Highlights from the 2016 HIV diagnostics conference: The new landscape of HIV testing in laboratories, public health programs and clinical practice
Introduction
The 2016 HIV Diagnostics Conference, which occurred March 21–24, 2016, in Atlanta, Georgia, was convened by the Centers for Disease Control and Prevention (CDC), the Association of Public Health Laboratories (APHL), the American Sexual Health Association and the American Sexually Transmitted Diseases Association. It was attended by public health officials, laboratorians, HIV testing program managers, surveillance coordinators and industry representatives. This unique confluence of subject matter experts involved in every aspect of HIV testing fosters the development and use of new HIV testing technology in the United States. The conference offers a unique opportunity for persons involved in HIV testing to become familiar with test performance data, the implementation of new testing algorithms, quality assurance, and the application of new tests in a variety of settings. Testing is the gateway to treatment, so, fittingly, attendees emphasized the need to use accurate diagnostic tests and to decrease time to treatment for infected persons to improve health outcomes and prevent infections [1]. This report describes highlights of the conference from the perspectives of co-authors who participated.
Opening night presentations addressed diagnostic terminology and performance measures. There is movement toward describing the analytes an assay detects and away from using “generation” terms (e.g., antigen/antibody immunoassay instead of fourth-generation assay) [2]. There was a discussion on how to evaluate HIV test performance that included the impact on specificity of maximizing sensitivity [3]. If the penalty for missing a case is high (i.e., the disease is fatal, treatment exists or it spreads easily), a test cut-off should be set to maximize true positives, which may increase the number of false positives. When prevalence is low, positive screening test results are often false positive (i.e., low positive predictive value). Further, methods to calculate algorithm performance were discussed. Food and Drug Administration (FDA) staff provided an overview of HIV test regulations and the components of a package insert [4].
Section snippets
HIV laboratory testing algorithm
The 2014 laboratory testing algorithm recommended by CDC and APHL was designed to improve the detection of acute HIV-1 infections, reduce the time to testing completion, and accurately diagnose HIV-2 [5]. An APHL survey indicates that 55% of public health laboratories used the algorithm in 2014 [6]. The algorithm performed as expected. Early infection detection is similar for different laboratory-based antigen/antibody tests, and is better than for IgM-sensitive tests [7]. The likelihood of
Nucleic acid testing
The laboratory testing algorithm provides timely results for antibody positive specimens, particularly when supplemental testing is conducted in the same laboratory [10]. However, delays may occur when nucleic acid testing is needed. Many laboratories do not perform NATs because they are expensive, technically challenging, or needed too infrequently. To compound the issue, only one NAT, a qualitative HIV-1 RNA assay, is approved for diagnostic use in the United States. If a laboratory uses a
Impact of three new tests on the laboratory algorithm
Two screening tests (Determine, and BioPlex 2200 HIV Ag-Ab assay (Bio-Rad Laboratories, Hercules, CA, BioPlex)) and one supplemental antibody test (Geenius HIV-1/2 Supplemental Assay, Bio-Rad Laboratories, Redmond, WA, Geenius) which were recently FDA approved may impact the laboratory algorithm [13]. The Determine rapid test provides separate results for HIV-1 p24 antigen and HIV-1/2 antibody. It detects infection earlier than IgM/IgG sensitive assays when used with plasma, but after
Alternatives to the recommended laboratory algorithm
Two studies examined the signal to cut-off ratio for the ARCHITECT HIV Ag/Ab Combo (Abbott Laboratories, Abbott Park, IL, ARCHITECT). The first provided data on repeating the ARCHITECT in duplicate only when the initial run had a signal to cut-off ratio of less than 10 rather than on all initially reactive samples in order to improve turnaround time and decrease cost [20]. This approach is not FDA-approved, so validation is required. The second indicated that a high signal to cut-off ratio
Surveillance
HIV testing data are used by surveillance units to describe disease burden, monitor progress toward prevention goals, and identify HIV-diagnosed individuals who are not in care so that they can be linked with a provider [22], [23]. Challenges to obtaining accurate, complete data include incomplete reporting of all tests performed for an individual, health care provider confusion with ordering tests and health department/provider confusion with laboratory report interpretation. The surveillance
CLIA-waived testing
A conference session was dedicated to testing that occurs outside of traditional laboratory settings with CLIA-waived rapid tests. CDC staff presented 2016 non-clinical testing guidance which features practical considerations for HIV testing providers and gives information on programmatic issues and updates that impact HIV testing service delivery. It complements “Planning and Implementing HIV Testing and Linkage Programs in Non-clinical Settings”, which includes the benefits and drawbacks for
Linkage to care
In addition to test performance, there were presentations on the real-world application of testing and its impact on linkage to HIV care. When using the laboratory algorithm, some persons may not get their results or results may be delayed. Part of the impetus for beginning a statewide rapid testing algorithm program in New Jersey was the fact that 25% of persons did not receive their Western blot test results after a reactive rapid test [30]. After expanding the program, most people screened
Special testing circumstances
During a session on special testing circumstances, Indiana State Department of Health staff described the evolution of testing strategies to improve sensitivity during an HIV and hepatitis C virus (HCV) outbreak in their state associated with injection drug use [32]. A separate presentation addressed the use of HIV-1 sequence data to infer transmission networks and inform public health action [33].
Staff from the US Military HIV Research Program presented on the impact of early treatment on
New tests for diagnosis, clinical staging, and surveillance
Based on the NASTAD survey, opportunities for testing for multiple pathogens are being missed: only 17% of respondents conducted HCV testing in all settings where HIV testing was provided. To test for HIV and syphilis in a hospital emergency department, separate rapid tests for each pathogen were employed at the point of care by dedicated non-emergency department staff [37]. Rapid tests are in development that detect multiple analytes. Chembio Diagnostics’ DPP HIV-Syphilis Multiplex Rapid Test
Conclusion
The conference highlighted novel HIV testing technology, but accurate tests alone are not sufficient for improving health. Testing processes must be streamlined so that time to treatment is reduced. With respect to the recommended HIV laboratory testing algorithm, alternative tests for the second and third steps are needed that will allow laboratories to conduct all testing in the same facility. Novel technologies such as simplified nucleic acid tests can identify acute infections rapidly and
Conflict of interest
None declared.
Funding
None.
Ethical approval
Not required.
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
Conference management: Lynn Barclay and Fred Wyand.
Scientific Steering Committee (generated call for abstracts, reviewed abstracts and presentations and created conference’s scientific program): Cornelis (Kees) Rietmeijer, MD, PhD, Kelly Wroblewski, MPH, MT (ASCP), Berry Bennett, MPH, Barbara A Body, PhD, D(ABMM), Pollyanna R Chavez, PhD, Steven F Ethridge, MT (ASCP), Indira Hewlett, PhD, Richard L Hodinka, PhD, Eugene Martin, PhD, Joanne Mei, PhD, Chris Pilcher, MD, Liisa Randall, PhD,
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New technology and its impact on the CDC/APHL laboratory testing algorithm
HIV Diagnostics Conference
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HIV Diagnostics Conference
Performance evaluation of HIV supplemental assays
HIV Diagnostics Conference
Comparative performance of the Geenius HIV-1/HIV-2 Supplemental Test in florida’s public health testing population
HIV Diagnostics Conference
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HIV Diagnostics Conference
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HIV Diagnostics Conference
Is it always necessary for the ARCHITECT 4th-Generation HIV-1/2 Ag/Ab Combo assay to be repeatedly reactive before moving forward in the centers for disease control and prevention HIV screening algorithm?
HIV Diagnostics Conference
Performance of the Abbott Architect HIV Ag/Ab Combo assay in the US army HIV diagnostic algorithm
HIV Diagnostics Conference
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HIV Diagnostics Conference
Cited by (7)
BioRad BioPlex® HIV Ag-Ab assay: Incidence of false positivity in a low-prevalence population and its effects on the current HIV testing algorithm
2019, Journal of Clinical VirologyCitation Excerpt :The HIV 1/2 antigen/antibody immunoassays have been shown to produce false positive results, especially in populations with low HIV prevalence [5,6]. False positives are identified as specimens with low reactivity by initial HIV1/2 antigen/antibody immunoassays, which are unable to be confirmed by subsequent testing using varied methodologies, such as the Bio-Rad Geenius™ HIV-1/2 Supplemental Assay and PCR [4,7–10]. BioRad’s BioPlex® HIV Ag-Ab combination assay is a multiplex flow immunoassay that can simultaneously detect and differentiate HIV-1 p24 antigen, HIV-1 (groups M and O) antibodies, and HIV-2 antibodies in human serum or plasma.
Trends in testing algorithms used to diagnose HIV infection, 2011–2015, United States and 6 dependent areas
2018, Journal of Clinical VirologyCitation Excerpt :As a result, a second level of testing was added to improve specificity, and by 1989 the most commonly used HIV diagnostic testing algorithm consisted of an HIV antibody immunoassay (IA) as the initial test, followed by a Western blot (WB) or immunofluorescence assay (IFA) as the supplemental antibody test to confirm reactive results from the initial test [11]. In 2014 the Centers for Disease Control and Prevention (CDC) and the Association of Public Health Laboratories (APHL) issued updated laboratory testing recommendations for the diagnosis of HIV infection to improve the recognition of acute HIV-1 infections and to reduce the time to make a definitive determination of a patient's HIV status [12–16]. The 2014 algorithm consists of an HIV-1 IA that can detect both HIV antigen and antibody, followed by a supplemental IA that can detect HIV antibodies and differentiates between HIV-1 and HIV-2 antibodies.
Performance of an Alternative Laboratory-Based HIV Diagnostic Testing Algorithm Using HIV-1 RNA Viral Load
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2017, Sexually Transmitted Diseases