Elsevier

Journal of Clinical Virology

Volume 91, June 2017, Pages 95-100
Journal of Clinical Virology

Performance evaluation of the FDA-approved Determine™ HIV-1/2 Ag/Ab Combo assay using plasma and whole blood specimens

https://doi.org/10.1016/j.jcv.2017.03.019Get rights and content

Highlights

  • Determine Combo performs significantly better with plasma than with whole blood.

  • Determine Combo missed a high proportion of acute HIV-1 infections using plasma.

  • Determine Combo is less sensitive than an instrumented laboratory-based Ag/Ab assay.

Abstract

Background

The Determine™ HIV-1/2 Ag/Ab Combo (DC) rapid test can identify HIV-1 infection earlier than rapid antibody-only tests in plasma specimens.

Objectives

We compared the performance of DC with a laboratory-based antigen/antibody (Ag/Ab) combo assay in plasma and evaluated antigen reactivity in whole blood specimens.

Study design

We tested by DC 508 plasma specimens collected in a prospective study and 107 sequential plasma and simulated whole blood specimens from 20 seroconversion panels. Previous results using the ARCHITECT (ARC) Ag/Ab combo assay were compared to DC results. In seroconversion panels, the days from the first HIV1 RNA-positive test to first DC-reactive in plasma and whole blood was compared. McNemar’s and Wilcoxon signed rank tests were used for statistical analysis.

Results

Of 415 HIV-positive samples, ARC detected 396 (95.4%) and DC 337 (81.2%) (p < 0.0001). DC was reactive in 50.0% of ARC-reactive/MS-negative, 78.6% of ARC-reactive/MS-indeterminate, and 99.6% of ARC-reactive/MS-HIV-1-positive or −undifferentiated specimens. DC antigen reactivity was higher among ARC-reactive/MS-negative than MS-indeterminate samples. In 20 HIV-1 seroconversion panels, there was a significant difference between DC reactivity in plasma (91.1%) and whole blood (56.4%) (p < 0.0001). DC with whole blood showed a significant delay in reactivity compared to plasma (p = 0.008).

Conclusions

In plasma, DC was significantly less sensitive than an instrumented laboratory-based Ag/Ab combo assay. DC in plasma was significantly more sensitive compared to whole blood in early HIV-1 infections. With the U.S. laboratory-based diagnostic algorithm, DC as the first step would likely miss a high proportion of HIV-1 infections in early stages of seroconversion.

Section snippets

Background

In 2014 the Centers for Disease Control and Prevention (CDC) and the American Public Health Laboratories (APHL) published an updated HIV diagnostic algorithm for laboratory settings. The updated algorithm recommends screening with an HIV antigen/antibody (Ag/Ab) combination assay followed by a supplemental assay that differentiates between HIV-1 and HIV-2 antibodies. An HIV-1 RNA test is used to resolve discrepant results. With Food and Drug Administration (FDA) approval of new HIV diagnostic

Objectives

We evaluated the performance of DC with plasma specimens from persons enrolled in a study to identify acute infections as the first step of the CDC/APHL HIV laboratory diagnostic algorithm. Additionally, we evaluated both antigen reactivity in simulated whole blood made from commercial seroconversion panels and overall test performance in plasma and simulated whole blood early after infection.

Plasma specimens from the STOP study

The Screening Targeted Populations to Interrupt On-going Chains of HIV Transmission with Enhanced Partner Notification (STOP) study was a prospective study to evaluate methods to detect acute HIV infection (AHI) among high-risk populations in New York City, North Carolina and San Francisco. The study provided an unique opportunity to evaluate improved detection of early HIV infections with the CDC/APHL HIV laboratory diagnostic testing algorithm using the instrumented Abbott ARCHITECT HIV Ag/Ab

DC performance on plasma specimens from the STOP study

Of 508 STOP study plasma specimens available, 142 were from NYC, 37 from NC and 329 from SF. 277 SF specimens were unique and 52 had two or three follow-up plasma specimens that initially were RT-antibody negative. Table 1 shows the distribution of plasma specimens classified by previous testing at different sites.

None of the 508 plasma specimens tested invalid with DC. Of 415 HIV-positive samples, ARC detected 396 (95.4%) and DC 337 (81.2%) (Table 2). All 19 plasma specimens from AHIs that

Discussion

This evaluation describes the comparison of DC with plasma specimens collected during a multi-site study in high-risk populations to a laboratory-based Ag/Ab combo assay used as a first step in the CDC/APHL HIV diagnostic algorithm for laboratory settings used in the U.S. [2]. We also describe the performance of DC in plasma and simulated whole blood during early stages of HIV-1 infection.

For the study, sequential plasma specimens were analyzed independently to assess DC reactivity in the

Competing interest

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

Fundings

This research was supported by a cooperative agreement between the Centers for Disease Control and Prevention (CDC) and the San Francisco Department of Public Health (5U01PS001564), New York City Department of Health and Mental Hygiene (5U01PS001561), and the University of North Carolina at Chapel Hill (5U01PS001559) and CDC intramural funding.

Ethical approval

The STOP study was approved by the Institutional Review Boards for the University of California at San Francisco, the University of North Carolina at Chapel Hill, and the New York City Department of Health & Mental Hygiene (HSR 6193).

Disclaimer

The findings and conclusions in this study are those of the authors and do not necessarily represent the views of the U.S. Department of Health and Human Services, or the U.S. Centers for Disease Control and Prevention. Use of trade names and commercial sources is for identification only and does not constitute endorsement by the U.S. Department of Health and Human Services, or the U.S. Centers for Disease Control and Prevention.

Acknowledgments

We are thankful for contributions of the STOP teams and study participants in New York City, North Carolina and San Francisco. We also acknowledge William M. Switzer, for kindly reviewing this manuscript.

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