Rapid Diagnostic Testing for HIV:
Clinical Implications of a New Diagnostic Tool

RAPID DIAGNOSTIC HIV TESTS

Rapid HIV tests to detect HIV antibody are designed to allow health care providers to supply definitive negative and preliminary positive results in a few minutes at the time of an initial patient visit. In comparison, traditional enzyme immunoassays (EIAs) operate with a paradigm that requires specimen transmittal to a laboratory, the creation of batches of specimens for efficient, cost-effective processing, the use of expensive, semi-automated or automated equipment, and the presence of significant operator expertise to perform properly and reliably. These requirements often delay results from reaching the patient for as much as 1-2 weeks.²² Rapid HIV tests are comparable in sensitivity and specificity to traditional EIAs, but can be performed by testing personnel with limited technical expertise in as little as 10 minutes.

A number of HIV tests are being used worldwide. In the United States, six rapid HIV tests have received FDA approval:

• The Single Use Diagnostic System for HIV-1 (SUDS, Abbott Laboratories, Abbott Park, IL – no longer marketed),
• OraQuick® HIV-1 (OraSure Technologies, Bethlehem, PA),
• OraQuick®Advance HIV-1/HIV-2 (OraSure Technologies, Bethlehem, PA),
• Reveal™ (MedMira Laboratories, Halifax, Nova Scotia),
• Uni-Gold™ Recombigen® HIV (Trinity Biotech plc (Wicklow, Ireland), and
• Multispot HIV-1/HIV-2 (Bio-Rad Laboratories, Hercules, CA).

Additional rapid HIV tests are under FDA consideration. Many of the candidate rapid HIV tests are designed for use with a variety of specimen samples, including: serum, whole blood, plasma and/or oral mucosal transudate (OMT). Using whole blood, the five FDA-currently available FDA-approved rapid HIV tests have sensitivities ranging from 95.3% to 100% and specificities ranging from 96.7% to 100%. Performance results of six commercially available rapid HIV tests, using plasma as the test specimen, demonstrate sensitivities ranging from 96.7% to 100% and specificities ranging from 98.5% to 100%.⁹

The sensitivity and specificity of most rapid assays are comparable to those of non-rapid EIAs. In low prevalence settings, the predictive value of a single rapid HIV negative test result is very high. Hence, a negative rapid HIV test does not require further testing, and negative results with result-specific counseling can be provided to most people at the time of their initial visit. However, because the positive predictive value varies with prevalence of HIV infection in the population tested, the positive predictive value will be low in populations with low prevelance.²³ This phenomenon has led to a testing strategy that requires a reactive EIA or rapid HIV test to be confirmed by a second, independent supplemental test.²⁴ In studies conducted outside the United States, specific combinations of two or more different rapid HIV assays have provided results as reliable as those from the EIA/western blot combination that is currently in widespread use.²⁵ In the Unites States, current recommendations require confirmatory testing to be conducted utilizing a Western blot or an immunofluoresence assay.²⁶

The “window” of HIV diagnosis is dependent upon the diagnostic approach utilized to detect its presence. Following exposure, entry of the HIV virus into the bloodstream typically occurs within 3 to 7 days, while detectable HIV-1 RNA can be demonstrated 7 to 14 days later. A detectable p24 antigen may be present between 12 to19 days, but antibody seroconversion and detection occurs between 30 to 60 days post-exposure. The onset of symptoms typically occurs 3 to 4 weeks post-exposure and most patients are symptomatic with a flu-like illness at the time of antibody seroconversion.

The ease of performing some rapid HIV tests led their manufacturers to seek and be granted waived test status under the federal Clinical Laboratory Improvement Amendments (CLIA). However, in order to ensure a high-quality testing environment, the FDA has limited the test to registered laboratories, and requires that the facility institute a quality assurance program. Guidelines from the Centers for Disease Control and Prevention (CDC) recommend participation in a proficiency testing program.²²

Preliminary positive rapid tests need to be confirmed with a Western blot or immunofluorescent antibody (IFA) test. For cases such as women in labor, occupational, and non-occupational exposures prophylaxis with antiretroviral agents should be started while the confirmatory test results are pending.^17,19,21