Failure of A Novel, Rapid Antigen and Antibody Combination Test to Detect Antigen-Positive HIV Infection in African Adults with Early HIV Infection

Abstract

BackgroundAcute HIV infection (prior to antibody seroconversion) represents a high-risk window for HIV transmission. Development of a test to detect acute infection at the point-of-care is urgent.MethodsVolunteers enrolled in a prospective study of HIV incidence in four African cities, Kigali in Rwanda and Ndola, Kitwe and Lusaka in Zambia, were tested regularly for HIV by rapid antibody test and p24 antigen ELISA. Five subgroups of samples were also tested by the Determine Ag/Ab Combo test 1) Antigen positive, antibody negative (acute infection); 2) Antigen positive, antibody positive; 3) Antigen negative, antibody positive; 4) Antigen negative, antibody negative; and 5) Antigen false positive, antibody negative (HIV uninfected). A sixth group included serial dilutions from a p24 antigen-positive control sample. Combo test results were reported as antigen positive, antibody positive, or both.ResultsOf 34 group 1 samples with VL between 5x105 and >1.5x107 copies/mL (median 3.5x106), 1 (2.9%) was detected by the Combo antigen component, 7 (20.6%) others were positive by the Combo antibody component. No group 2 samples were antigen positive by the Combo test (0/18). Sensitivity of the Combo antigen test was therefore 1.9% (1/52, 95% CI 0.0, 9.9). One false positive Combo antibody result (1/30, 3.3%) was observed in group 4. No false-positive Combo antigen results were observed. The Combo antigen test was positive in group 6 at concentrations of 80 pg/mL, faintly positive at 40 and 20 pg/mL, and negative thereafter. The p24 ELISA antigen test remained positive at 5 pg/mL.ConclusionsAlthough the antibody component of the Combo test detected antibodies to HIV earlier than the comparison antibody tests used, less than 2% of the cases of antigen-positive HIV infection were detected by the Combo antigen component. The development of a rapid point-of-care test to diagnose acute HIV infection remains an urgent goal.

Multi-Centre Evaluation of the Determine HIV Combo Assay when Used for Point of Care Testing in a High Risk Clinic-Based Population

“…The DHC package insert reports 25 pg/ml as the lower limit of p24 antigen detection and independent studies confirmed the lower limit to be 20–50 pg/ml when using serial dilutions of p24 antigen serum control [37], [42]. However, the p24 antigen lower limit of detection for clinical specimens appears higher: in one study 51 antigen positive plasma specimens ranging 8–457 (median 94) pg/ml remained undetected [42]; and in our study nine fingerstick blood specimens ranging 66–701 (median 115) pg/ml remained undetected. Hence, the DHC antigen lower limit of detection when used with clinical specimens, as opposed to serum control specimens, requires further investigation and clarification.…”

The performance of the Alere HIV combo point-of-care test on stored serum samples; useful for detection of early HIV-1 infections?

“…Reported sensitivities varied from 0% (0/2 samples;3 0/8,4), 0% (0/13,5), 3% (1/34,6), 23% (13/57,7), 50% (3/6,8), 54% (14/269) to 67% (26/3910). …”

Poor Performance of the Determine HIV-1/2 Ag/Ab Combo Fourth-Generation Rapid Test for Detection of Acute Infections in a National Household Survey in Swaziland

“…The Determine HIV-1/2 Ag/Ab combo rapid test is the first such test that detects both Ag and Ab in two separate indicator lines. Early data on the performance of the Determine combo test to detect acute HIV infections in seroconversion panels suggested that it had a good performance in detecting early infections (19,20 (21)(22)(23)(24)(25)(26)(27)(28). Several of the studies were limited by small sample size and failure to follow up potential acute infections for seroconversion.…”