Background: There are two FDA-approved 4th generation assays available that have the capability to detect both HIV-1/2 specific antibodies and HIV-1 p24 antigen, allowing for the diagnosis of acute HIV-1 infection (AHI). Both assay are considered reactive at sample/cutoff ratio (S/CO)≥1 and non-reactive at S/CO<1. Since the S/CO signal increases with the quantity of antigen and antibodies presents in the sample, it should be possible to use the S/CO range to differentiate between negative, AHI, recent and established HIV infection status.
Methods: All the samples were run with the Abbott ARCHITECT HIV Ag/Ab Combo CMIA (ARCHITECT) and the Bio-Rad GS HIV Combo Ag/Ab EIA (GSCOMBO). The following testing algorithm was used: S/CO<1 with negative nucleic acid amplification test (NAT): negative; S/CO≥1 with Bio-Rad Multispot HIV-1/2 rapid test (MS) non-reactive and positive NAT: AHI; ARCHITECT or GSCOMBO reactive, MS-reactive with a confirming Western blot (WB) without or with the band p31+ present: recent or established infection, respectively.
Results: A total of 150 clinical specimens were evaluated. Ninety-nine samples with a S/CO<1 were confirmed as negative with an ARCHITECT and GSCOMBO S/CO median and interquartile range [IQR] of 0.11 [0.09-0.13] and 0.27 [0.25-0.28], respectively. Fifty-one samples had a S/CO≥1, of which 25 confirmed as AHI (Fiebig II) with ARCHITECT and GSCOMBO S/CO median [IQR] of 12.5 [4.7-74] and 11.7 [5.8-14], respectively, and with a viral load median [IQR] of 1.07×10^6 RNA copies/mL [6.90×10^5 – 10×10^6]. Of the 26 specimens that were MS reactive and WB positive, 21 specimens were confirmed as established infection (Fiebig VI) and only 5 lacked the WB-p31+ band, which indicated recent infection (Fiebig V). The ARCHITECT S/CO medians [IQR] for recent and established infection were 418 [384-449] and 914 [785-1061] respectively; both S/CO ratios were the same (14 ) for the GSCOMBO. The GSCOMBO S/CO also reached 14 in 40% of AHI (10 samples). There were statistically significant differences in the ARCHITECT S/CO median [IQR] between AHI, recent and long-term infection (Kruskal–Wallis, p<0.0001) but not for GSCOMBO (Figure 1).
Conclusions: In this small study both the GSCOMBO and ARCHITECT identified AHI equally well but the ARCHITECT S/CO dynamic range was able to further differentiate between AHI, recent and established infection. The use of the ARCHITECT S/CO to identify recency of HIV-1 infection requires confirmation in a larger study.