False-Positive Rate of a “Fourth-Generation” HIV Antigen/Antibody Combination Assay in an Area of Low HIV Prevalence

Abstract

We retrospectively analyzed the performance of the Architect HIV antigen/antibody (Ag/Ab) combination assay in a tertiary health care center with a situation of low HIV prevalence. The specificity and positive predictive value (PPV) were 99.78% and 31.21%, respectively. However, the specificity and PPV could increase to 99.99% and 89.70% using an arbitrary cutoff value.Since the first HIV test was introduced in 1985, the performances of HIV screening assays have improved continuously. In particular, the HIV antigen/antibody (Ag/Ab) combination assays launched in 1997 have shortened the window period by 4 to 5 days compared to those of the previous antibody-alone enzyme immunoassays (8). After the improvement of the detection limit of the p24 antigen enzyme immunoassay (EIA) to equivalent to that of the single-antigen EIA, HIV Ag/Ab combination assays have been implemented in numerous laboratories throughout the world (7, 9).The Centers for Disease Control and Prevention (CDC) recommended the expansion of HIV antibody testing from targeted, risk-based testing to universal screening of all adults aged 13 to 64 years in health care settings (2). Although the revised recommendation could be effective in identifying the maximum possible number of HIV-infected people from a public health perspective, there are concerns about false-positive results (3, 11). False-positive HIV screening results could cause substantial psychological distress while waiting for a confirmatory test (10). Guinn estimated the positive predictive value (PPV) of rapid HIV testing in Oregon with 100% sensitivity and 99.9% specificity to be 29% (3). The rate of falsepositive results could be dramatically increased in situations of extremely low HIV prevalence. Shima-Sano et al. reported that the PPV of HIV screening results in pregnant women is only 3.7% (5).According to a report by the Korea Centers for Disease Control and Prevention, 6,120 individuals have been diagnosed with an HIV infection between 1985 and 2008 in Korea (4). Although the number of newly diagnosed HIV infections has increased, the cumulative number of HIV-infected individuals and prevalence were lower than those in other countries. There has been limited study on the rate of false-positive results in HIV screening tests using an automated HIV Ag/Ab combination assay. In the present study, we retrospectively analyzed the performance of an automated HIV Ag/Ab combination assay in a tertiary health care center with a situation of low HIV prevalence.

Human Immunodeficiency Virus Diagnostic Testing: 30 Years of Evolution

“…Similar results for the Architect procedure were recently reported by Muthukumar et al (14). Positive predictive values may be increased further by determining a different cutoff value appropriate for the population to be tested (15).…”

Performance of the Liaison XL Murex HIV Ab/Ag Test on Clinical Samples Representing Current Epidemic HIV Variants

“…We also found true-positive samples with similar low values, which corresponded mostly to early stages of the infection, but also to group O HIV variants. These observations highlight the need for caution during the interpretation of indexes around the cutoff and the need for complementary analysis to avoid misinterpretation (18).…”

A Signal-to-Cutoff Ratio in the Abbott Architect HIV Ag/Ab Combo Assay That Predicts Subsequent Confirmation of HIV-1 Infection in a Low-Prevalence Setting

“…Other studies with small samples have suggested a relationship between the S/CO ratio in HIV Ag/Ab assays and confirmed HIV infection or the HIV viral load (VL) (1,(6)(7)(8). As the somewhat time-consuming HIV WB test is the currently approved confirmatory test in Australia, we assessed the positive predictive value of the Abbott Combo assay in this low-prevalence population.…”