Comparative multi-assay evaluation of Determine™ HIV-1/2 Ag/Ab Combo rapid diagnostic tests in acute and chronic HIV infection

Abstract

In resource-limited or point-of-care settings, rapid diagnostic tests (RDTs), that aim to simultaneously detect HIV antibodies and p24 capsid (p24CA) antigen with high sensitivity, can pose important alternatives to screen for early infections. We evaluated the performance of the antibody and antigen components of the old and novel version of the Determine™ HIV-1/2 Ag/Ab Combo RDTs in parallel to quantifications in a fourth-generation antigen/antibody immunoassay (4G-EIA), p24CA antigen immunoassay (p24CA-EIA), immunoblots, and nucleic acid quantification. We included plasma samples of acute, treatment-naïve HIV-1 infections (Fiebig stages I-VI, subtypes A1, B, C, F, CRF02_AG, CRF02_AE, URF) or chronic HIV-1 and HIV-2 infections. The tests' antigen component was evaluated also for a panel of subtype B HIV-1 transmitted/ founder (T/F) viruses, HIV-2 strains and HIV-2 primary isolates. Furthermore, we assessed the analytical sensitivity of the RDTs to detect p24CA using a highly purified HIV-1 NL4-3 p24CA standard. We found that 77% of plasma samples from acutely infected, immunoblot-negative HIV-1 patients in Fiebig stages II-III were identified by the new RDT, while only 25% scored positive in the old RDT. Both RDTs reacted to all samples from chronically HIV-1-infected and acutely HIV-1-infected patients with positive immunoblots. All specimens from chronically infected HIV-2 patients scored positive in the new RDT. Of note, the sensitivity of the RDTs to detect recombinant p24CA from a subtype B virus ranged between 50 and 200 pg/mL, mirrored also by the detection of HIV-1 T/F viruses only at antigen concentrations tenfold higher than suggested by the manufacturer. The RTD failed to recognize any of the HIV-2 viruses tested. Our results indicate that the new version of the Determine™ HIV-1/2 Ag/Ab Combo displays an increased sensitivity to detect HIV-1 p24CA-positive, immunoblotnegative plasma samples compared to the precursor version. The sensitivity of 4G-EIA and p24CA-EIA to detect the major structural HIV antigen, and thus to diagnose acute infections prior to seroconversion, is still superior.

A Comparative Analysis of the different HIV Testing Techniques used in Zambia: Data from a Clinical Performance Study

“…19 In resource-limited or point-of-care settings, rapid diagnostic tests (RDTs), that aim to simultaneously detect HIV antibodies and p24 capsid (p24CA) antigen with high sensitivity, can pose important alternatives to screen for early infections. 20 Given the brief window of acute HIV infection, the acute HIV prevalence in a population is very low at any given point in time, even among relatively high-risk groups. Consequently, a test must have exceptional performance characteristics to be useful, especially without additional con rmatory testing.…”

Diagnostic performance evaluation of urine HIV-1 antibody rapid test kits in a real-life routine care setting in China

“…Considering the complexities and psychologically protective behaviours of some subjects undergoing VCT, it may be more appropriate to choose an antigen-antibody combined reagent with higher sensitivity and specificity to reduce the possibility of false negatives in some cases where it is difficult for physicians treating these subjects to obtain true and accurate information 30 31. Some subjects with significant psychological fear of HIV but no high-risk exposure may consider using non-invasive urine reagent strips to reduce trauma and receive psychological counselling.…”

Comparing the Performance of HIV Rapid Diagnostic Tests used in Zambia - A Systematic Clinical Data Review

“…19 In resource-limited or point-of-care settings, rapid diagnostic tests (RDTs), that aim to simultaneously detect HIV antibodies and p24 capsid (p24CA) antigen with high sensitivity, can pose important alternatives to screen for early infections. 20 Given the brief window of acute HIV infection, the acute HIV prevalence in a population is very low at any given point in time, even among relatively high-risk groups. Consequently, a test must have exceptional performance characteristics to be useful, especially without additional confirmatory testing.…”