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-1NL4-3 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, immunoblot-negative 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.
Highlights
Effective and timely surveillance of the HIV epidemic is critical for the prevention of virus transmission and a prerequisite for achieving high rates of early antiretroviral treatment
For staging of acute HIV-1 infections based on Fiebig criteria, we evaluated the presence of HIV-1 RNA (PCR) and p24 capsid (p24CA) antigen (p24CA-EIA), as well as the results of the 4G-EIA and immunoblotting: Fiebig stage I (RNA-positive, p24CAEIA-negative, 4G-EIA-negative, immunoblot-negative), Fiebig stages II–III (RNA-positive, p24CA-EIA-positive, 4G-EIA-positive or negative, immunoblot-negative), Fiebig stage IV (RNA-positive, p24CA-EIA-positive or negative, 4G-EIA-positive, immunoblot-indeterminate), Fiebig stage V (RNA-positive, p24CA-EIA-negative or positive, 4G-EIA-positive, immunoblot-positive without p31 band), Fiebig stage VI (RNA-positive, p24CA-EIA-negative or positive, 4G-EIA-positive, immunoblot-positive with p31 band) [16, 38]
We investigated the capabilities of the new rapid diagnostic tests (RDTs) to detect chronic HIV-2 infection as well as p27CA from several HIV-2 strains and primary isolates
Summary
Effective and timely surveillance of the HIV epidemic is critical for the prevention of virus transmission and a prerequisite for achieving high rates of early antiretroviral treatment. Patients suffering from acute HIV infection are difficult to diagnose [3]. These individuals typically suffer from rather non-specific symptoms, yet have viral loads that are about 20 times higher than in the untreated chronic phase of infection, which correlates with a high risk of subsequent transmissions [4, 5]. There is a demand for diagnostic tests that are applicable for monitoring large groups of individuals and that are capable of rapidly identifying acute HIV infections with high sensitivity and specificity
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