Access HIV Ag/Ab combo; Access HIV Ag/Ab combo Calibrators; Access HIV Ag/Ab combo QC

BK230833 · Beckman Coulter, Inc. Chaska, MN · MZF · Jul 27, 2023 · Microbiology

Device Facts

• Record ID: BK230833
• Device Name: Access HIV Ag/Ab combo; Access HIV Ag/Ab combo Calibrators; Access HIV Ag/Ab combo QC
• Applicant: Beckman Coulter, Inc. Chaska, MN
• Product Code: MZF · Microbiology
• Decision Date: Jul 27, 2023
• Decision: SESE
• Regulation: 21 CFR 866.3956
• Device Class: Class 2
• Attributes: Real-World Evidence, Pediatric

Real-World Evidence

Submission	Device	Sponsor	RWD Sources	RWE Use Summary	Key Tags
BK230833 · Jul 27, 2023	Access HIV Ag/Ab combo; Access HIV Ag/Ab combo Calibrators; Access HIV Ag/Ab combo QC	Beckman Coulter, Inc. Chaska, MN	Retrospective clinical samples from known positive HIV or high-risk patients	Retrospective samples were used to supplement the clinical performance evaluation (sensitivity and specificity) of the Access HIV Ag/Ab combo assay alongside prospectively collected samples.	Retrospective samples; Clinical sensitivity; Clinical specificity; HIV diagnosis

Clinical Evidence

Study Design	Population	Comparator	Key Endpoints
Clinical Performance Evaluation of Access HIV Ag/Ab combo; Multi-center study using prospectively collected and retrospective pre-characterized samples	Adult, pediatric (ages 2-21), and pregnant subjects; high-risk, low-risk, and known HIV positive; Sample Size: 10,254 total samples (1,175 retrospective); Number of Sites: Multi-center (specific number not provided)	FDA approved HIV Ag/Ab combo comparator assay	Clinical sensitivity and specificity for HIV-1/2 detection

Indications for Use

The Access HIV Ag/Ab combo assay is a paramagnetic particle, chemiluminescent immunoassay for the simultaneous qualitative in vitro detection and differentiation of HIV-1 p24 antigen and antibodies to HIV-1 (groups M and O) and/or HIV-2 in human pediatric (ages 2 through 21 years) and adult serum and serum separator tubes or plasma [lithium heparin, lithium heparin separator tubes, dipotassium (K₂) EDTA, tripotassium (K₃) EDTA, sodium citrate, acid-citrate-dextrose (ACD) and citrate phosphate-dextrose (CPD)] using the DxI 9000 Access Immunoassay Analyzer. The Access HIV Ag/Ab combo assay is intended to be used as an aid in the diagnosis of HIV-1 and/or HIV-2 infection, including acute or primary HIV-1 infection. The assay may also be used as an aid in the diagnosis of HIV-1 and/or HIV-2 infection in pregnant women. The Access HIV Ag/Ab combo assay is for use on the DxI 9000 Access Immunoassay Analyzer only. This assay is not intended for use for screening donors of blood or blood products or human cells, tissues, or cellular or tissue-based products (HCT/Ps).

Device Story

The Access HIV Ag/Ab combo is a paramagnetic particle, chemiluminescent immunoassay performed on the DxI 9000 Access Immunoassay Analyzer. It uses a one-step sandwich assay for HIV-1 p24 antigen and a two-step sandwich assay for HIV-1/HIV-2 antibodies. Input samples (serum/plasma) are mixed with paramagnetic particles coated with anti-HIV-1 p24 antibodies and HIV peptides (groups M, O, and HIV-2). After incubation and magnetic separation of unbound materials, a chemiluminescent substrate is added; light output is measured by a luminometer. The system automatically compares light intensity to a stored calibration curve to provide qualitative results (Reactive/Non-reactive). Used in clinical laboratories by technicians to aid in diagnosing HIV infection. The device provides rapid, automated detection, enabling earlier identification of infection compared to some existing methods, supporting timely clinical decision-making.

Clinical Evidence

Clinical performance evaluated in a multi-center study of 10,254 samples (9,079 prospective, 1,175 retrospective). Specificity was 99.7% (8,439/8,467) in low and high-risk populations. Clinical sensitivity was 100% (1,787/1,787) in known positive subjects. The study included pediatric, adult, and pregnant cohorts. Seroconversion panels showed the device detected HIV 1-2 bleeds earlier than the comparator in 11/30 panels.

Technological Characteristics

Paramagnetic particle, chemiluminescent immunoassay. Materials: recombinant anti-HIV-1 p24 antibody, HIV peptides (groups M, O, HIV-2), monoclonal anti-tag antibody, alkaline phosphatase conjugate. Energy source: luminometer-based light detection. Form factor: liquid, ready-to-use reagent packs for DxI 9000 Access Immunoassay Analyzer. Connectivity: standalone analyzer. Software: automated qualitative assessment via stored calibration.

Indications for Use

Indicated for the qualitative detection and differentiation of HIV-1 p24 antigen and antibodies to HIV-1 (groups M and O) and/or HIV-2 in human serum and plasma. Patient population includes pediatric (ages 2-21) and adult subjects, including pregnant women. Intended as an aid in the diagnosis of HIV-1/HIV-2 infection, including acute or primary HIV-1 infection. Not for blood/tissue donor screening.

Regulatory Classification

Identification

Human immunodeficiency virus (HIV) serological diagnostic and supplemental tests are prescription devices for the qualitative detection of HIV antigen(s) and/or detection of antibodies against HIV in human body fluids or tissues. The tests are intended for use as an aid in the diagnosis of infection with HIV and are for professional use only. The test results are intended to be interpreted in conjunction with other relevant clinical and laboratory findings. These tests are not intended to be used for monitoring patient status, or for screening donors of blood or blood products, or human cells, tissues, and cellular and tissue-based products (HCT/Ps).

Special Controls

*Classification.* Class II (special controls). The special controls for this device are:(1) For all HIV serological diagnostic and supplemental tests (i) The labeling must include: (A) An intended use that states that the device is not intended for use for screening donors of blood or blood products or HCT/Ps. (B) A detailed explanation of the principles of operation and procedures used for performing the assay. (C) A detailed explanation of the interpretation of results and recommended actions to take based on results. (D) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. The limitations must include, but are not limited to, statements that indicate: ( *1* ) The matrices with which the device has been cleared, and that use of this test kit with specimen types other than those specifically cleared for this device may result in inaccurate test results.( *2* ) The test is not intended to be used to monitor individuals who are undergoing treatment for HIV infection.( *3* ) A specimen with a reactive result should be investigated further following current guidelines.( *4* ) All test results should be interpreted in conjunction with the individual's clinical presentation, history, and other laboratory results.( *5* ) A test result that is nonreactive does not exclude the possibility of exposure to or infection with HIV. Nonreactive results in this assay may be due to analyte levels that are below the limit of detection of this assay.(ii) Device verification and validation must include: (A) Detailed device description, including the device components, ancillary reagents required but not provided, and an explanation of the methodology. Additional information appropriate to the technology must be included, such as the amino acid sequence of antigen(s) and design of capture antibodies. (B) For devices with assay calibrators, the design of all primary, secondary, and subsequent quantitation standards used for calibration as well as their traceability to a reference material. In addition, analytical testing must be performed following the release of a new lot of the standard material that was used for device clearance, or when there is a transition to a new calibration standard. (C) Detailed documentation of analytical performance studies conducted as appropriate to the technology, specimen types tested, and intended use of the device, including, but not limited to, limit of blank, limit of detection, cutoff determination, precision, endogenous and exogenous interferences, cross reactivity, carryover, quality control, matrix equivalency, and sample and reagent stability. Samples selected for use in analytical studies or used to prepare samples for use in analytical studies must be from subjects with clinically relevant circulating genotypes in the United States. (D) Multisite reproducibility study that includes the testing of three independent production lots. (E) Analytical sensitivity of the test must be the same as or better than that of other cleared or approved tests. Samples tested must include appropriate numbers and types of samples, including real clinical samples near the lower limit of detection. Analytical specificity of the test must be the same as or better than that of other cleared or approved tests. Samples must include appropriate numbers and types of samples from patients with different underlying illnesses or infections and from patients with potential endogenous interfering substances. (F) Detailed documentation of performance from a multisite clinical study. Performance must be analyzed relative to an FDA-cleared or approved comparator. This study must be conducted using patient samples, with an appropriate number of HIV positive and HIV negative samples in applicable risk categories. Additional subgroups or types must be validated using appropriate numbers and types of samples. The samples may be a combination of fresh and repository samples, sourced from within and outside the United States, as appropriate. The study designs, including number of samples tested, must be sufficient to meet the following criteria: ( *1* ) Clinical sensitivity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 99 percent.( *2* ) Clinical specificity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 99 percent.(G) Strategies for detection of new strains, types, subtypes, genotypes, and genetic mutations as they emerge. (H) Risk analysis and management strategies, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on test performance. (I) Final release criteria to be used for manufactured test lots with appropriate evidence that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims. (J) All stability protocols, including acceptance criteria. (K) Appropriate and acceptable procedure(s) for evaluating customer complaints and other device information that determines when to submit a medical device report. (L) Premarket notification submissions must include the information contained in paragraph (b)(1)(ii)(A) through (K) of this section. (iii) Manufacturers must submit a log of all complaints. The log must include the following information regarding each complaint if available: The type of event ( *e.g.,* false negative/false nonreactive or false positive/false reactive), lot, date, population, and whether or not the complaint was reported under part 803 of this chapter (Medical Device Reporting). The log must be submitted annually on the anniversary of clearance for 5 years following clearance of a traditional premarket notification.(2) If the test is intended for Point of Care (PoC) use, the following special controls, in addition to those listed in paragraph (b)(1) of this section apply: (i) The PoC labeling must include a statement that the test is intended for PoC use. (ii) The PoC labeling must include the following information near the statement of the intended use: (A) That the test is for distribution to clinical laboratories that have an adequate quality assurance program, including planned systematic activities that provide adequate confidence that requirements for quality will be met and where there is assurance that operators will receive and use the instructional materials. (B) That the test is for use only by an agent of a clinical laboratory. (C) Instructions for individuals to receive the “Subject Information Notice” prior to specimen collection and appropriate information when test results are provided. (iii) PoC labeling must include instructions to follow current guidelines for informing the individual of the test result and its interpretation. (iv) The instructions in the labeling must state that reactive results are considered preliminary and should be confirmed following current guidelines. (v) Device verification and validation for PoC use must include: (A) Detailed documentation of performance from a multisite clinical study conducted at appropriate PoC sites. Performance must be analyzed relative to an FDA cleared or approved comparator. This study must be conducted using patient samples, with appropriate numbers of HIV positive and HIV negative samples in applicable risk categories. Additional subgroup or type claims must be validated using appropriate numbers and types of samples. The samples may be a combination of fresh and repository samples, sourced from within and outside the United States, as appropriate. If the test is intended solely for PoC use, the test must meet only the performance criteria in paragraphs (b)(2)(v)(A)( *1* ) and (*2* ) of this section and not the criteria in paragraph (b)(1)(ii)(F) of this section:( *1* ) Clinical sensitivity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 98 percent.( *2* ) Clinical specificity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 98 percent.(B) Premarket notification submissions must include the information contained in paragraph (b)(2)(v)(A) of this section. (3) If the test is intended for supplemental use in addition to use as an aid in initial diagnosis, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, as appropriate, apply: (i) The labeling must include a statement that the test is intended for use as an additional test to confirm the presence of HIV antibodies or antigens in specimens found to be repeatedly reactive by a diagnostic screening test. (ii) Device validation and verification for supplemental use must include a clinical study, including samples that were initially reactive and repeatedly reactive on a diagnostic test but were negative or indeterminate on a different confirmatory test. Premarket notification submissions must include this information. (4) If the test is intended solely as a supplemental test, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, except those in paragraphs (b)(1)(ii)(F) and (b)(2)(v)(A) of this section, as appropriate, apply: (i) The labeling must include a statement that the test is intended for use as an additional test to confirm the presence of HIV antibodies or antigens in specimens found to be repeatedly reactive by a diagnostic screening test. (ii) The labeling must clearly state that the test is not for use for initial diagnosis or is not intended as a first-line test. (iii) Device validation and verification must include a clinical study including samples that were initially reactive and repeatedly reactive on a diagnostic test but were negative or indeterminate on a confirmatory test. Premarket notification submissions must include this information. (5) If the test is intended to differentiate different HIV types, the following special controls, in addition to those listed in paragraphs (b)(1) through (4) of this section, as appropriate, apply: (i) The labeling must include the statement that the test is intended for the confirmation of initial results from a diagnostic test and differentiation of different HIV types. (ii) The results interpretation in the labeling must include instructions for the user on how to interpret the results, including un-typeable and co-infection results. (iii) Device validation and verification must include evaluation of analytical and clinical sensitivity and specificity for each of the HIV types, strains, and subtypes of HIV intended to be differentiated. Premarket notification submissions must include this information.

Predicate Devices

• Abbott ARCHITECT™ HIV Ag/Ab Combo (BP090080)

Submission Summary (Full Text)

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## 510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

**510(k) Number:** BK230833

**Date Prepared:** July 25, 2023

### **Submitter Name and Address:**

Beckman Coulter, Inc
1000 Lake Hazeltine Drive
Chaska, MN 55318

### **Primary Contact:**

Beth Davis
Staff Regulatory Affairs
Email: (b) (6) @beckman.com
Phone: +(1) 800-854-3633

### **Alternate Contact:**

David Ikeda
Principal Regulatory Affairs
Email: (b) (6) @beckman.com
Phone: +(1) 800-854-3633

**Trade Name:** Access HIV Ag/Ab combo, Access HIV Ag/Ab combo Calibrators, & Access HIV Ag/Ab combo QC

**Common Name:** HIV Serological Detection Test System

**Classification Regulation:** 21 CFR 866.3956; 862.1150; 862.1660

**Classification Product Code:** MZF, JIT, MJY, MJX, MJZ

### **Predicate Device:**

Abbott ARCHITECT™ HIV Ag/Ab Combo, BP090080

## Device Description

The Access HIV Ag/Ab combo assay requires Access HIV Ag/Ab combo (reagent packs), Access HIV Ag/Ab combo Calibrators (C1 and C2), and Access HIV Ag/Ab combo QC (QC1-QC5). The assay for HIV-1 p24 antigen detection (HIV-Ag) is a one-step immunoenzymatic “sandwich” assay. Paramagnetic particles (PMP) coated with recombinant anti-HIV-1 p24 antibody, paramagnetic particles coated with three HIV peptides representing HIV-1 group M, HIV-1 group O and HIV-2 antigens, monoclonal anti-HIV-1 p24 antibody conjugated to alkaline phosphatase (ALP), and sample are added to a reaction vessel. HIV-1 p24 present in the patient sample is bound in a “sandwich” complex between the anti-HIV-1 p24 antibody coated on the solid phase and the anti-HIV-1 p24 antibody conjugate. After incubation, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. A chemiluminescent substrate is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is compared to the HIV-1 p24 antigen cutoff value defined during calibration of the instrument. Qualitative assessment of HIV-1 p24 antigen is automatically determined from a stored calibration.

Access HIV Ag/Ab combo 510(k)

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The assay for anti-HIV-1 / anti-HIV-2 antibody (HIV-Ab) Detection is a two-step immunoenzymatic “sandwich” assay. Paramagnetic particles coated with recombinant anti-HIV-1 p24 antibody, paramagnetic particles coated with three HIV peptides representing HIV-1 group M, HIV-1 group O and HIV-2 antigens, monoclonal anti-tag antibody conjugated to alkaline phosphatase, three tagged HIV peptides representing HIV-1 group M, HIV-1 group O and HIV-2 antigens, and sample are added to a reaction vessel. Antibodies to HIV-1 group M, HIV-1 group O or HIV-2 present in the patient sample are bound in a “sandwich” complex between the HIV peptides coated on the solid phase and the tagged HIV peptides/anti-tag conjugate. After incubation, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. The same three tagged HIV peptides and monoclonal anti-tag antibody conjugated to alkaline phosphatase (OVL- overload) are added to the reaction vessel and incubated. After this second incubation, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. A chemiluminescent substrate is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is compared to the antibody cutoff value defined during calibration of the instrument. Qualitative assessment of HIV antibodies is automatically determined from a stored calibration.

The Access HIV Ag/Ab combo Calibrators are used to establish calibration (determine the cutoff value) for the Access HIV Ag/Ab combo assay. By comparing the light intensity generated by a sample to the cutoff value, the presence or absence of human immunodeficiency virus antigen and/or antibodies in the sample is determined. Two calibrators are used with Access HIV Ag/Ab combo assay. Calibrator C1 is dedicated to the Ag analysis, while Calibrator C2 is dedicated to the Ab analysis.

Quality control (QC) materials simulate the characteristics of patient samples and are essential for monitoring the system performance of the Access HIV Ag/Ab combo immunoassays. In addition, they are an integral part of good laboratory practices.

The Access HIV Ag/Ab combo reagents are provided in liquid ready-to-use format designed for optimal performance on the Beckman Coulter DxI 9000 Access Immunoassay Analyzer only. Each reagent kit contains two reagent packs. The calibrator kit and QC kit contain one vial per level. Other items needed to run the assay include Lumi-Phos PRO substrate and UniCel DxI Wash Buffer II.

## Intended Use

The Access HIV Ag/Ab combo assay is a paramagnetic particle, chemiluminescent immunoassay for the simultaneous qualitative in vitro detection and differentiation of HIV-1 p24 antigen and antibodies to HIV-1 (groups M and O) and/or HIV-2 in human pediatric (ages 2 through 21 years) and adult serum and serum separator tubes or plasma [lithium heparin, lithium heparin separator tubes, dipotassium (K₂) EDTA, tripotassium (K₃) EDTA, sodium citrate, acid-citrate-dextrose (ACD) and citrate phosphate-dextrose (CPD)] using the DxI 9000 Access Immunoassay Analyzer.

The Access HIV Ag/Ab combo assay is intended to be used as an aid in the diagnosis of HIV-1 and/or HIV-2 infection, including acute or primary HIV-1 infection. The assay may also be used as an aid in the diagnosis of HIV-1 and/or HIV-2 infection in pregnant women.

The Access HIV Ag/Ab combo assay is for use on the DxI 9000 Access Immunoassay Analyzer only.

This assay is not intended for use for screening donors of blood or blood products or human cells, tissues, or cellular or tissue-based products (HCT/Ps).

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The Access HIV Ag/Ab combo Calibrators are intended to calibrate the Access HIV Ag/Ab combo assay for the simultaneous qualitative detection and differentiation of HIV-1 p24 antigen and antibodies to HIV-1 (groups M and O) and/or HIV-2 in human serum and plasma, using the DxI 9000 Access Immunoassay Analyzer.

The Access HIV Ag/Ab combo QC is intended for monitoring system performance of the Access HIV Ag/Ab combo assay. The Access HIV Ag/Ab combo QC is for use on the DxI 9000 Access Immunoassay Analyzer.

### Comparison Table

| Features / Characteristics | Candidate Device Access HIV Ag/Ab combo | Predicate Device (BP090080) ARCHITECT HIV Ag/Ab Combo | Comment |
| --- | --- | --- | --- |
| Reagent Intended Use and Clinical Indications | The Access HIV Ag/Ab combo assay is a paramagnetic particle, chemiluminescent immunoassay for the simultaneous qualitative *in vitro* detection and differentiation of HIV-1 p24 antigen and antibodies to HIV-1 (groups M and O) and/or HIV-2 in human pediatric (ages 2 through 21 years) and adult serum and serum separator tubes or plasma [lithium heparin, lithium heparin separator tubes, dipotassium (K_{2}) EDTA, tripotassium (K_{3}) EDTA, sodium citrate, acid-citrate-dextrose (ACD) and citrate phosphate-dextrose (CPD)] using the DxI 9000 Access Immunoassay Analyzer. **The Access HIV Ag/Ab combo assay is intended to be used as an aid in the diagnosis of HIV-1 and/or HIV-2 infection, including acute or primary HIV-1 infection. The assay may also be used as an aid in the diagnosis of HIV-1 and/or HIV-2 infection in pregnant women.** The Access HIV Ag/Ab combo assay is for use on the DxI 9000 Access Immunoassay Analyzer only. This assay is not intended for use for screening donors of blood or blood products or human cells, tissues, or cellular or tissue-based products (HCT/Ps). | The ARCHITECT HIV Ag/Ab Combo assay is a chemiluminescent microparticle immunoassay (CMIA) for the simultaneous qualitative detection of human immunodeficiency virus (HIV) p24 antigen and antibodies to HIV type 1 (HIV-1 group M and group O) and/or type 2 (HIV-2) in human serum and plasma (EDTA and heparin). **The ARCHITECT HIV Ag/Ab Combo assay is intended to be used as an aid in the diagnosis of HIV-1/HIV-2 infection, including acute or primary HIV-1 infection. The assay may also be used as an aid in the diagnosis of HIV-1/HIV-2 infection in pediatric subjects (i.e., children as young as two years of age) and in pregnant women.** An ARCHITECT HIV Ag/Ab Combo reactive result does not distinguish between the detection of HIV-1 p24 antigen, HIV-1 antibody, or HIV-2 antibody. The ARCHITECT HIV Ag/Ab Combo assay is not intended for use in screening blood or plasma donors. The effectiveness of ARCHITECT HIV Ag/Ab Combo for use in screening blood or plasma donors has not been established. However, this assay can be used as a blood donor screening assay in urgent situations where traditional licensed blood donor screening tests are unavailable or their use is impractical. | Similar |

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| Features / Characteristics | Candidate Device Access HIV Ag/Ab combo | Predicate Device (BP090080) ARCHITECT HIV Ag/Ab Combo | Comment |
| --- | --- | --- | --- |
| Calibrator Intended Use | The Access HIV Ag/Ab combo Calibrators are intended to calibrate the Access HIV Ag/Ab combo assay for the simultaneous qualitative detection and differentiation of HIV-1 p24 antigen and antibodies to HIV-1 (groups M and O) and/or HIV-2 in human serum and plasma, using the DxI 9000 Access Immunoassay Analyzer. | The ARCHITECT HIV Ag/Ab Combo Calibrator (CAL 1) is for the calibration of the ARCHITECT / System when the system is used for the simultaneous qualitative detection of human immunodeficiency virus (HIV) p24 antigen and antibodies to HIV type 1 (HIV-1 group M and group O) and/or type 2 (HIV-2) in human serum or plasma using the ARCHITECT HIV Ag/Ab Combo assay. The performance of the ARCHITECT HIV Ag/Ab Combo Calibrator has not been established with any other HIV assay. | Similar |
| QC Intended Use | The Access HIV Ag/Ab combo QC is intended for monitoring system performance of the Access HIV Ag/Ab combo assay. The Access HIV Ag/Ab combo QC is for use on the DxI 9000 Access Immunoassay Analyzer. | The ARCHITECT HIV Ag/Ab Combo Controls (CONTROL –, CONTROL + 1, CONTROL + 2, CONTROL + 3, CONTROL + 4) are used for monitoring the performance of the ARCHITECT / System (reagents, calibrator, and instrument) when used for the simultaneous qualitative detection of human immunodeficiency virus (HIV) p24 antigen and antibodies to HIV type 1 (HIV-1 group M and group O) and/or type 2 (HIV-2) in human serum or plasma using the ARCHITECT HIV Ag/Ab Combo assay. | Similar |
| Environment of Use | Health Care Providers requesting samples to be tested by clinical laboratory technicians | Same | N/A |
| Operating Principle | Sandwich immunoassay technology | Same | N/A |
| Analyte Measured | HIV-1 p24 antigen and antibodies to HIV-1 (groups M and O) and/or HIV-2 | Same | N/A |
| Antibody and Antigen sources | Monoclonal (mouse) anti-tag antibody Monoclonal (mouse) anti-HIV-1 p24 antibody Histamine tagged HIV peptides representing HIV-1 group M, HIV-1 group O and HIV-2 antigens | Acridinium-labeled HIV-1 antigens, acridinium-labeled HIV-1/HIV-2 synthetic peptides, and acridinium-labeled HIV p24 antibody (mouse IgG, monoclonal) | Different |
| Assay Type | HIV-1 p24 antigen detection (HIV-Ag) Assay type: one-step immunoenzymatic 'sandwich' assay Anti-HIV-1 / anti-HIV-2 antibody detection (HIV-Ab) Assay type: two-step immunoenzymatic 'sandwich' assay | Two-step immunoassay to determine the presence of HIV-1 p24 antigen, antibodies to HIV-1 (group M and group O), and antibodies to HIV-2 | Different |
| Detection Method | Automated, Chemiluminescence | Same | N/A |
| Reagent, Calibrator, and QC format | Liquid, ready to use | Same | N/A |
| Calibrator(s) | 2 | 1 | Different |

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| Features / Characteristics | Candidate Device Access HIV Ag/Ab combo | Predicate Device (BP090080) ARCHITECT HIV Ag/Ab Combo | Comment |
| --- | --- | --- | --- |
| Standardization | HIV-1 p24 antigen detection (HIV-Ag) has been standardized against the WHO International Standard HIV-1 p24 Antigen, NIBSC (National Institute for Biological Standards and Control) code 90/636. | The ARCHITECT HIV Ag/Ab Combo Calibrator 1 is standardized to the Agence française de sécurité sanitaire des produits de santé (AFSSAPS) HIV-1 p24 antigen 50 pg/mL international standard. | Different |
| Traceability | The Access HIV Ag/Ab combo Calibrator (C1) is traceable to manufacturer's internal reference materials. There is no internationally recognized standard for HIV-1 or HIV-2 specific antibody. The Access HIV Ag/Ab combo Calibrator (C2) is traceable to the manufacturer's internal reference materials. Traceability process is based on EN ISO 17511. | Unknown | Different |
| Sample Type | Serum and Plasma | Same | N/A |
| Compatible Anticoagulants | Serum Serum and serum separator tube Plasma Lithium Heparin Lithium Heparin separator tube Dipotassium (K₂) EDTA Tripotassium (K₃) EDTA Sodium Citrate Acid Citrate Dextrose (ACD) Citrate Phosphate Dextrose (CPD) | Serum Serum and serum separator tube Plasma Lithium Heparin with gel separator Sodium heparin Dipotassium (K₂) EDTA Dipotassium (K₃) EDTA with gel separator Tripotassium (K₃) EDTA Disodium (Na₂) EDTA | Different |
| Sample Volume | 60 μL | 150 μL | Different |
| Instrumentation | Dxl 9000 Access Immunoassay Analyzer | ARCHITECT i System | Different |
| Test Result Reporting | Reactive, Non-reactive and S/CO | Reactive, Non-reactive and S/CO | Similar |
| Imprecision | The assay was designed to have within-laboratory imprecision as listed below: • ≤ 0.100 S/CO SD for samples with S/CO < 1.00 • ≤ 10.0% CV for samples with S/CO ≥ 1.00 | Within-Laboratory (Total) CV of ≤ 10% for positive controls and for reactive samples with S/CO ≤ 4, and a Within-Laboratory (Total) CV of ≤ 15% for samples with S/CO >4. | Different |
| Time to Result | ~ 30 minutes | ~ 29 minutes | Similar |
| Reagent Storage and Stability | Unopened at 2 to 10°C up to stated expiration date | Unopened at 2 to 8°C up to stated expiration date | Similar |
| Reagent On-board Stability | 56 Days | 30 days | Different |
| Calibration Frequency | 56 Days | 30 days | Different |
| Calibrator Open Vial | 180 Days | When stored and handled as directed, the calibrator is stable until the expiration date. | Different |
| Control Levels | 5 Levels (1 Negative and 4 Positive for Analyte Measured) | 5 Levels (1 Negative and 4 Positive for Analyte Measured) | Similar |
| Control Matrix | QC1, 2,4 &5 = Human serum based QC3 = Buffer & protein based | Negative QC, QC1, 2,4 = Human serum based QC3 = Buffer & protein based | Similar |
| Control Open Vial | 90 Days | When stored and handled as directed, the controls are stable until the expiration date. | Different |

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## Summary of Studies

### Within-Laboratory Imprecision

The imprecision/reproducibility of the Access HIV Ag/Ab combo assay was evaluated in a study based on CLSI guidance EP05-A3, *Evaluation of Precision of Quantitative Measurement Procedures*. A sixteen-member panel of patient samples for HIV antibody and an eight-member panel of patient samples for HIV antigen, including serum (S), plasma (P), and Access HIV Ag/Ab combo QC samples were assayed in duplicate in two runs per day over a minimum of 20 days. Three lots of Access HIV Ag/Ab combo reagent and calibrator were tested on three DxI 9000 Access Immunoassay Analyzers for the study (one lot per instrument). The combined results for all three lots are presented in the following within-laboratory imprecision tables.

### HIV Antibody Within-Laboratory Imprecision

| Sample | Analyte | N | Mean S/CO | Between Lot & Instrument | | Between-Day | | Between-Run | | Within-Run | | Within-Laboratory (Total) | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | SD (S/CO) | %CV | SD (S/CO) | %CV | SD (S/CO) | %CV | SD (S/CO) | %CV | SD (S/CO) | %CV |
| QC1 | None | 240 | 0.05 | 0.009 | N/A | 0.000 | N/A | 0.007 | N/A | 0.004 | N/A | 0.013 | N/A |
| QC2 | HIV-1 Ab | 240 | 2.68 | 0.125 | 4.7 | 0.045 | 1.7 | 0.055 | 2.0 | 0.053 | 2.0 | 0.153 | 5.7 |
| QC4 | HIV-2 Ab | 240 | 2.54 | 0.288 | 11.3 | 0.038 | 1.5 | 0.067 | 2.6 | 0.058 | 2.3 | 0.304 | 11.9 |
| QC5 | HIV-1O Ab | 240 | 3.53 | 0.656 | 18.6 | 0.089 | 2.5 | 0.070 | 2.0 | 0.073 | 2.1 | 0.670 | 19.0 |
| S1 | None | 240 | 0.05 | 0.009 | N/A | 0.002 | N/A | 0.007 | N/A | 0.004 | N/A | 0.012 | N/A |
| S2 | HIV-1M Ab | 240 | 0.77 | 0.019 | 2.5 | 0.012 | 1.6 | 0.016 | 2.1 | 0.017 | 2.3 | 0.032 | 4.2 |
| S4 | HIV-1M Ab | 240 | 1.18 | 0.035 | 2.9 | 0.019 | 1.6 | 0.029 | 2.5 | 0.024 | 2.0 | 0.055 | 4.6 |
| S5 | HIV-1M Ab | 240 | 3.46 | 0.122 | 3.5 | 0.060 | 1.7 | 0.061 | 1.8 | 0.075 | 2.2 | 0.167 | 4.8 |
| P1 | HIV-1M Ab | 240 | 0.80 | 0.024 | 3.0 | 0.018 | 2.2 | 0.016 | 2.0 | 0.017 | 2.1 | 0.038 | 4.7 |
| P3 | HIV-1M Ab | 240 | 1.10 | 0.033 | 2.9 | 0.018 | 1.7 | 0.025 | 2.3 | 0.026 | 2.3 | 0.052 | 4.7 |
| S6 | HIV-1O Ab | 240 | 1.17 | 0.119 | 10.2 | 0.017 | 1.5 | 0.026 | 2.2 | 0.024 | 2.0 | 0.125 | 10.7 |
| S7 | HIV-1O Ab | 240 | 3.25 | 0.161 | 5.0 | 0.047 | 1.5 | 0.068 | 2.1 | 0.074 | 2.3 | 0.195 | 6.0 |
| P4 | HIV-1O Ab | 240 | 1.24 | 0.098 | 7.9 | 0.022 | 1.8 | 0.030 | 2.4 | 0.025 | 2.0 | 0.108 | 8.7 |
| S8 | HIV-2 Ab | 240 | 1.22 | 0.102 | 8.4 | 0.013 | 1.1 | 0.038 | 3.1 | 0.035 | 2.9 | 0.115 | 9.4 |
| S9 | HIV-2 Ab | 240 | 3.41 | 0.238 | 7.0 | 0.084 | 2.5 | 0.074 | 2.2 | 0.094 | 2.7 | 0.279 | 8.2 |
| P5 | HIV-2 Ab | 240 | 1.26 | 0.091 | 7.2 | 0.027 | 2.1 | 0.027 | 2.2 | 0.033 | 2.6 | 0.104 | 8.2 |

Note: %CV are not meaningful when S/CO approaches zero. Results are noted as N/A.

### HIV-1 p24 Antigen Within-Laboratory Imprecision

| Sample | Analyte | N | Mean S/CO | Between Lot & Instrument | | Between-Day | | Between-Run | | Within-Run | | Within-Laboratory (Total) | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | SD (S/CO) | %CV | SD (S/CO) | %CV | SD (S/CO) | %CV | SD (S/CO) | %CV | SD (S/CO) | %CV |
| P2 | HIV-1 p24 | 240 | 0.91 | 0.043 | 4.7 | 0.012 | 1.4 | 0.013 | 1.4 | 0.014 | 1.6 | 0.049 | 5.4 |
| P6 | HIV-1 p24 | 240 | 1.24 | 0.059 | 4.8 | 0.016 | 1.3 | 0.021 | 1.7 | 0.027 | 2.1 | 0.070 | 5.7 |
| QC1 | None | 240 | 0.14 | 0.012 | N/A | 0.007 | N/A | 0.003 | N/A | 0.009 | N/A | 0.017 | N/A |
| QC3 | HIV-1p24 | 240 | 3.07 | 0.078 | 2.5 | 0.054 | 1.7 | 0.044 | 1.4 | 0.038 | 1.2 | 0.111 | 3.6 |
| S1 | None | 240 | 0.16 | 0.013 | N/A | 0.005 | N/A | 0.005 | N/A | 0.007 | N/A | 0.016 | N/A |
| S10 | HIV-1 p24 | 240 | 1.12 | 0.047 | 4.2 | 0.015 | 1.4 | 0.018 | 1.7 | 0.017 | 1.5 | 0.056 | 5.0 |
| S11 | HIV-1 p24 | 240 | 3.83 | 0.186 | 4.9 | 0.045 | 1.2 | 0.061 | 1.6 | 0.060 | 1.6 | 0.210 | 5.5 |
| S3 | HIV-1 p24 | 240 | 0.83 | 0.043 | 5.2 | 0.016 | 2.0 | 0.012 | 1.4 | 0.018 | 2.2 | 0.051 | 6.1 |

Note: %CV are not meaningful when S/CO approaches zero. Results are noted as N/A.

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Another study was performed to estimate variance components for the Access HIV Ag/Ab combo assay including instrument, reagent lots, between-day, between-run and within-run, using three instruments and three reagent lots. Overall variance by analyte for Access HIV Ag/Ab combo is within the expected reproducibility performance of the assay. The HIV Ag analysis variance was assessed across three reagent pack lots, over three days and two runs per day. For HIV Ab analysis variance was assessed across three reagent pack lots, over six days, with one run per day.

### HIV Antibody Variance

| Sample ID | Analyte | Mean S/CO | n | CV or SD Instrument (S/CO) | CV or SD Reagent Lot (S/CO) | CV or SD Reproducibility (S/CO) |
| --- | --- | --- | --- | --- | --- | --- |
| QC1 Lot1 | None | 0.062 | 162 | 0.006 | 0.011 | 0.017 |
| QC1 Lot2 | None | 0.057 | 161 | 0.005 | 0.009 | 0.015 |
| QC1 Lot3 | None | 0.065 | 162 | 0.006 | 0.010 | 0.018 |
| QC2 Lot1 | HIV-1 M | 2.823 | 162 | 2.0% | 3.7% | 5.5% |
| QC2 Lot2 | HIV-1 M | 2.832 | 162 | 2.3% | 3.7% | 6.2% |
| QC2 Lot3 | HIV-1 M | 3.068 | 161 | 1.6% | 1.3% | 5.7% |
| QC4 Lot1 | HIV-2 | 2.606 | 162 | 3.1% | 7.1% | 8.9% |
| QC4 Lot2 | HIV-2 | 2.740 | 162 | 2.6% | 6.9% | 8.6% |
| QC4 Lot3 | HIV-2 | 2.798 | 162 | 2.0% | 7.0% | 8.2% |
| QC5 Lot1 | HIV-1 O | 3.491 | 162 | 2.2% | 11.8% | 12.8% |
| QC5 Lot2 | HIV-1 O | 3.493 | 162 | 2.0% | 11.7% | 12.5% |
| QC5 Lot3 | HIV-1 O | 3.750 | 162 | 1.8% | 12.7% | 13.5% |
| P3 | HIV-1 M | 1.199 | 162 | 1.4% | 2.4% | 5.7% |
| P4 | HIV-1 O | 1.313 | 162 | 1.9% | 4.7% | 6.1% |
| P5 | HIV-2 | 1.333 | 162 | 3.7% | 3.0% | 6.9% |
| P7 | HIV-1 M | 3.848 | 162 | 2.5% | 2.8% | 5.3% |
| P8 | HIV-1 M | 10.359 | 162 | 2.2% | 3.0% | 5.1% |
| S1 | None | 0.067 | 162 | 0.006 | 0.010 | 0.017 |
| S12 | HIV-1 M | 39.089 | 162 | 1.8% | 3.2% | 5.4% |
| S13 | HIV-1 M | 132.268 | 162 | 2.4% | 3.2% | 5.4% |
| S14 | HIV-1 M | 197.292 | 162 | 2.7% | 3.7% | 5.7% |
| S15 | None | 0.064 | 162 | 0.004 | 0.010 | 0.015 |
| S2 | HIV-1 M | 0.832 | 162 | 0.013 | 0.012 | 0.047 |
| S4 | HIV-1 M | 1.267 | 161 | 2.7% | 2.8% | 6.4% |
| S5 | HIV-1 M | 5.760 | 162 | 3.3% | 5.4% | 7.3% |
| S6 | HIV-1 O | 1.239 | 162 | 1.1% | 6.2% | 7.2% |
| S7 | HIV-1 O | 10.769 | 161 | 2.3% | 5.6% | 7.1% |
| S8 | HIV-2 | 1.279 | 162 | 3.3% | 4.4% | 7.5% |
| S9 | HIV-2 | 7.592 | 161 | 4.3% | 5.2% | 8.5% |

### HIV-1 p24 Antigen Variance

| Sample ID | Analyte | Mean S/CO | n | CV or SD Instrument (S/CO) | CV or SD Reagent Lot (S/CO) | CV or SD Reproducibility (S/CO) |
| --- | --- | --- | --- | --- | --- | --- |
| PS1 | None | 0.163 | 162 | 0.004 | 0.010 | 0.013 |
| QC1 Lot1 | None | 0.150 | 162 | 0.004 | 0.011 | 0.013 |
| QC1 Lot2 | None | 0.151 | 162 | 0.004 | 0.011 | 0.014 |
| QC1 Lot3 | None | 0.161 | 162 | 0.005 | 0.010 | 0.013 |
| S15 | None | 0.154 | 162 | 0.003 | 0.011 | 0.014 |
| P6 | p24 Ag | 1.284 | 161 | 1.5% | 2.6% | 4.3% |
| PS18 | p24 Ag | 4.543 | 162 | 0.6% | 3.4% | 4.4% |
| S10 | p24 Ag | 1.160 | 162 | 1.4% | 2.2% | 4.0% |
| S16 | p24 Ag | 144.418 | 162 | 1.3% | 1.7% | 3.9% |
| S3 | p24 Ag | 0.865 | 161 | 0.009 | 0.029 | 0.042 |
| QC3 Lot1 | p24 Ag | 3.003 | 162 | 1.1% | 2.1% | 3.7% |
| QC3 Lot2 | p24 Ag | 3.040 | 162 | 1.5% | 2.4% | 4.7% |
| QC3 Lot3 | p24 Ag | 3.078 | 162 | 0.9% | 2.1% | 4.0% |

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## Reproducibility

A 5-day reproducibility study was performed on the DxI 9000 Access Immunoassay analyzer based on CLSI guideline EP05-A3, *Evaluation of Precision of Quantitative Measurement Procedures*. A sixteen-member panel of patient samples for HIV antibody and an eight-member panel of patient samples for HIV antigen, including serum (S), plasma (P), and Access HIV Ag/Ab combo QC samples were assayed on three instruments at three different clinical sites, using one lot of Access HIV Ag/Ab combo reagent and calibrator. Each panel member was assayed in replicates of three at two separate times per day.

### HIV Antibody Reproducibility

| Sample | N | Mean (S/CO) | Between-Site | | Between-Day | | Between-Run | | Repeatability (Within-Run) | | Reproducibility | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | SD (S/CO) | %CV | SD (S/CO) | %CV | SD (S/CO) | %CV | SD (S/CO) | %CV | SD (S/CO) | %CV |
| S1 | 90 | 0.06 | 0.003 | N/A | 0.004 | N/A | 0.001 | N/A | 0.005 | N/A | 0.007 | N/A |
| S2 | 90 | 0.86 | 0.062 | 7.2 | 0.000 | 0.0 | 0.019 | 2.2 | 0.022 | 2.6 | 0.068 | 8.0 |
| S4 | 90 | 1.30 | 0.097 | 7.4 | 0.000 | 0.0 | 0.015 | 1.2 | 0.036 | 2.7 | 0.105 | 8.0 |
| S5 | 90 | 3.84 | 0.249 | 6.5 | 0.054 | 1.4 | 0.073 | 1.9 | 0.104 | 2.7 | 0.285 | 7.4 |
| S6 | 90 | 1.39 | 0.114 | 8.2 | 0.000 | 0.0 | 0.021 | 1.5 | 0.030 | 2.2 | 0.120 | 8.6 |
| S7 | 90 | 3.57 | 0.272 | 7.6 | 0.027 | 0.7 | 0.029 | 0.8 | 0.070 | 2.0 | 0.283 | 7.9 |
| S8 | 90 | 1.39 | 0.108 | 7.8 | 0.028 | 2.0 | 0.035 | 2.5 | 0.048 | 3.5 | 0.127 | 9.1 |
| S9 | 90 | 3.84 | 0.338 | 8.8 | 0.093 | 2.4 | 0.050 | 1.3 | 0.126 | 3.3 | 0.376 | 9.8 |
| P1 | 90 | 0.85 | 0.059 | 6.9 | 0.013 | 1.5 | 0.013 | 1.5 | 0.022 | 2.6 | 0.065 | 7.7 |
| P3 | 90 | 1.20 | 0.090 | 7.5 | 0.023 | 1.9 | 0.024 | 2.0 | 0.038 | 3.1 | 0.103 | 8.5 |
| P4 | 90 | 1.21 | 0.081 | 6.7 | 0.012 | 1.0 | 0.016 | 1.4 | 0.035 | 2.9 | 0.090 | 7.5 |
| P5 | 90 | 1.06 | 0.101 | 9.5 | 0.022 | 2.1 | 0.011 | 1.0 | 0.040 | 3.8 | 0.111 | 10.5 |
| QC1 (negative) | 90 | 0.05 | 0.002 | N/A | 0.001 | N/A | 0.000 | N/A | 0.010 | N/A | 0.010 | N/A |
| QC2 (HIV-1 Ab) | 90 | 3.15 | 0.201 | 6.4 | 0.074 | 2.3 | 0.000 | 0.0 | 0.093 | 2.9 | 0.234 | 7.4 |
| QC4 (HIV-2 Ab) | 90 | 3.17 | 0.251 | 7.9 | 0.000 | 0.0 | 0.133 | 4.2 | 0.147 | 4.6 | 0.320 | 10.1 |
| QC5 (HIV-1 group O Ab) | 90 | 4.63 | 0.324 | 7.0 | 0.104 | 2.2 | 0.120 | 2.6 | 0.158 | 3.4 | 0.394 | 8.5 |

Note: %CV are not meaningful when S/CO approaches zero. Results are noted as N/A.

### HIV-1 p24 Antigen Reproducibility

| Sample | N | Mean (S/CO) | Between-Site | | Between-Day | | Between-Run | | Repeatability (Within-Run) | | Reproducibility | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | SD (S/CO) | %CV | SD (S/CO) | %CV | SD (S/CO) | %CV | SD (S/CO) | %CV | SD (S/CO) | %CV |
| S1 | 90 | 0.17 | 0.002 | N/A | 0.003 | N/A | 0.005 | N/A | 0.010 | N/A | 0.012 | N/A |
| S3 | 90 | 0.85 | 0.008 | 0.9 | 0.011 | 1.3 | 0.013 | 1.6 | 0.016 | 1.9 | 0.025 | 2.9 |
| S10 | 90 | 1.12 | 0.022 | 2.0 | 0.010 | 0.9 | 0.015 | 1.3 | 0.019 | 1.7 | 0.034 | 3.0 |
| S11 | 90 | 3.79 | 0.085 | 2.2 | 0.000 | 0.0 | 0.049 | 1.3 | 0.059 | 1.6 | 0.114 | 3.0 |
| P2 | 90 | 0.97 | 0.017 | 1.7 | 0.016 | 1.6 | 0.006 | 0.6 | 0.018 | 1.9 | 0.030 | 3.1 |
| P6 | 90 | 1.24 | 0.026 | 2.1 | 0.014 | 1.1 | 0.012 | 1.0 | 0.024 | 1.9 | 0.040 | 3.2 |
| QC1 (negative) | 90 | 0.16 | 0.000 | N/A | 0.002 | N/A | 0.000 | N/A | 0.010 | N/A | 0.010 | N/A |
| QC3 (HIV-1 p24 Ag) | 90 | 3.02 | 0.031 | 1.0 | 0.000 | 0.0 | 0.030 | 1.0 | 0.051 | 1.7 | 0.067 | 2.2 |

Note: %CV are not meaningful when S/CO approaches zero. Results are noted as N/A.

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### Limit of Blank (LoB) and Limit of Detection (LoD)

LoB and LoD studies were conducted on the DxI 9000 Access Immunoassay Analyzer following methods described in CLSI guideline EP17-A2:2012, *Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures*. LoB was calculated separately for two reagent lots for both serum and plasma using the non-parametric method. The maximum LoB estimates were carried forward in the Limit of Detection (LoD) calculation where precision profile models relating standard deviation and mean S/CO for each sample and reagent lot were used to estimate the LoD. The maximum observed LoB and LoD results for both HIV-1 p24 antigen and HIV antibody are shown in the following table:

| | Limit of Blank (LoB) S/CO | Limit of Detection (LoD) S/CO |
| --- | --- | --- |
| HIV-1 p24 antigen (serum) | 0.28 | 0.30 |
| HIV-1 p24 antigen (plasma) | 0.18 | 0.19 |
| HIV antibody (serum) | 0.08 | 0.10 |
| HIV antibody (plasma) | 0.11 | 0.13 |

### Matrix Comparison

A matrix comparison study established the equivalence of serum and plasma specimens using the Access HIV Ag/Ab combo assay on the DxI 9000 Access Immunoassay Analyzer. The study was performed using a protocol based on CLSI guideline EP09C, 3rd Edition, *Method Comparison and Bias Estimation Using Patient Samples*. Matched donor sets consisting of nine specimen types each were evaluated. Fifty samples were evaluated with the HIV Ag assessment for each sample type. Fifty-three samples were evaluated with the HIV Ab assessment for each sample type. Serum served as the reference tube type. A Passing-Bablok regression analysis (using the mean test sample results versus the mean reference results) was completed for each matrix to determine the regression equation, slope with bootstrap 95% confidence intervals, and the correlation coefficient (r).

The Access HIV Ag/Ab combo assay demonstrated sample type equivalence between serum (no gel) and eight serum/plasma matrices. Passing Bablok regression slopes ranged from 0.90 to 1.00 for the HIV Ag assessment and 0.98 to 1.04 for the HIV Ab assessment.

The Access HIV Ag/Ab combo assay detects HIV Ag and Ab in the following matrices.

| Sample Type |
| --- |
| Serum (Reference) |
| Serum Separator Tube |
| Plasma Lithium Heparin |
| Plasma Lithium Heparin Separator Tube |
| Plasma K_{2} EDTA |
| Plasma K_{3} EDTA |
| Plasma Sodium Citrate |
| Plasma Acid Citrate Dextrose (ACD) |
| Plasma Citrate Phosphate Dextrose (CPD) |

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## Sample Stability

### Sample Handling Stability

Sample handling and freeze/thaw stability was established for the Access HIV Ag/Ab combo assay on the DxI 9000 Access Immunoassay Analyzer. The study is based on CLSI guideline GP44-A4, *Procedures for the Handling and Processing of Blood* & CLSI guideline EP25-A. *Evaluation of Stability of In Vitro Diagnostic Reagents*. The mean S/CO bias for stressed vs. unstressed samples was within $\pm 0.150$ for negative samples, and the mean S/CO percentage bias for stressed vs. unstressed samples was within $\pm 15.0\%$ for positive samples. The study verified the following sample handling claims:

72 hours at 20-25°C,
7 days at 2-8°C,
30 days at $\leq -20^{\circ}\text{C}$ ,
and up to 5 Freeze/Thaw cycles.

### Fresh vs Frozen Sample Stability

A fresh vs frozen sample equivalency study was also performed to evaluate the equivalency between fresh samples (never frozen) and frozen samples after storage at $\leq -18^{\circ}\text{C}$ for at least 16 hours with the Access HIV Ag/Ab combo assay on the DxI 9000 Access Immunoassay Analyzer.

Fresh and frozen samples demonstrated equivalency using the Access HIV Ag/Ab combo assay.

### Fresh vs Frozen Samples Regression Analysis Results

| | n | All Samples Combined Slope | n | Reactive Samples Slope |
| --- | --- | --- | --- | --- |
| Ag | 46 | 1.00 | 31 | 0.99 |
| Ab | 51 | 1.00 | 34 | 1.01 |

## Reagent Stability

### Reagent Shelf-life

Access HIV Ag/Ab combo shelf-life dating was established based on real time stability (RTS) studies for the Access HIV Ag/Ab combo reagent pack. The study was performed to verify the stability at the recommended storage condition (2-10°C), using a protocol based on CLSI guideline EP25-A. The study also included evaluation of reagent pack stability following simulated winter and summer transport stresses of the reagent packs.

The results from the Access HIV Ag/Ab combo reagent pack shelf-life study show that the packs are stable for 365 days at the recommended storage condition of 2-10°C.

### Reagent In-use Stability (Open Pack)

Reagent open pack stability of the Access HIV Ag/Ab combo assay was evaluated at the recommended open storage conditions (2-10°C) using a protocol based on CLSI guideline EP25-A. The study also included evaluation of open pack stability following simulated winter and summer transport stresses of the reagent packs.

The Access HIV Ag/Ab combo reagent pack is stable after opening for up to 56 days when stored at 2-10°C.

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#### Stored Curve Calibration Stability

Access HIV Ag/Ab combo assay stored curve calibration stability was verified on the DxI 9000 Access Immunoassay Analyzer. The evaluation was performed using a protocol based on CLSI guideline EP25-A. The study also included evaluation of calibration stability following simulated winter and summer transport stresses of the reagent packs.

Access HIV Ag/Ab combo stored calibration stability is 56 days.

#### **Calibrator Stability**

##### Calibrator Shelf-life

Access HIV Ag/Ab combo Calibrators shelf-life dating was established based on real time stability (RTS) studies for the Access HIV Ag/Ab combo Calibrators. The study was performed to verify stability at the recommended storage condition (2-10°C), using a protocol based on CLSI guideline EP25-A. The study also included evaluation of calibrator stability following simulated winter and summer transport stresses of the vials.

The final shelf-life dating for the Access HIV Ag/Ab combo Calibrators is 298 days, which reflects the minimum achieved stability duration across the three lots tested.

##### Calibrator In-use Stability (Open Vial)

Open vial stability of the Access HIV Ag/Ab combo Calibrators on the DxI 9000 Access Immunoassay Analyzer was evaluated at the recommended open vial storage conditions (2-10°C) using a protocol based on CLSI guideline EP25-A. The study also included evaluation of calibrator open vial stability following simulated winter and summer transport stresses of the vials.

Access HIV Ag/Ab combo Calibrators are stable when stored at 2-10°C for 180 days after initial use.

#### **QC Stability**

##### QC Shelf-life

Access HIV Ag/Ab combo QC shelf-life dating was established based on real time stability (RTS) studies for the Access HIV Ag/Ab combo QC (QC1 – QC5). The study was performed to verify the stability at the recommended storage condition (2-10°C), using a protocol based on CLSI guideline EP25-A. The study also included evaluation of QC stability following simulated winter and summer transport stresses of the vials.

The final shelf-life dating for the Access HIV Ag/Ab combo QC is 339 days, which reflects the minimum achieved stability duration across the three lots tested.

##### QC In-use Stability (Open Vial)

Open vial stability of the Access HIV Ag/Ab combo QC on the DxI 9000 Access Immunoassay Analyzer was evaluated at the recommended open vial storage conditions (2-10°C) using a protocol based on CLSI guideline EP25-A. The study also included evaluation of QC open vial stability following simulated winter and summer transport stresses of the vials.

The Access HIV Ag/Ab combo QC are stable when stored at 2-10°C for 90 days after initial use.

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## Analytical Sensitivity

### Antigen Detection

The analytical sensitivity of the Access HIV Ag/Ab combo assay for HIV-1 p24 antigen was designed to be less than or equal to 2.00 IU/mL using the WHO International Standard HIV-1 p24 Antigen NIBSC (National Institute for Biological Standards and Controls) code: 90/636.

To examine the analytical sensitivity of the Access HIV Ag/Ab combo assay on the DxI 9000 Access Immunoassay Analyzer, a series of dilutions was prepared in serum and plasma samples using the WHO IS 90/636 to target HIV-1 p24 antigen concentrations in the range of 0.10 – 1.00 IU/mL. The dilutions were assayed using three reagent pack lots and three calibrator lots on two DxI 9000 Access Immunoassay analyzers over three days. The analytical sensitivity for each reagent/calibrator lot combination was determined using a linear fit regression of the S/CO versus the WHO IS 90/636 concentrations (IU/mL). The point estimate of the WHO IS concentration corresponding to S/CO = 1.00 and the 95% CI were used in the analytical sensitivity estimation. The maximum overall analytical sensitivity result determined in this study is summarized in the following table:

| Standard | Analytical Sensitivity |
| --- | --- |
| WHO International Standard HIV-1 p24 Antigen NIBSC code: 90/636. | 0.22 IU/mL (1.66 pg/mL*) |

*Conversion from IU/mL to pg/mL of HIV-1 p24 Ag using WHO calibration curve tested on VIDAS® HIV p24 II assay. VIDAS® is a registered trademark of bioMérieux, SA.

### Antibody Detection

There is no internationally recognized standard for HIV-1 or HIV-2 specific antibody.

## Intra-Assay Carryover

Testing was conducted to assess the HIV antigen (Ag) and HIV antibody (Ab) sample-to-sample and sample-to-reagent pack carryover on the Access HIV Ag/Ab combo assay. Test procedures were based on the guidance document, CLSI guideline EP10-A3, *Preliminary Evaluation of Quantitative Clinical Laboratory Measurement Procedures*.

No intra-assay carryover was observed with the Access HIV Ag/Ab combo assay tested on the DxI 9000 Access Immunoassay Analyzer.

## Hook Effect

A hook study was performed to evaluate whether high levels of analyte in patient specimens result in a hook effect that changes the reported results of the Access HIV Ag/Ab combo assay on the DxI 9000 Access Immunoassay Analyzer.

For the HIV antibody assessment, there were no changes to the interpretation of the results on three reagent pack lots. For the HIV-1 p24 antigen assessment (up to 1 µg/mL), there were no changes to the interpretation of the results, on three reagent pack lots.

No false negative results due to high-dose hook effect were observed with the Access HIV Ag/Ab combo assay.

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# Interfering Substances

The Access HIV Ag/Ab combo assay was evaluated for interference consistent with CLSI guideline EP07 3rd Edition, Interference Testing in Clinical Chemistry. Testing was performed using serum samples containing high negative and low positive levels of HIV-1 p24 antigen and HIV-1 antibodies, spiked with potential interferents, at the concentrations indicated. Of the compounds tested, none were found to cause significant interference using the highest test concentrations indicated in the following table.

| Potential Interferent | Highest Concentration Added |
| --- | --- |
| Hemoglobin | 500 mg/dL |
| Total Protein | 15 g/dL |
| Gamma Globulin | 20 g/L |
| Bilirubin conjugated | 43 mg/dL |
| Bilirubin unconjugated | 43 mg/dL |
| Triglycerides Intralipid | 2,000 mg/dL |
| Biotin | 3,510 ng/mL |
| Aspirin (Acetylsalicylic Acid) | 167 μmol/L |
| Salicylic Acid | 207 μmol/L |
| Acetaminophen (Paracetamol) | 1,030 μmol/L |
| Ibuprofen | 1,060 μmol/L |
| Atorvastatin | 1.34 μmol/L |
| Lisinopril | 0.607 μmol/L |
| Levothyroxine | 0.552 μmol/L |
| Metformin | 92.9 μmol/L |
| Amlodipine | 0.183 μmol/L |
| Omeprazole | 24.3 μmol/L |
| Sertraline | 3.03 μmol/L |

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## Cross Reactivity

Cross-reactivity was evaluated by testing 290 samples for potentially cross-reacting conditions. For preparation of bacterial samples, negative samples were spiked with bacteria (10$^{5}$ CFU/mL) prior to evaluation. No cross-reactivity was observed. The results are summarized in the following table:

| Category | Number of samples tested | Number of reactive samples | Number of nonreactive samples |
| --- | --- | --- | --- |
| Epstein-Barr virus (EBV) | 10 | 0 | 10 |
| Cytomegalovirus (CMV) | 10 | 0 | 10 |
| Herpes simplex virus (HSV1/2) | 10 | 0 | 10 |
| Varicella-zoster virus (VZV) | 10 | 0 | 10 |
| Human T-cell Lymphotropic Virus (HTLV I & II) | 10 | 0 | 10 |
| Hepatitis A Virus (HAV) | 10 | 0 | 10 |
| Hepatitis B Virus (HBV) | 10 | 0 | 10 |
| Hepatitis C virus (HCV) | 10 | 0 | 10 |
| Syphilis | 10 | 0 | 10 |
| Toxoplasmosis | 10 | 0 | 10 |
| *anti-E. coli* (including *E. coli* urinary infection) | 10 | 0 | 10 |
| Influenza post-vaccination | 10 | 0 | 10 |
| Rheumatoid Factor | 10 | 0 | 10 |
| HAMA | 10 | 0 | 10 |
| Anti-Nuclear Antibody (ANA) | 10 | 0 | 10 |
| Graves' Disease | 10 | 0 | 10 |
| Crohn's Disease | 10 | 0 | 10 |
| Pregnancy multiparous | 10 | 0 | 10 |
| Pregnancy first trimester | 10 | 0 | 10 |
| Pregnancy second trimester | 10 | 0 | 10 |
| Pregnancy third trimester | 10 | 0 | 10 |
| Transplant / Transplant recipient | 10 | 0 | 10 |
| Dialysis patients | 10 | 0 | 10 |
| Hemophiliac / Clotting factor | 10 | 0 | 10 |
| Systemic lupus erythematosus (SLE) | 10 | 0 | 10 |
| Influenza A virus | 10 | 0 | 10 |
| *S. aureus* | 10 | 0 | 10 |
| *P. aeruginosa* | 10 | 0 | 10 |
| *E. coli* | 10 | 0 | 10 |
| **Total** | **290** | **0** | **290** |

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### Seroconversion

30 commercially available patient seroconversion panels were tested using the Access HIV Ag/Ab combo assay and a commercially available HIV Ag/Ab combo comparator assay to determine the seroconversion sensitivity of the assay. The Access HIV Ag/Ab combo assay detected HIV one to two bleeds earlier than the comparator assay in 11 of the 30 panels. Both assays exhibited equivalent detection with no difference in bleed number in 19 of the 30 panels. The results are summarized in the following table.

| Panel ID | HIV Ag/Ab combo first reactive result from initial draw date | | Access HIV Ag/Ab combo Assay vs Comparator assay |
| --- | --- | --- | --- |
| | Access HIV Ag/Ab combo assay (days) | Comparator assay (days) | Difference in bleed number of first reactive result* |
| 0600-0227 | 7 | 7 | 0 |
| 0600-0232 | 18 | 18 | 0 |
| 0600-0237 | 3 | 7 | -1 |
| 0600-0238 | 14 | 17 | -1 |
| 0600-0240 | 47 | 47 | 0 |
| 0600-0244 | 14 | 14 | 0 |
| 0600-0245 | 14 | 17 | -1 |
| 0600-0250 | 26 | 26 | 0 |
| 0600-0251 | 61 | 70 | -2 |
| 0600-0258 | 7 | 9 | -1 |
| 0600-0260 | 14 | 14 | 0 |
| 0600-0261 | 0 | 7 | -2 |
| 0600-0262 | 13 | 13 | 0 |
| 0600-0265 | 28 | 28 | 0 |
| 0600-0271 | 3 | 7 | -1 |
| 0600-0272 | 18 | 18 | 0 |
| HIV6248 | 18 | 18 | 0 |
| HIV9011 | 38 | 38 | 0 |
| HIV9012 | 14 | 16 | -1 |
| HIV9013 | 23 | 25 | -1 |
| HIV9016 | 30 | 30 | 0 |
| HIV9019 | 38 | 38 | 0 |
| HIV9020 | 87 | 90 | -1 |
| HIV9021 | 47 | 47 | 0 |
| HIV9023 | 78 | 78 | 0 |
| HIV9028 | 53 | 53 | 0 |
| HIV9030 | 47 | 47 | 0 |
| HIV9031 | 138 | 146 | -1 |
| HIV9081 | 24 | 24 | 0 |
| HIV9096 | 3 | 3 | 0 |

*The difference in bleed number is compared to the comparator assay. For example, -1 indicates that the comparator assay required 1 additional bleed before reactivity was determined compared to the Access HIV Ag/Ab combo assay.

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### Sensitivity in Antibody Positive non-B Subtype Samples

Sensitivity of the Access HIV Ag/Ab combo assay to detect 33 HIV-1 non-B subtypes (comprising HIV-1 group M subtypes and CRFs, as well as HIV-1 group O) was evaluated. A total of 311 samples were tested and 100% (311/311) were found reactive using the Access HIV Ag/Ab combo assay. The results are summarized in the following table:

| HIV-1 Subtype, CRF, or Group | Number of Specimens | Number Reactive |
| --- | --- | --- |
| A | 5 | 5 |
| A1 | 10 | 10 |
| A2 | 4 | 4 |
| C | 20 | 20 |
| D | 16 | 16 |
| F1 | 12 | 12 |
| F2 | 5 | 5 |
| G | 14 | 14 |
| H | 10 | 10 |
| J | 3 | 3 |
| K | 1 | 1 |
| cpx | 21 | 21 |
| CRF01 | 37 | 37 |
| CRF02 | 75 | 75 |
| CRF03 | 2 | 2 |
| CRF04 | 1 | 1 |
| CRF06 | 9 | 9 |
| CRF07 | 1 | 1 |
| CRF09 | 2 | 2 |
| CRF11 | 11 | 11 |
| CRF12 | 3 | 3 |
| CRF13 | 5 | 5 |
| CRF14 | 1 | 1 |
| CRF18 | 7 | 7 |
| CRF22 | 4 | 4 |
| CRF25 | 3 | 3 |
| CRF37 | 12 | 12 |
| CRF43 | 2 | 2 |
| CRF45 | 2 | 2 |
| CRF49 | 1 | 1 |
| CRF60 | 1 | 1 |
| CRF94 | 1 | 1 |
| HIV-1 group O | 10 | 10 |
| **Total** | **311** | **311** |

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### Sensitivity to Detect Antigen Subtypes

Cell culture supernatants comprising different HIV-1 group M subtypes (A, B, C, D, F, G, H) and CRF-01, 02, 06, 11, 14, 15, 18 and 36 were evaluated with the Access HIV Ag/Ab combo assay. Supernatants from HIV-1 group O (including subtype H and T) and HIV-2 (subtype A and B) were also tested. Of the 50 total supernatants tested, 100% were found to be reactive using the Access HIV Ag/Ab combo assay.

| HIV viral subtype, CRF or group | Number of samples | Number Repeatedly Reactive |
| --- | --- | --- |
| HIV-1 group M - subtype A | 4 | 4 |
| HIV-1 group M - subtype B | 7 | 7 |
| HIV-1 group M - subtype C | 4 | 4 |
| HIV-1 group M - subtype D | 4 | 4 |
| HIV-1 group M - subtype F | 3 | 3 |
| HIV-1 group M - subtype G | 4 | 4 |
| HIV-1 group M - subtype H | 1 | 1 |
| CRF01 | 5 | 5 |
| CRF02 | 4 | 4 |
| CRF06 | 2 | 2 |
| CRF11 | 1 | 1 |
| CRF14 | 1 | 1 |
| CRF15 | 1 | 1 |
| CRF18 | 1 | 1 |
| CRF36 | 1 | 1 |
| HIV-1 group O | 1 | 1 |
| HIV-1 group O - subtype H | 1 | 1 |
| HIV-1 group O - subtype T | 1 | 1 |
| HIV-2 group A | 2 | 2 |
| HIV-2 group B | 2 | 2 |
| **Total** | **50** | **50** |

### Clinical Performance Evaluation

#### Study Overview

A multi-center study was conducted using the DxI 9000 Access Immunoassay Analyzer to evaluate the ability of the Access HIV Ag/Ab combo assay to detect HIV in specimens from the intended use population. This study enrolled adult, pediatric and pregnant subjects, primarily from the U.S., who were considered high risk, low risk, or known positive for HIV infection according to current Centers for Disease Control & Prevention (CDC) recommendations for the diagnosis of HIV infection. The overall study population included 10,254 samples (21.8% Plasma and 78.2% Serum) consisting of 9,079 (88.5%) that were prospectively collected, and an additional 1,175 (11.5%) pre-characterized retrospective samples collected from known positive HIV or high-risk patients.

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### Determination of Patient Infection Status (PIS)

Clinical sensitivity and specificity of the Access HIV Ag/Ab combo assay were evaluated on the DxI 9000 Access Immunoassay Analyzer compared to the final PIS determined following an algorithm aligned with current CDC recommendations for the diagnosis of HIV infection. All samples were tested with the Access HIV Ag/Ab combo assay and an FDA approved HIV Ag/Ab combo comparator assay. Samples found repeatedly reactive on the Access HIV Ag/Ab combo assay, or the comparator HIV Ag/Ab combo assay, were investigated further with confirmatory testing using an FDA approved HIV-1/2 differentiation assay (HIV assay with differentiation between HIV-1 and HIV-2) and/or an FDA approved HIV-1 RNA PCR assay as needed. Subjects with indeterminant final HIV PIS were not included in the analysis.

### Clinical Specificity

A total of 7,156 subjects were tested in the low-risk population, including 6,259 low-risk adults, 408 low-risk pediatrics and 489 low-risk pregnant women. A total of 1,514 subjects were tested in the high-risk population, including 570 high-risk adults, 106 high-risk pediatrics, 146 high-risk pregnant women and 692 from HIV-2 endemic regions. The overall summary of the comparison of the Access HIV Ag/Ab combo assay and the comparator HIV Ag/Ab combo assay is shown in the following table.

### Reactivity of Access HIV Ag/Ab Combo Assay Compared to the Comparator HIV Ag/Ab Combo Assay

| Category | N Tested | Access HIV Ag/Ab combo assay | | | FDA approved HIV Ag/Ab combo comparator assay | | | Final HIV PIS | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | NR | IR | RR | NR | IR | RR | Positive | Negative | |
| HIV Low Risk | Adults (non-pregnant) | 6,259 | 6,060 | 201 | 199 | 6,007 | 280 | 252 | 174 | 6,085 |
| | Pediatrics (non-pregnant) | 408 | 407 | 1 | 1 | 404 | 6 | 4 | 1 | 407 |
| | Pregnant | 489 | 489 | 0 | 0 | 483 | 6 | 6 | 0 | 489 |
| HIV High Risk | Adults (non-pregnant) | 570 | 548 | 22 | 22 | 541 | 32 | 29 | 21 | 549 |
| | Pediatrics (non-pregnant) | 106 | 104 | 2 | 2 | 102 | 4 | 4 | 2 | 104 |
| | Pregnant | 146 | 146 | 0 | 0 | 145 | 3 | 1 | 0 | 146 |
| HIV High Risk from HIV-2 endemic regions | | 692 | 685 | 7 | 7 | 686 | 6 | 6 | 5 | 687 |
| **Total** | | **8,670** | **8,439** | **233** | **231*** | **8,368** | **337** | **302*** | **203*** | **8,467** |

NR = nonreactive, IR = initially reactive, RR = repeatedly reactive, PIS = Patient Infection Status

*Both the Access HIV Ag/Ab combo assay and the comparator HIV Ag/Ab combo assay had samples that were repeat reactive but had a final negative HIV PIS.

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## Summary of Clinical Specificity Results

| Cohort | Matrix | Clinical Specificity of the Access HIV Ag/Ab combo assay | |
| --- | --- | --- | --- |
| | | % (n/N) | 95% CI |
| HIV Low Risk | All samples | 99.6 (6,956/6,981) | 99.5-99.8 |
| | Serum | 99.7 (5,184/5,197) | 99.6-99.9 |
| | Plasma | 99.3 (1,772/1,784) | 98.8-99.6 |
| HIV High Risk* | All samples | 99.8 (1,483/1,486) | 99.4-99.9 |
| | Serum | 99.8 (1,482/1,485) | 99.4-99.9 |
| | Plasma | 100.0 (1/1) | 20.7-100.0 |
| **Total** | **All samples** | **99.7% (8,439/8,467)** | **99.5 - 99.8** |

*Includes high-risk from HIV-2 endemic regions

### Low Risk Cohort

A total of 7,156 samples from individuals at low risk for HIV were tested, of which 175 had a final HIV PIS of 'positive' and 6,981 had a final HIV PIS of 'negative'. Based on the data, 6,956/6,981 were nonreactive on the Access HIV Ag/Ab combo assay. Of the 25 subjects that were reactive on the Access HIV Ag/Ab combo assay and also had a final HIV PIS status of negative, 4 were also reactive on the comparator HIV Ag/Ab combo assay. Additionally, 1 subject that was also reactive on the comparator assay was HIV indeterminant on the HIV-1/2 differentiation assay.

### High Risk Cohort

A total of 1,514 samples from individuals at high risk for HIV were tested, of which 28 had a final HIV PIS of 'positive' and 1,486 had a final HIV PIS of 'negative'. Based on the data, 1,483/1,486 were nonreactive on the Access HIV Ag/Ab combo assay. Of the 3 subjects that were reactive on the Access HIV Ag/Ab combo assay and also had a final HIV PIS status of negative, 2 were also reactive on the comparator HIV Ag/Ab combo assay. Additionally, 1 subject that was also reactive on the comparator assay was HIV indeterminant on the HIV-1/2 differentiation assay.

The overall specificity of the Access HIV Ag/Ab combo assay, for both low and high risk populations, was found to be 99.7% (8,439/8,467) with a 95th percentile confidence interval of 99.5% to 99.8%.

### Clinical Sensitivity

#### Reactivity in Individuals Known to Be Positive for HIV

The clinical sensitivity of the Access HIV Ag/Ab combo assay in individuals known to be positive for HIV was determined using a total of 1,584 subjects and included 1,153 HIV-1 known positive adult subjects, 56 HIV-1 confirmed positive pediatric subjects, 48 HIV-1 confirmed positive pregnant subjects, 178 known HIV-2 positive subjects, 37 known HIV-1 group O positive samples, 80 HIV-1 group M positive samples and 32 HIV-1 p24 antigen known positive samples. An overall summary of the comparison of the Access HIV Ag/Ab combo assay compared to the FDA approved HIV Ag/Ab combo assay for all samples based on each subject cohort is shown in the following table.

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### Reactivity in Individuals Known to Be Positive for HIV

| Category | N Tested | Access HIV Ag/Ab combo assay | | | FDA approved HIV Ag/Ab combo comparator assay | | | Final HIV PIS Positive | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | NR | IR | RR | NR | IR | RR | | |
| Known HIV-1 Positive | Adult (non-Pregnant) | 1,153 | 0 | 1,153 | 1,153 | 0 | 1,153 | 1,153 | 1,153 |
| | Pediatric (non-Pregnant) | 56 | 0 | 56 | 56 | 0 | 56 | 56 | 56 |
| | Pregnant | 48 | 0 | 48 | 48 | 0 | 48 | 48 | 48 |
| Known HIV-2 Positive | All Subjects | 178 | 0 | 178 | 178 | 0 | 178 | 178 | 178 |
| Known HIV -1 group O positive | All Subjects | 37 | 0 | 37 | 37 | 0 | 37 | 37 | 37 |
| Known HIV-1 group M positive | All Subjects | 80 | 0 | 80 | 80 | 0 | 80 | 80 | 80 |
| Known HIV-1 p24 antigen positive | All Subjects | 32* | 0 | 32 | 32 | 3 | 28 | 28 | 32 |
| **Total** | | **1,584** | **0** | **1,584** | **1,584** | **3** | **1,580** | **1,580** | **1,584** |

NR = nonreactive, IR = initially reactive, RR = repeatedly reactive, PIS = Patient Infection Status

*The total N tested for known HIV-1 p24 antigen positive samples was 32 for the Access HIV Ag/Ab combo assay and 31 for the FDA approved comparator HIV Ag/Ab combo assay.

### Comparison of the Clinical Sensitivity of the Access HIV Ag/Ab Combo Assay with an FDA Approved HIV Ag/Ab Combo Comparator Assay

The sensitivity of the Access HIV Ag/Ab combo assay in individuals known to be positive for HIV was determined using 1,584 samples. All samples (1,584/1,584) had a final HIV PIS status of 'positive' resulting in a clinical sensitivity of 100% with a 95th percentile confidence interval of 99.8% to 100%.

| Cohort | Access HIV Ag/Ab combo assay | | FDA approved HIV Ag/Ab combo comparator assay | | |
| --- | --- | --- | --- | --- | --- |
| | | Clinical Sensitivity % (n/N) | 95% CI | Clinical Sensitivity % (n/N) | 95% CI |
| Known HIV-1 Positive | Adult (non-pregnant) | 100.0 (1,153/1,153) | 99.7-100.0 | 100.0 (1,153/1,153) | 99.7-100.0 |
| | Pediatric (non-Pregnant) | 100.0 (56/56) | 93.6-100.0 | 100.0 (56/56) | 93.6-100.0 |
| | Pregnant | 100.0 (48/48) | 92.6-100.0 | 100.0 (48/48) | 92.6-100.0 |
| Known HIV-2 Positive | All Subjects | 100.0 (178/178) | 97.9-100.0 | 100.0 (178/178) | 97.9-100.0 |
| Known HIV -1 group O positive | All Subjects | 100.0 (37/37) | 90.6-100.0 | 100.0 (37/37) | 90.6-100.0 |
| Known HIV-1 group M positive | All Subjects | 100.0 (80/80) | 95.4-100.0 | 100.0 (80/80) | 95.4-100.0 |
| Known HIV-1 p24 antigen positive | All Subjects | 100.0 (32/32)* | 89.3-100.0 | 90.3 (28/31)* | 75.1-96.7 |
| **Total** | | **100.0 (1,584/1,584)** | **99.8-100.0** | **99.8 (1,580/1,583)** | **99.4-99.9** |

*The total N tested for known HIV-1 p24 antigen positive samples was 32 for the Access HIV Ag/Ab combo assay (all confirmed PIS positive) and 31 for the FDA approved HIV Ag/Ab combo comparator assay (all confirmed PIS positive).

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### Sensitivity of All Subjects Positive for HIV

The overall clinical sensitivity of the Access HIV Ag/Ab combo assay on the DxI 9000 Access Immunoassay Analyzer was determined in 1,584 samples known to be positive for HIV-1 or HIV-2, plus 203 samples that were found to be positive from the low-risk and high-risk populations. All 1,787 samples had a final HIV PIS of 'positive' for analysis.

| Cohort | Matrix | Sensitivity | |
| --- | --- | --- | --- |
| | | % (n/N) | 95% CI |
| Subjects known positive for HIV | All samples | 100.0 (1,584/1,584) | 99.8-100.0 |
| | Serum | 100.0 (1,228/1,228) | 99.7-100.0 |
| | Plasma | 100.0 (356/356) | 98.9-100.0 |
| All HIV positive samples | All samples | 100.0 (1,787/1,787) | 99.8-100.0 |
| | Serum | 100.0 (1,325/1,325) | 99.7-100.0 |
| | Plasma | 100.0 (462/462) | 99.2-100.0 |

The overall sensitivity of the Access HIV Ag/Ab combo assay was found to be 100.0% (1,787/1,787) with a 95th percentile confidence interval of 99.8% to 100.0%.

### Reactivity in Individuals at High-Risk of HIV-1/2 Infection

The sensitivity of the Access HIV Ag/Ab combo in individuals at high risk for HIV was determined using a total of 1,514 subjects, including 570 adults, 106 pediatric subjects and 146 pregnant subjects, as well as an additional 692 subjects (524 adult and 168 pediatric) from an HIV-2 endemic area.

| Category | N Tested | Access HIV Ag/Ab combo assay | | | FDA approved Ag/Ab combo comparator assay | | | Final HIV PIS Positive | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | NR | IR | RR | NR | IR | RR | | |
| High Risk n = 822 | Adults (non-Pregnant) | 570 | 548 | 22 | 22 | 541 | 32 | 29 | 21 |
| | Pediatrics (non-Pregnant) | 106 | 104 | 2 | 2 | 102 | 4 | 4 | 2 |
| | Pregnant | 146 | 146 | 0 | 0 | 145 | 3 | 1 | 0 |
| High-risk HIV-2 from endemic regions n = 692 | Adults (non-Pregnant) | 524 | 517 | 7 | 7 | 518 | 6 | 6 | 5 |
| | Pediatrics (non-Pregnant) | 168 | 168 | 0 | 0 | 168 | 0 | 0 | 0 |
| **Total** | | **1,514** | **1,483** | **31** | **31** | **1,474** | **45** | **40** | **28** |

NR = nonreactive, IR = initially reactive, RR = repeatedly reactive, PIS = Patient Infection Status

Of the total 1,514 subjects included in the sensitivity analysis, 28 subjects had a final HIV PIS of 'positive'. Five (5) of the 28 were collected from an HIV-2 endemic region. The final sensitivity of the Access HIV Ag/Ab combo assay for patients at high risk for HIV was 100% (28/28) with a 95th percentile confidence interval of 87.9% to 100%.

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### Reactivity in Pregnant Women

The clinical sensitivity of the Access HIV Ag/Ab combo assay in samples collected from pregnant women was determined using a total of 635 subjects and included 489 at low risk for HIV and 146 at high risk for HIV. A summary of the results of the Access HIV Ag/Ab combo assay and an FDA approved HIV Ag/Ab combo comparator assay for samples from pregnant women at low risk and high risk for HIV is shown in the following tables.

#### Low Risk Pregnant Cohort

| Low-Risk Pregnant Women by Trimester | N Tested | Access HIV Ag/Ab combo assay | | | FDA approved HIV Ag/Ab combo comparator assay | | | Final HIV PIS positive |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | NR | IR | RR | NR | IR | RR | |
| First | 162 | 162 | 0 | 0 | 160 | 2 | 2 | 0 |
| Second | 168 | 168 | 0 | 0 | 166 | 2 | 2 | 0 |
| Third | 159 | 159 | 0 | 0 | 157 | 2 | 2 | 0 |
| **Total** | **489** | **489** | **0** | **0** | **483** | **6** | **6** | **0** |

NR = nonreactive, IR = initially reactive, RR = repeatedly reactive, PIS = Patient Infection Status

#### High Risk Pregnant Cohort

| High-Risk Pregnant Women by Trimester | N Tested | Access HIV Ag/Ab combo assay | | | FDA approved HIV Ag/Ab combo comparator assay | | | Final HIV PIS positive |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | NR | IR | RR | NR | IR | RR | |
| First | 57 | 57 | 0 | 0 | 56 | 2 | 1 | 0 |
| Second | 43 | 43 | 0 | 0 | 43 | 0 | 0 | 0 |
| Third | 46 | 46 | 0 | 0 | 46 | 1 | 0 | 0 |
| **Total** | **146** | **146** | **0** | **0** | **145** | **3** | **1** | **0** |

NR = nonreactive, IR = initially reactive, RR = repeatedly reactive, PIS = Patient Infection Status

### Reactivity in the Pediatric Population

The clinical sensitivity of the Access HIV Ag/Ab combo assay in pediatric individuals was determined using a total of 682 subjects and included 408 at low risk for HIV and 274 at high risk for HIV. A summary of the results of the Access HIV Ag/Ab combo assay and the comparator HIV Ag/Ab combo assay for low-risk and high-risk pediatric specimens is shown in the following tables.

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### Low Risk Pediatric Cohort

The clinical sensitivity of the Access HIV Ag/Ab combo assay in the low-risk pediatric population was found to be 100.0% (1/1) with a 95th percentile confidence interval of 20.7% to 100.0%.

| Low-risk Pediatrics (years) | N Tested | Access HIV Ag/Ab combo assay | | | FDA approved HIV Ag/Ab combo comparator assay | | | Final HIV PIS positive |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | NR | IR | RR | NR | IR | RR | |
| 2-5 | 9 | 9 | 0 | 0 | 9 | 0 | 0 | 0 |
| 6-10 | 26 | 26 | 0 | 0 | 26 | 0 | 0 | 0 |
| 11-15 | 67 | 67 | 0 | 0 | 66 | 1 | 1 | 0 |
| 16-21 | 306 | 305 | 1 | 1 | 303 | 5 | 3 | 1 |

NR = nonreactive, IR = initially reactive, RR = repeatedly reactive, PIS = Patient Infection Status

### High Risk Pediatric Cohort

The clinical sensitivity of the Access HIV Ag/Ab combo assay in the high-risk pediatric population was found to be 100.0% (2/2) with a 95th percentile confidence interval of 34.2% to 100.0%.

| High-risk Pediatrics by Age (years)* | N Tested | Access HIV Ag/Ab combo assay | | | FDA approved HIV Ag/Ab combo comparator assay | | | Final HIV PIS positive |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | NR | IR | RR | NR | IR | RR | |
| 11-15 | 7 | 7 | 0 | 0 | 7 | 0 | 0 | 0 |
| 16-21 | 267 | 265 | 2 | 2 | 263 | 4 | 4 | 2 |

NR = nonreactive, IR = initially reactive, RR = repeatedly reactive, PIS = Patient Infection Status

*All results for high-risk pediatric subjects were for age groups greater than or equal to eleven years of age.

### Substantial Equivalence Comparison Conclusion

The results of non-clinical analytical and clinical performance studies demonstrate that the Beckman Coulter Access HIV Ag/Ab combo assay for use on the DxI 9000 Access Immunoassay Analyzer is as safe, as effective, and performs as well as the predicate device.

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