When an HIV infection is suspected, it is most commonly diagnosed by tests that can detect the presence of HIV antibodies and/or antigens in either the blood or saliva. An antibody is a type of protein secreted by white blood cells that can detect and destroy foreign bodies like viruses or bacteria. An antigen, by contrast, is any substance that can provoke an immune response in the form of antibodies (as happens with HIV).
The tests used to confirm HIV infection are designed to react in the presence of these agents. A "positive" result means that HIV antibodies/antigens have been detected and that an infection has occurred. A "negative" result means that no antibodies/antigens have been detected and that HIV infection has not occurred.
Conversely, a "false positive" is when a test incorrectly indicates an HIV infection, while a "false negative" is when the test incorrectly shows that no infection has occurred. Both of these are relatively rare are using current testing assays.
Understanding the "Window Period"
People will usually develop measurable levels of HIV antibodies within 30 days of infection, although some may take longer—up to three months in some cases. HIV antigens, by contrast, take between between two to five weeks to develop.
Before this happens, there is a period wherein antibody/antigen levels are too low to be reliably detected. This is called the "window period." It is during this time that an infected person can pass HIV to others, but still have a negative result if given an HIV test.
If you believe you have been infected and suspect when you might have been accidentally exposed to HIV, it's important that you share this with your doctor or testing center. They can then help determine if the HIV test falls within the window period or if it can be performed with reasonable level of reliability.
HIV Antibody Tests: ELISA and Western Blot
The HIV ELISA ("enzyme-linked immunosorbent assay") is a highly sensitive test that changes color in the presence of HIV antibodies. Results are assigned a numeric value, with values below 1.0 indicating a negative result and values above 1.0 indicating a positive (or reactive) result. Although the ELISA offers a high probability for HIV infection, it is not used alone as in the detection of HIV.
When an ELISA test produces a positive result, a second antibody test, called the Western Blot, is used to confirm the results. Together, the ELISA and Western Blot are shown to have an accuracy of 99.9% in the general U.S. population, with a false-positive rate of about one out of every 250,000 tests performed.
Occasionally, the tests can return with an indeterminate or inconclusive result. This can happen for a number of reasons:
- The infection may have been too recent to reliably detect.
- There may have been problems with the test sample or the testing procedure itself.
- Acute infections like syphilis or Lyme's disease can sometimes elicit a false positive result, as can autoimmune conditions like lupus or diabetes.
If a person has an inconclusive result, the tests should be repeated.
Combination HIV Antigen/Antibody Tests
On June 27, 2014, the U.S. Centers for Disease Control and Prevention (CDC) recommended a new strategy for HIV testing using 4th generation combination assays able to detect HIV infection up to four weeks earlier than ELISA/Western Blot assays.
Currently there are two such tests approved for use by the U.S. Food and Drug Administration (FDA): the Alere Determine HIV 1/2 Ag/Ab Combo and the Abbott ARCHITECT HIV Ag/Ab Combo. Rather than relying solely on the detection of HIV antibodies, these combination assays are able to detect both HIV antibodies and antigens.
The CDC recommends a three-step approach to HIV testing:
- Conduct initial testing with Ag/Ab combo assays. If the result is negative, then no further testing is needed.
- If the first result is positive, conduct a second test to differentiate HIV-1 and HIV-2 antibodies, a step considered important in determining the course of therapy for the HIV-infected individual.
- If the second result is negative, a third test (called the HIV-1 NAT) would be performed to differentiate acute HIV-1 infection from an initial false positive result. The HIV-1 NAT is able to detect small quantities of viral RNA is as little as 1-2 weeks.
Due to the high reliability of the three-step approach, confirmation by way of a Western Blot is no longer considered necessary.
Rapid In-Home HIV Tests
Rapid in-home HIV tests are ELISA-based assays that can deliver results in as a little as 20 minutes (as opposed to standard ELISA/Western Blot assays that can take several days). The tests are performed using saliva samples, the results of which can either either "negative" or "preliminary positive." Preliminary positives must be confirmed with a Western Blot performed in a lab.
In 2012, the FDA approved the first in-home rapid HIV test for direct sale to consumers. While the products are reasy to use and offer linkage to care for those who do test positive (via a 24-hour consumer hotline), some are concerned that the lack of face-to-face counseling and potential breaches in informed consent may undermine prevention efforts.
Furthermore, while the in-home tests offer the same sensitivity and specificity as a point-of-care tests, clinical research has demonstrated a false-negative rate of around 7%—or roughly one out of 12 tests.
Another study published by the University of California, San Francisco has suggested that fourth generation rapid tests have a "real life" accuracy of about 86% in correctly identifying HIV-positive cases, but only 54% accuracy in confirming serostatus during the early, acute stages of HIV infection.
With mounting evidence suggesting that early diagnosis and treatment may prevent a number of long-term complications—including a possible reduction in the viral reservoirs where HIV can persist for decades—the need for accurate identification during acute infection is considered imperative.
Chou, R.; Huffman, L.; Fu, R.; et al. "Screening for HIV: a review of the evidence for the U.S. Preventive Services Task Force." Annual Internal Medicine. July 2005; 143(1):55-73.
U.S. Food and Drug Administration (FDA). "First Rapid Home-Use HIV Kit Approved for Self-Testing." FDA Consumer Health Information. Silver Spring, MD; July 2012. Document: UCM311690.
Greenwald, J.; Burstein, G.; Pincus, J.; et al. "A Rapid Review of Rapid HIV Antibody Tests." Current Infectious Disease Reports. March 2006; 8(2):125-131.
Pilcher, C.; Louie, B.; Facente, S.; et al. "Performance of Rapid Point-of-Care and Laboratory Tests for Acute and Established HIV Infection in San Francisco." PLOS | One. December 12, 2013; DOI: 10.1371/journal.pone.0080629.
Branson, B.; Owen, S.; Wesolowski, M.; et al. "Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations." U.S. Centers for Disease Control and Prevention (CDC). Atlanta, Georgia; released June 27, 2014.