Performance of the Alere Determine™ HIV-1/2 Ag/Ab Combo Rapid Test with specimens from HIV-1 seroconverters from the US and HIV-2 infected individuals from Ivory Coast

doi:10.1016/j.jcv.2013.07.002

Journal of Clinical Virology

Volume 58, Supplement 1, December 2013, Pages e54-e58

https://doi.org/10.1016/j.jcv.2013.07.002 Get rights and content

Abstract

Background

FDA-approved HIV Antigen/Antibody combo (4th generation) immunoassays (IAs) can identify HIV-1 infections before the Western blot (WB) becomes positive. In the US, increased detection of acute HIV infections has been facilitated by using 4th generation IAs, but there is no FDA-approved 4th generation rapid test (RT). The Alere Determine™ HIV-1/2 Ag/Ab Combo (Determine Combo) RT detects and distinguishes HIV p24 Antigen (Ag) from Antibody (Ab) to HIV-1 + HIV-2 and thus has the potential to improve diagnosis of acute HIV infection.

Objective

To evaluate the ability of Determine Combo RT to detect acute/early HIV-1 infections and HIV-2 antibody in well-characterized plasma specimens.

Study design

In HIV-1 seroconverters from the US, Determine Combo reactivity was evaluated by performing the 50% cumulative frequency analysis and by comparing with 3rd and 4th generation IAs’ reactivity. HIV-2 plasma specimens from Ivory Coast were tested with Determine Combo.

Results

The 50% cumulative frequency analysis in 17 seroconverters placed Determine Combo (Ag+/Ab−, Ag+Ab+, Ag−/Ab+) and Ab-component reactivity at 15.5 and 7 days before WB positivity, respectively. In 26 seroconverters, Determine Combo was reactive in 99.0% and 92.5% of 3rd and 4th generation IAs-reactive specimens, respectively. All HIV-2 plasma specimens were Ab-reactive/Ag-non-reactive by Determine Combo.

Conclusions

Based on previous results with the same seroconversion panels, combined Ag/Ab reactivity of the Determine Combo appears between FDA-approved 4th and 3rd generation laboratory IAs. These data indicate that this RT could detect HIV-1 infection earlier than other RTs and it performs well in HIV-2 specimens.

Section snippets

Background

Simultaneous detection of HIV antigen (Ag) and antibodies (Ab) by 4th generation combo immunoassays (IAs) narrows the HIV diagnostic window period, improving identification of acute/early infections while maintaining accurate detection of established infections. [1], [2], [3], [4] Previous data from a relative sensitivity analysis of specimens from HIV seroconverters indicate the laboratory-based 4th generation IAs available in the United States (US) detect HIV-1 infection approximately 18–20

Objectives

This study used well characterized plasma specimens from HIV-1 seroconverters that have been previously used to evaluate FDA-approved assays [4] and specimens from HIV-2 groups A and B infected individuals from Ivory Coast to evaluate the ability of the modified Determine Combo to detect acute/early HIV-1 infections and HIV-2 antibodies.

HIV assays

The Alere Determine™ HIV-1/2 Ag/Ab Combo, manufactured by Orgenics, Ltd. (Yavne, Israel), was kindly provided by Alere Medical Co., Ltd. The assay was performed as indicated in the package insert [6] for frozen plasma specimens. All specimens were tested in singlet and repeated only if invalid results were obtained as previously reported. [4], [17]

The Genetic Systems™ HIV-1/2 plus O (GS + O) and HIV-1/2 Combo Ag/Ab IAs (GS Combo) (Bio-Rad Laboratories, Redmond, WA) were used as comparator assays

Cumulative frequency analysis

The relative sensitivity of the overall Determine Combo assay and the Determine Ab-only component in plasma specimens was estimated by calculating the 50% cumulative frequency as described above and compared to previous estimates for FDA-approved assays from the same specimen set. [4] The sequence of test reactivity expressed as the number of days before the first positive WB is shown in Fig. 1. The Determine Combo reactivity was estimated to be 15.5 days before the first positive WB and places

Discussion

Our study is the first to report on the performance of the 2011 version of Alere Determine™ HIV-1/2 Ag/Ab combo RT in plasma specimens collected during early stages of HIV-1 infection. The results from the relative sensitivity analysis (compared with previously published results from 14 FDA-approved HIV tests performed on the same seroconversion panels) [4], [18] indicates that the Determine Combo RT is reactive approximately 15.5 days before a positive WB, between the time of reactivity of 4th

Funding

Centers for Disease Control intramural fundings.

Competing interest

No financial disclosures were reported by the authors of this paper.

Ethical approval

No ethical approval was sought because all specimens used in this study were from commercially available sources and contained no personal identifiers.

Disclaimer

The findings and conclusions in this report are ours and do not necessarily represent the views of the Centers for Disease Control and Prevention. Use of brand names is for identification purposes and does not imply endorsements by the US Department of Health and Human Services.

Acknowledgements

The authors would like to thank Alere Medical Co., Ltd for providing the Determine™ HIV-1/2 Ag/Ab Combo test for this study and to Bernard Branson for his critical review of the manuscript.

References (22)

P. Chavez et al.
Evaluation of the performance of the Abbott ARCHITECT HIV Ag/Ab Combo Assay
Journal of Clinical Virology
(2011)
C. Bentsen et al.
Performance evaluation of the Bio-Rad Laboratories GS HIV Combo Ag/Ab EIA, a 4th generation HIV assay for the simultaneous detection of HIV p24 antigen and antibodies to HIV-1 (group M and O) and HIV-2 in human serum or plasma
Journal of Clinical Virology
(2011)
T. Pumarola et al.
Performance evaluation of the ADVIA Centaur^® HIV Ag/Ab Combo Assay
Journal of Virological Methods
(2010)
S. Masciotra et al.
Evaluation of an alternative HIV diagnostic algorithm using specimens from seroconversion panels and persons with established HIV infections
Journal of Clinical Virology
(2011)
P. Patel et al.
Rapid HIV screening: missed opportunities for HIV diagnosis and prevention
Journal of Clinical Virology
(2012)
E.G. Martin et al.
Use of a rapid testing algorithm to improve linkage to care
Journal of Virological Methods
(2011)
G. Beelaert et al.
Evaluation of a rapid and simple fourth-generation HIV screening assay for qualitative detection of HIV p24 antigen and/or antibodies to HIV-1 and HIV-2
Journal of Virological Methods
(2010)
V. Chetty et al.
Evaluation of a 4th generation rapid HIV test for earlier and reliable detection of HIV infection in pregnancy
Journal of Clinical Virology
(2012)
M.P. Busch et al.
Time course of viremia and antibody seroconversion following human immunodeficiency virus exposure
The American Journal of Medicine
(1997)
T.D. Ly et al.
The variable sensitivity of HIV Ag/Ab combination assays in the detection of p24Ag according to genotype could compromise the diagnosis of early HIV infection
Journal of Clinical Virology
(2012)

Alere Medical Co., Ltd.

Determine™ HIV-1/2 Ag/Ab Combo package insert

(2011)

Cited by (57)

Performance evaluation of the MedMira reveal G4 LAB S/P and POC HIV antibody rapid screening tests using plasma and whole blood specimens
2020, Journal of Clinical Virology
The Reveal G4 antibody rapid test is FDA-approved for HIV-1 detection using the versions LAB S/P and POC in CLIA-moderate complexity settings with serum/plasma and whole blood, respectively. The same Reveal tests are CE-marked for HIV-1 and HIV-2 detection in laboratory and point-of-care (POC) settings.
We compared the performance of G4 LAB S/P with plasma and POC with whole blood (blood) for detecting early and established HIV-1/HIV-2 infections.
Matched well-characterized plasma and simulated blood were used to evaluate: sensitivity in 104 HIV-1 and 55 HIV-2 established infections, specificity in 49 HIV-negative, and reactivity in early HIV-1 infection in a performance panel (n=38) and 18 plasma panels from seroconverters (SCs, n=183). Median number of days after first RNA-positive was calculated for 13 SCs. Impact of viral suppression (VS) was evaluated in 3 SCs receiving early antiretroviral therapy (ART).
Sensitivity was 100 % for HIV-1 and 98.18 % for HIV-2, while specificity was 100 %. All 38 plasma and blood become reactive by Fiebig stage V. Of 18 SCs, 10 had similar reactivity in plasma/blood, 7 showed delayed reactivity in blood, and 1 was nonreactive in plasma/blood. The median days for a G4-reactive after first RNApositive was 13 for plasma and 14 for blood. Long-term VS had no impact on G4 reactivity.
Overall reactivity in early HIV-1 infections is delayed by one day in blood compared to plasma. If FDA-approved for POC settings, the G4 POC is a fast sensitive screening tool for HIV-1/HIV-2-specific IgG even during VS.
Performance evaluation of four point-of-care HIV tests using unprocessed specimens
2020, Journal of Clinical Virology
Citation Excerpt :
Since 2012, the U.S. Food and Drug Administration (FDA) has approved several POC tests aiming to identify HIV infections earlier (Table 1). Their performance has been evaluated using plasma, serum, and in some cases simulated whole blood [5–9] or unprocessed oral fluid (OF) or whole blood (WB) [10,11]. However, these newer tests have not all been evaluated in real-world settings, including among persons receiving HIV pre-exposure prophylaxis (PrEP).
The performance of recently approved point-of-care (POC) HIV tests should be assessed using unprocessed specimens.
To evaluate the sensitivity and specificity of four POC HIV tests using whole blood (WB) and two using oral fluid (OF) among persons recruited from health clinics in Seattle, Washington, during September 2015-September 2017.
Participants were tested with the POC tests, additional plasma and serum were collected for laboratory testing, and participant- reported use of antiretroviral therapy (ART) or pre-exposure prophylaxis (PrEP) was recorded. Participants testing negative on all tests could reenroll every 90 days. Specimens from persons previously diagnosed with HIV infection as well as from those who were newly diagnosed during the study were included in the sensitivity estimate. Sensitivity and specificity were calculated based on HIV status determined by laboratory testing.
Of 1,256 visits, 179 were from persons with HIV infection; 120 of these were taking ART. Among 1,077 visits from participants not diagnosed with HIV, PrEP use was reported at 155 (14.4%) visits. Sensitivity was similar among POC WB tests (95.53%-97.21%; p>0.05). Among participants on ART, sensitivity was lower for the same test performed on OF compared to WB (p<0.003). Specificity was high for all tests (99.44%- 100.00%); we did not detect specificity differences with PrEP use.
These POC tests displayed relatively high sensitivity and specificity using unprocessed specimens, suggesting their effectiveness in identifying HIV infections whenever laboratory-based testing is not feasible. Nonetheless, clients with recent risk should retest to rule out the possibility of a false-negative result.
Performance evaluation of the Bio-Rad Geenius HIV 1/2 supplemental assay
2019, Journal of Clinical Virology
Citation Excerpt :
The HIV-2 specimens characterized in the field were further tested at CDC with BRC, Geenius, andHIV-2 WB. Sequence analysis of the integrase region revealed that a third of samples from Ivory Coast were genotypes A, B and A/B recombinants [12]. Serial plasma specimens from 17 HIV-1 seroconverters were used to estimate the relative seroconversion reactivity of Geenius and MS as a supplemental assay.
In the US, the HIV diagnostic algorithm for laboratory settings recommends the use of an HIV-1/HIV-2 differentiation supplemental assay after an initial reactive antigen/antibody (Ag/Ab) assay result. Since the discontinuation of the Multispot HIV-1/HIV-2 Rapid Test (MS), the Geenius HIV-1/2 Supplemental assay (Geenius) is the only FDA-approved supplemental differentiation test.
We compared the performance of Geenius to MS and Western Blot (WB).
The relative seroconversion plasma reactivity of Geenius and MS was assessed using a 50% cumulative frequency analysis from 17 HIV-1 seroconverters. In addition, previously characterized plasma specimens, 186 HIV-1 positive, 100 HIV-2 positive, and 93 Ag/Ab-positive/HIV-1 RNA-negative, were tested with Geenius v1.1 software. McNemar’s test was used for paired comparison analysis. A subset of 48 specimens were retested with the upgraded Geenius v1.3 software.
In HIV-1 seroconverters, the relative seroconversion reactivity was 2.5 and 2 days before the first positive HIV-1 WB for Geenius and MS, respectively. In HIV-1 positive samples, Geenius performed similarly to HIV-1 WB (p=0.1687) and MS (p=0.8312). In HIV-2 positive samples, Geenius underperformed compared to HIV-2 WB (p=0.0005) and MS (p=0.0012). When using the upgraded software among the HIV-1 positive and Ag/Ab-reactive/HIV-1 RNA-negative samples, gp140 reactivity decreased without affecting characterization of HIV-2 samples.
With HIV-1 samples, Geenius, WB and MS performance was similar as supplemental tests. The updated Geenius software reduced false gp140 reactivity, but had no impact on identifying true HIV-2 infections. Further evaluation will assess the impact of the Geenius software update on final diagnostic interpretations
Performance of the Alere Determine™ HIV-1/2 Ag/Ab Combo Rapid Test with algorithm-defined acute HIV-1 infection specimens
2018, Journal of Clinical Virology
The capacity of HIV Antigen/Antibody (Ag/Ab) immunoassays (IA) to detect HIV-1 p24 antigen has resulted in improved detection of HIV-1 infections in comparison to Ab-only screening assays. Since its introduction in the US, studies have shown that the Determine HIV-1/2 Ag/Ab Combo assay (Determine Ag/Ab) detects HIV infection earlier than laboratory-based IgM/IgG-sensitive IAs, but its sensitivity for HIV-1 p24 Ag detection is reduced compared to laboratory-based Ag/Ab assays. However, further evaluation is needed to assess its capacity to detect acute HIV-1 infection.
To assess the performance of Determine Ag/Ab in serum from acute HIV-1 infections.
Select serum specimens that screened reactive on a laboratory-based Ag/Ab IA or IgM/IgG Ab-only IA, with a negative or indeterminate supplemental antibody test and detectable HIV-1 RNA were retrospectively tested with Determine Ag/Ab. Results were compared with those of the primary screening immunoassay to evaluate concordance within this set of algorithm-defined acute infections.
Of 159 algorithm-defined acute HIV-1 specimens, Determine Ag/Ab was reactive for 105 resulting in 66.0% concordance. Of 125 that were initially detected by a laboratory-based Ag/Ab IA, 81 (64.8%) were reactive by Determine Ag/Ab. A total of 34 acute specimens were initially detected by a laboratory-based IgM/IgG Ab-only IA and 24 (70.6%) of those were reactive by Determine Ag/Ab.
Due to their enhanced sensitivity, laboratory-based Ag/Ab IAs continue to be preferred over the Determine Ag/Ab as the screening method used by laboratories conducting HIV diagnostic testing on serum and plasma specimens.
A rapid ultrasound particle agglutination method for HIV antibody detection: Comparison with conventional rapid HIV tests
2017, Journal of Virological Methods
Citation Excerpt :
Since the UPA method is a rapid test, the comparison of its analytical performance with those for other rapid tests irrespective of the detection system they use makes sense. It is worth noting that Multispot and Alere Determine HIV-1/2 antibody tests are among the most widely used and most sensitive conventional rapid HIV antibody tests available on the market (Masciotra et al., 2013). For this reason, the Multispot assay, despite that it is a confirmatory (supplemental) test, among the others, was selected for comparison with the UPA method.
We present the results of the feasibility and preliminary studies on analytical performance of a rapid test for detection of human immunodeficiency virus (HIV) antibodies in human serum or plasma that is an important advance in detecting HIV infection. Current methods for rapid testing of antibodies against HIV are qualitative and exhibit poor sensitivity (limit of detection). In this paper, we describe an ultrasound particle agglutination (UPA) method that leads to a significant increase of the sensitivity of conventional latex agglutination tests for HIV antibody detection in human serum or plasma. The UPA method is based on the use of: 1) a dual mode ultrasound, wherein a first single-frequency mode is used to accelerate the latex agglutination process, and then a second swept-frequency mode of sonication is used to disintegrate non-specifically bound aggregates; and 2) a numerical assessment of results of the agglutination process. The numerical assessment is carried out by optical detection and analysis of moving patterns in the resonator cell during the swept-frequency mode. The single-step UPA method is rapid and more sensitive than the three commercial rapid HIV test kits analyzed in the study: analytical sensitivity of the new UPA method was found to be 510-, 115-, and 80-fold higher than that for Capillus™, Multispot™ and Uni-Gold™ Recombigen HIV antibody rapid test kits, respectively. The newly developed UPA method opens up additional possibilities for detection of a number of clinically significant markers in point-of-care settings.
The fourth generation Alere<sup>TM</sup> HIV Combo rapid test improves detection of acute infection in MTN-003 (VOICE) samples
2017, Journal of Clinical Virology
Citation Excerpt :
These data support the use of CE-HIV Combo in HIV diagnostic algorithms in high incidence settings. Numerous studies have found the antigen component in fourth generation RDT to be insensitive and have reported that these tests do not provide any advantage for the diagnosis of acute infection [4–6,9,10,14–17]. Notably, we found major differences in test performance using two different versions of the same rapid test from the same company; CE-HIV Combo detected 21% more acute infections than FDA-Determine™ Combo.
Early and accurate detection of HIV is crucial when using pre-exposure prophylaxis (PrEP) for HIV prevention to avoid PrEP initiation in acutely infected individuals and to minimize the risk of drug resistance in individuals with breakthrough infection.
To determine if fourth-generation antigen/antibody (Ag/Ab) rapid diagnostic tests (RDT) would have detected HIV infection earlier than the third-generation RDT used in MTN-003 (VOICE).
5029 VOICE participants were evaluated with third-generation Alere Determine™ HIV-1/2, OraQuick ADVANCE^® Rapid HIV-1/2, Uni-Gold™ Recombigen^® HIV-1/2 and Bio-Rad GS HIV-1/2 + O EIA; and fourth-generation Alere Determine™ HIV-1/2 Ag/Ab Combo, Conformité Européene (CE)-Marked Alere™ HIV Combo and Bio-Rad HIV Combo Ag/Ab EIA. Multispot^®, GS HIV-1 Western Blot (WB) and Geenius™ (Bio-Rad) were also evaluated.
Of 57 antibody-negative pre-seroconversion plasma samples with HIV RNA >20 copies/mL identified, 16 (28%) were reactive by CE-Marked Alere™ HIV Combo (1 Ab; 9 Ag; 6 Ag/Ab reactive) and 4 (7%) by Alere Determine™ HIV-1/2 Ag/Ab Combo (2 Ab; 2 Ag; 0 Ag/Ab reactive) (p = 0.0005). Multispot^® confirmed only 1 of 16 acute infections while WB and Geenius™ confirmed none. GS HIV Combo Ag/Ab EIA identified 27 of 57 (47%) pre-seroconversion RNA-positive samples.
In VOICE, 28% of infections missed by current third-generation RDT would have been identified with the use of CE-Marked Alere™ HIV Combo. Geenius™, Multispot^® and WB were all insensitive ( < 10%) in confirming infections detected by fourth-generation assays. An improved diagnostic algorithm that includes a fourth-generation RDT with HIV RNA testing will be essential for efficiently identifying seroconverters on PrEP.

View all citing articles on Scopus

View full text

Published by Elsevier B.V.

Performance of the Alere Determine™ HIV-1/2 Ag/Ab Combo Rapid Test with specimens from HIV-1 seroconverters from the US and HIV-2 infected individuals from Ivory Coast

Abstract

Background

Objective

Study design

Results

Conclusions

Section snippets

Background

Objectives

HIV assays

Cumulative frequency analysis

Discussion

Funding

Competing interest

Ethical approval

Disclaimer

Acknowledgements

Journal of Clinical Virology

Journal of Clinical Virology

Journal of Virological Methods

Journal of Clinical Virology

Journal of Clinical Virology

Journal of Virological Methods

Journal of Virological Methods

Journal of Clinical Virology

The American Journal of Medicine

Journal of Clinical Virology

Determine™ HIV-1/2 Ag/Ab Combo package insert