfalls

Never Initiate Treatment Without Confirmation

• Treatment for HIV should never be initiated until infection has been documented with confirmatory testing. 2, 3
• All positive screening tests must be confirmed by Western blot or indirect immunofluorescence assay before establishing a definitive HIV diagnosis. 2

Specimen Type Matters

• Confirmatory testing following a reactive rapid test should be conducted using serum or plasma when possible, as oral fluid Western blots have lower sensitivity. 4
• Factors associated with true HIV infection in discordant cases include having an initial indeterminate Western blot (versus negative) and having an initial oral fluid Western blot (versus serum). 4

False-Positive Considerations

• The most probable causes of false-positive rapid test results are serological cross-reactivity or non-specific immune reactivity. 5
• In population-based surveys, most HIV-infected adults with discordant rapid tests were virally suppressed without antiretroviral drugs, representing elite controllers or long-term non-progressors. 6

Recommended Testing Sequence

1. Send confirmatory testing immediately (Western blot or indirect immunofluorescence assay). 2, 3
2. If negative confirmation: Consider patient uninfected unless high-risk exposure within past 4-6 weeks. 1
3. If acute infection suspected: Order HIV RNA assay to exclude window period infection. 3
4. If indeterminate confirmation: Perform HIV-2 EIA testing and follow-up testing at 4 weeks, then 6 months if still indeterminate. 1, 3
5. Counsel on risk reduction during the follow-up period regardless of initial interpretation. 1