← Product Code [MZF](/productcode/MZF) · BK261345

# HIV Combo Next Assay (BK261345)

_Abbott Laboratories Abbott Park, IL 60064 · MZF · Jun 29, 2026 · Microbiology · SESE_

**Canonical URL:** https://fda.innolitics.com/device/BK261345

## Device Facts

- **Applicant:** Abbott Laboratories Abbott Park, IL 60064
- **Product Code:** [MZF](/productcode/MZF.md)
- **Decision Date:** Jun 29, 2026
- **Decision:** SESE
- **Regulation:** 21 CFR 866.3956
- **Device Class:** Class 2
- **Review Panel:** Microbiology
- **Attributes:** Pediatric

## Indications for Use

The HIV Combo Next assay is a chemiluminescent microparticle immunoassay (CMIA) used for the simultaneous qualitative detection of human immunodeficiency virus type 1 (HIV-1) p24 antigen and antibodies to HIV-1 group M and O and/or type 2 (HIV-2) in human serum and plasma (EDTA and heparin) on the Alinity i system. The HIV Combo Next assay is 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 (greater than or equal to two years of age) and in pregnant women. An HIV Combo Next reactive result does not distinguish between the detection of HIV-1 antigen, HIV-2 antigen, HIV-1 antibodies and HIV-2 antibodies. This assay is not intended to be used for monitoring patient status, or for screening donors of blood, plasma, or human cells, tissues, and cellular and tissue-based products (HCT/Ps) for HIV. 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.

## Device Story

Automated chemiluminescent microparticle immunoassay (CMIA) for Alinity i system; detects HIV-1 p24 antigen and HIV-1/HIV-2 antibodies in serum/plasma. Process: sample, paramagnetic microparticles (coated with HIV-1/HIV-2 antigens and anti-HIV p24 antibody), and acridinium-labeled conjugates form reaction mixture; incubation; wash cycles; addition of Pre-Trigger/Trigger solutions. System measures chemiluminescent relative light units (RLU); compares RLU to active calibration cutoff. Used in clinical laboratories; operated by trained personnel. Output: qualitative reactive/nonreactive result. Aids diagnosis of HIV-1/HIV-2 infection, including acute/primary infection. Reactive results require supplemental testing.

## Clinical Evidence

Multicenter study of 10,063 serum/plasma samples. Sensitivity: 100% (2137/2137; 95% CI: 99.83–100%) across HIV-1/HIV-2 antibody and antigen positive cohorts. Specificity: 99.67% (7865/7891; 95% CI: 99.52–99.78%) in low-risk and increased-risk populations. Reproducibility confirmed across sites, lots, and days.

## Technological Characteristics

CMIA technology; paramagnetic microparticles coated with HIV-1/HIV-2 antigens and anti-HIV p24 monoclonal antibodies. Reagents include acridinium-labeled conjugates, assay diluent, and sodium azide preservative. Automated system (Alinity i); chemiluminescent detection; qualitative output. Calibrator traceable to WHO International Standard (NIBSC 90/636).

## Regulatory 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

- ARCHITECT HIV Ag/Ab Combo (BP090080)

## Submission Summary (Full Text)

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# 510(k) Summary

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

|  **510(k) Owner's Name** | Abbott Laboratories  |
| --- | --- |
|  **Company Address** | Department C2D2 100 Abbott Park Road Abbott Park, IL 60064  |
|  **Phone Number** | (224) 668-3735  |

## Device

|  **Proprietary Name** | HIV Combo Next Reagent Kit HIV Combo Next Calibrator HIV Combo Next Controls  |
| --- | --- |
|  **Common Name** | HIV Combo Next or HIV Combo Nx  |
|  **Classification Name** | Human immunodeficiency virus (HIV) serological diagnostic and/or supplemental test  |
|  **Regulation Number** | 21 CFR 866.3956  |
|  **Product Code** | MZF  |

## Predicate Device

|  **Predicate Trade Name** | ARCHITECT HIV Ag/Ab Combo  |
| --- | --- |
|  **Common Name** | ARCHITECT HIV Ag/Ab Combo  |
|  **Classification Name** | Human immunodeficiency virus (HIV) serological diagnostic and/or supplemental test  |
|  **Regulation Number** | 21 CFR 866.3956  |
|  **Product Code** | MZF  |
|  **Predicate STN Number** | BP090080  |

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# I. Description of Device

# Reagents

The kit configuration of the HIV Combo Next Reagent Kit is described below (Table 1).

Table 1. Components of the HIV Combo Next Reagent Kit

|  List Number (LN) | 06Q8621 | 06Q8631  |
| --- | --- | --- |
|  Tests per cartridge | 100 | 600  |
|  Number of cartridge sets per kit | 2 | 2  |
|  Tests per kit | 200 | 1200  |
|  Microparticles | 6.6 mL | 32.1 mL  |
|  Conjugate 1 | 6.1 mL | 31.6 mL  |
|  Assay Diluent | 6.3 mL | 31.8 mL  |
|  Conjugate 2 | 6.1 mL | 31.6 mL  |

- Microparticles: HIV-1/HIV-2 antigen (recombinant) and HIV p24 antibody (mouse, monoclonal) coated microparticles in TRIS buffered saline. Minimum concentration: \(0.06\%\) solids. Preservative: sodium azide.
- Conjugate 1: Acridinium-labeled HIV p24 antibody (recombinant) and acridinium-labeled HIV-1 antigen (recombinant) conjugate in phosphate buffer with protein stabilizers (bovine) and surfactant. Minimum concentration: \(0.04\mu \mathrm{g / mL}\). Preservative: sodium azide.
- Assay Diluent: Phosphate buffer with detergent. Preservative: sodium azide.
- Conjugate 2: Acridinium-labeled HIV-1/HIV-2 antigens (recombinant), acridinium-labeled HIV-1/HIV-2 synthetic peptides conjugate in phosphate buffer with protein stabilizers (bovine) and surfactant. Minimum concentration: \(0.35\mu \mathrm{g / mL}\). Preservative: sodium azide.

# Calibrator

The HIV Combo Next Calibrator is described below.

- Calibrator 1: Contains purified HIV-1 viral lysate prepared in TRIS buffered saline with protein (bovine serum albumin) additive. Preservative: sodium azide.

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**Table 2. Details of the HIV Combo Next Calibrator**

|  Calibrator | Quantity | Color  |
| --- | --- | --- |
|  Calibrator 1 | 1 x 3.0 mL | Red^{a}  |

$^{a}$ Dye: Red D&C No. 33

The HIV Combo Next Calibrator is traceable to the World Health Organization (WHO) International Standard HIV-1 P24 Antigen NIBSC code: 90/636.

# Controls

The HIV Combo Next Controls are described below.

- Negative Control: Contains recalcified human plasma. Preservatives: sodium azide and antimicrobial agent.
- Positive Control 1: contains recalcified human plasma and is reactive for anti-HIV-1 (inactivated). Preservatives: sodium azide and antimicrobial agent.
- Positive Control 2: contains recalcified human plasma and is reactive for anti-HIV-2 (inactivated). Preservatives: sodium azide and antimicrobial agents.
- Positive Control 3: contains purified HIV viral lysate prepared in TRIS buffered saline with protein (bovine) stabilizer. Preservative: sodium azide.
- Positive Control 4: contains purified HIV-1 group O monoclonal antibody prepared in recalcified negative human plasma. Preservative: sodium azide.

The ranges for the controls are provided in Table 3 below. The ranges may be used for individual replicate control specifications on the Alinity i system.

**Table 3. Components of the HIV Combo Next Controls**

|  Control | Quantity | Color | Range S/CO  |
| --- | --- | --- | --- |
|  Negative Control | 2 x 3.0 mL | Natural | 0.00 – 0.50  |
|  Positive Control 1 | 2 x 3.0 mL | Blue^{a} | 1.30 – 7.05  |
|  Positive Control 2 | 2 x 3.0 mL | Yellow^{b} | 1.10 – 4.40  |
|  Positive Control 3 | 2 x 3.0 mL | Purple^{c} | 1.13 – 2.77  |
|  Positive Control 4 | 2 x 3.0 mL | Orange^{d} | 1.18 – 4.00  |

$^{a}$ Dye: Acid Blue No. 9

$^{b}$ Dye: Acid Yellow No. 23

$^{c}$ Dye: Acid Blue No. 9 and Red D&C No. 33

$^{d}$ Dye: Acid Yellow No. 23 and Red D&C No. 33

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The HIV Combo Next Controls are traceable to internal reference standards.

## Biological Principles of the Procedure

This assay is an automated combination of a one-step immunoassay for the qualitative detection of HIV-1 p24 antigen and antibodies to HIV-1 (group M) and a two-step immunoassay for the qualitative detection of antibodies to HIV-1 (group M and group O), and antibodies to HIV-2 in human serum and plasma (EDTA and heparin) using chemiluminescent microparticle immunoassay (CMIA) technology.

Sample, anti-HIV p24 and HIV antigen coated paramagnetic microparticles, assay diluent, and anti-HIV p24 and HIV antigen acridinium-labeled conjugates are combined to create a reaction mixture and incubated. The HIV antigen present in the sample binds to the anti-HIV p24 coated microparticles and to the anti-HIV p24 acridinium-labeled conjugate. The anti-HIV antibodies present in the sample bind to the HIV antigen coated microparticles and to the HIV antigen acridinium-labeled conjugate. After washing, additional HIV antigen acridinium-labeled conjugate is added. HIV antibodies captured in the first step bind additional HIV antigen acridinium-labeled conjugate in the second step. Following another wash cycle, Pre-Trigger and Trigger Solutions are added.

The resulting chemiluminescent reaction is measured as a relative light unit (RLU). There is a direct relationship between the amount of HIV antigen and/or antibodies to HIV in the sample and the RLU detected by the system optics.

The presence or absence of HIV antigen and/or antibodies to HIV in the sample is determined by comparing the chemiluminescent RLU in the reaction to the cutoff RLU determined from an active calibration.

## II. Intended Use of the Device

The HIV Combo Next assay is a chemiluminescent microparticle immunoassay (CMIA) used for the simultaneous qualitative detection of human immunodeficiency virus type 1 (HIV-1) p24 antigen and antibodies to HIV-1 group M and O and/or type 2 (HIV-2) in human serum and plasma (EDTA and heparin) on the Alinity i system.

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The HIV Combo Next assay is 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 (greater than or equal to two years of age) and in pregnant women.

An HIV Combo Next reactive result does not distinguish between the detection of HIV-1 antigen, HIV-2 antigen, HIV-1 antibodies and HIV-2 antibodies.

This assay is not intended to be used for monitoring patient status, or for screening donors of blood, plasma, or human cells, tissues, and cellular and tissue-based products (HCT/Ps) for HIV. 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.

### III. Comparison of Technological Characteristics

The HIV Combo Next assay (subject device) utilizes a CMIA methodology for the simultaneous qualitative detection of human immunodeficiency virus type 1 (HIV-1) p24 antigen and antibodies to HIV-1 group M and O and/or type 2 (HIV-2) in human serum and plasma (EDTA and heparin) on the Alinity i system.

The similarities and differences between the subject and the predicate devices are presented in Tables 4 and 5.

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Table 4. Similarities Between the Subject and the Predicate Devices

|  Characteristics | Subject Device HIV Combo Next for Alinity i BK261345 | Predicate Device ARCHITECT HIV Ag/Ab Combo BP090080  |
| --- | --- | --- |
|  Methodology | Chemiluminescent microparticle immunoassay (CMIA) | Same  |
|  Intended Use and Indications for Use | The HIV Combo Next assay is a chemiluminescent microparticle immunoassay (CMIA) used for the simultaneous qualitative detection of human immunodeficiency virus type 1 (HIV-1) p24 antigen and antibodies to HIV-1 group M and O and/or type 2 (HIV-2) in human serum and plasma (EDTA and heparin) on the Alinity i system. The HIV Combo Next assay is 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 (greater than or equal to two years of age) and in pregnant women. An HIV Combo Next reactive result does not distinguish between the detection of HIV-1 antigen, HIV-2 antigen, HIV-1 antibodies and HIV-2 antibodies. This assay is not intended to be used for monitoring patient status, or for screening donors of blood, plasma, or human cells, tissues, and cellular and tissue-based products (HCT/Ps) for HIV. 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. | 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.  |

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|  Characteristics | Subject Device HIV Combo Next for Alinity i BK261345 | Predicate Device ARCHITECT HIV Ag/Ab Combo BP090080  |
| --- | --- | --- |
|  Type of Specimen | Serum and Plasma | Same  |
|  Interpretation of Results | Initial Result ≥ 1.00 S/CO Reactive. Retest in duplicate. < 1.00 S/CO Nonreactive. No retest required. Final Interpretation • If initial result is nonreactive, then no retest is required, and the final interpretation is nonreactive. HIV-1 p24 Ag and HIV-1/HIV-2 Ab not detected. • If initial result is reactive, and both retest results are < 1.00 S/CO, the final interpretation is nonreactive. HIV-1 p24 Ag and HIV-1/HIV-2 Ab not detected. • If initial result is reactive, and if one or both retest results are ≥ 1.00 S/CO, the final interpretation is reactive. Presumptive evidence of HIV-1 p24 Ag and/or HIV-1/HIV-2 Ab; perform supplemental assay. A specimen with a reactive result should be investigated further following current guidelines. | Same  |
|  Cut Off | 1.00 S/CO | Same  |
|  Calibrator(s) | 1 Calibrator | Same  |
|  Control(s) | 5 Controls (1 Negative, 4 Positive) | Same  |

Abbreviations: S/CO = signal of sample / signal of cutoff.

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Table 5. Differences Between the Subject and the Predicate Devices

|  Characteristics | Subject Device HIV Combo Next for Alinity i BK261345 | Predicate Device ARCHITECT HIV Ag/Ab Combo BP090080  |
| --- | --- | --- |
|  Assay Type | Qualitative, combination 1-step/2-step | Qualitative 2-step  |
|  Components | 4 reagent components: Microparticles: HIV-1/HIV-2 antigen (recombinant) and HIV p24 antibody (mouse, monoclonal) coated microparticles Conjugate 1: acridinium-labeled HIV p24 antibody (recombinant) and acridinium-labeled HIV-1 antigen (recombinant) conjugate Assay Diluent: phosphate buffer with detergent Conjugate 2: acridinium-labeled HIV-1/HIV-2 antigens (recombinant), acridinium-labeled HIV-1/HIV-2 synthetic peptides conjugate | 3 reagent components: Microparticles: HIV-1/HIV-2 antigen and HIV p24 antibody (mouse IgG, monoclonal) coated microparticles Conjugate: Acridinium-labeled HIV-1 antigens, acridinium-labeled HIV-1/HIV-2 synthetic peptides, and acridinium-labeled HIV p24 antibody (mouse IgG, monoclonal) conjugates Assay Diluent: TRIS buffer with protein (mouse serum and IgG) additive and surfactant  |

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## IV. Summary of Nonclinical Performance

### A. Within-Laboratory Precision (20-Day)

This study was performed based on guidance from CLSI EP05-A3\*. Testing was conducted using 3 lots of the HIV Combo Next reagents, 3 lots of the HIV Combo Next Calibrator, 1 lot of the HIV Combo Next Controls, and 2 instruments. Five controls and 7 recalcified human plasma panels were tested in 2 replicates, twice per day over 20 days on 3 reagent lot/calibrator lot combinations on 2 instruments, where a unique reagent lot and a unique calibrator lot are paired. The results support the conclusion that the HIV Combo Next assay is reproducible for within run, between run, between days, and within laboratory. The performance is shown in Table 6.

**Table 6. Precision Results for HIV Combo Next**

|  Sample | n | Mean (S/CO) | Repeatability (Within-Run) |   | Between-Run |   | Between-Day |   | Within-Laboratory^{a}  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  SD | %CV | SD | %CV | SD | %CV | SD | %CV  |
|  Negative Control | 480 | 0.09 | 0.006 | 7.5 | 0.000 | 0.0 | 0.003 | 3.4 | 0.007 | 8.2  |
|  Positive Control 1 | 480 | 3.07 | 0.097 | 3.2 | 0.000 | 0.0 | 0.084 | 2.7 | 0.128 | 4.2  |
|  Positive Control 2 | 480 | 2.10 | 0.057 | 2.7 | 0.024 | 1.2 | 0.063 | 3.0 | 0.089 | 4.2  |
|  Positive Control 3 | 480 | 1.96 | 0.047 | 2.4 | 0.029 | 1.5 | 0.037 | 1.9 | 0.066 | 3.4  |
|  Positive Control 4 | 480 | 2.25 | 0.074 | 3.3 | 0.000 | 0.0 | 0.061 | 2.7 | 0.096 | 4.3  |
|  HIV-1 Ab Low-Positive Panel | 480 | 1.24 | 0.035 | 2.8 | 0.018 | 1.4 | 0.020 | 1.6 | 0.044 | 3.5  |
|  HIV-2 Ab Low-Positive Panel | 480 | 1.18 | 0.038 | 3.2 | 0.004 | 0.4 | 0.030 | 2.6 | 0.049 | 4.1  |
|  HIV-1 gO Ab Low-Positive Panel | 480 | 1.18 | 0.035 | 2.9 | 0.012 | 1.0 | 0.032 | 2.7 | 0.049 | 4.1  |
|  HIV-1 p24 Ag Low-Positive Panel | 480 | 1.26 | 0.031 | 2.5 | 0.013 | 1.1 | 0.026 | 2.0 | 0.043 | 3.4  |
|  HIV-1 p24 Ag High Negative Panel | 480 | 0.81 | 0.024 | 3.0 | 0.008 | 1.0 | 0.018 | 2.2 | 0.031 | 3.8  |
|  HIV-1 Ab High Negative Panel | 480 | 0.85 | 0.028 | 3.2 | 0.014 | 1.6 | 0.034 | 4.0 | 0.046 | 5.4  |
|  HIV-1 p24 Ag Moderate Positive Panel | 480 | 2.56 | 0.062 | 2.4 | 0.018 | 0.7 | 0.053 | 2.1 | 0.083 | 3.3  |

SD: Standard Deviation; %CV: Coefficient of Variation

$^{a}$ Includes repeatability (within-run), between-run, and between-day variability.

\* Clinical and Laboratory Standards Institute (CLSI). *Evaluation of Precision of Quantitative Measurement Procedures: Approved Guideline–Third Edition*. CLSI Document EP05-A3. Wayne, PA: CLSI; 2014.

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## B. Lower Limits of Measurement

A study was performed based on guidance from CLSI EP17-A2\*. Testing was conducted using 3 lots of the HIV Combo Next reagents on 1 instrument over a minimum of 3 days. The maximum observed limit of blank (LoB) and limit of detection (LoD) are summarized below.

|   | HIV Antibody (S/CO) | HIV-1 p24 Antigen (S/CO)  |
| --- | --- | --- |
|  LoB^{a} | 0.08 | 0.08  |
|  LoD^{b} | 0.13 | 0.15  |

$^{a}$The LoB represents the 95th percentile from n ≥ 60 replicates of zero-analyte samples.

$^{b}$The LoD represents the lowest concentration at which the analyte can be detected with 95% probability based on n ≥ 60 replicates of low-analyte level samples.

## C. Antibody Sensitivity

A total of 631 specimens identified as anti-HIV-1 group M, group O, group N, group P, and anti-HIV-2 were evaluated using the HIV Combo Next assay on the Alinity i. The anti-HIV-1 group M subtypes and anti-HIV-1 group N and P specimens were from Cameroon, Republic of the Congo, Thailand, Brazil, South Africa, Germany, Ghana, Senegal, Argentina, Equatorial Guinea, Mexico, Spain, Saudi Arabia, U.S., and Kinshasa. The anti-HIV-1 group O specimens were from Cameroon, Equatorial Guinea, Spain, and the U.S. The anti-HIV-2 specimens were from Côte d’Ivoire, Guinea-Bissau, and Cameroon. The HIV-1/HIV-2 antibody sensitivity is summarized below (Table 7). The HIV Combo Next assay detected all 631 antibody-positive specimens, yielding 100% sensitivity across all tested HIV groups and subtypes.

**Table 7. Antibody Sensitivity of HIV Combo Next**

|  Category | Subtype | Count | Number Reactive  |
| --- | --- | --- | --- |
|  HIV-1 group M |  | 211 | 211  |
|   |  A | 40 | 40  |
|   |  A1 | 4 | 4  |
|   |  AE | 3 | 3  |

\* Clinical and Laboratory Standards Institute (CLSI). *Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline–Second Edition*. CLSI Guideline EP17-A2. Wayne, PA: CLSI; 2012.

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|  Category | Subtype | Count | Number Reactive  |
| --- | --- | --- | --- |
|   | AG | 3 | 3  |
|   |  B | 46 | 46  |
|   |  C | 37 | 37  |
|   |  D | 21 | 21  |
|   |  F | 22 | 22  |
|   |  F2 | 3 | 3  |
|   |  G | 17 | 17  |
|   |  H | 9 | 9  |
|   |  J | 3 | 3  |
|   |  K | 2 | 2  |
|   |  L | 1 | 1  |
|  **HIV-1 group M circulating recombinant form (CRF)** |  | **141** | **141**  |
|   |  CRF18_complex | 3 | 3  |
|   |  CRF37_complex | 3 | 3  |
|   |  CRF02_subtype A and G | 3 | 3  |
|   |  CRF01 | 31 | 31  |
|   |  CRF02 | 34 | 34  |
|   |  CRF03 | 3 | 3  |
|   |  CRF06 | 7 | 7  |
|   |  CRF09 | 4 | 4  |
|   |  CRF11 | 10 | 10  |
|   |  CRF13 | 11 | 11  |
|   |  CRF14 | 2 | 2  |
|   |  CRF18 | 3 | 3  |
|   |  CRF22 | 8 | 8  |
|   |  CRF25 | 4 | 4  |
|   |  CRF26 | 1 | 1  |
|   |  CRF36 | 2 | 2  |
|   |  CRF37 | 8 | 8  |
|   |  CRF43 | 3 | 3  |
|   |  CRF45 | 1 | 1  |
|  **HIV-1 group M unique recombinant form (URF)** |  | **99** | **99**  |
|  **HIV-1 group O** |  | **55** | **55**  |
|  **HIV-1 group N** |  | **2** | **2**  |
|  **HIV-1 group P** |  | **1** | **1**  |
|  **HIV-2** |  | **122** | **122**  |
|  **Total** |  | **631** | **631**  |

CRF = circulating recombinant form; URF = unique recombinant form; N/A = Not Applicable

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## D. Antigen Analytical Sensitivity

The analytical sensitivity of the HIV Combo Next assay was evaluated on the Alinity i system. Antigen sensitivity was conducted using 3 lots of HIV Combo Next Reagents with the WHO First International Standard for HIV-1 p24 antigen (NIBSC code: 90/636). The HIV-1 p24 antigen analytical sensitivity results ranged from 0.30 to 0.33 IU/mL.

## E. Seroconversion Sensitivity

To determine the seroconversion sensitivity, 39 seroconversion panels obtained from commercial vendors were tested on the Alinity i system using the HIV Combo Next assay. The panel results were evaluated against a commercially available HIV Ag/Ab combination assay and data are summarized below in Table 8.

The HIV Combo Next assay demonstrated an equal or better seroconversion sensitivity, detecting 4 of the 39 evaluated panels as reactive ahead and 35 panels equal to a commercially available HIV Ag/Ab combination assay.

Table 8. Seroconversion Sensitivity of HIV Combo Next

|  Panel ID | Number of Panel Members | Number of Days to First Reactive Result |   | Difference in Number of Bleeds (+/-)^{a}  |
| --- | --- | --- | --- | --- |
|   |   |  HIV Combo Next | Commercially Available HIV Ag/Ab Combo Assay  |   |
|  Zepto6244 | 13 | 28 | 28 | 0  |
|  Zepto6248 | 7 | 18 | 18 | 0  |
|  Zepto9011 | 11 | 38 | 38 | 0  |
|  Zepto9012 | 8 | 16 | 16 | 0  |
|  Zepto9013 | 7 | 25 | 25 | 0  |
|  Zepto9016 | 10 | 30 | 30 | 0  |
|  Zepto9017^{b} | 11 | 21 | 28 | -2  |
|  Zepto9018 | 10 | 28 | 28 | 0  |
|  Zepto9020 | 22 | 90 | 90 | 0  |
|  Zepto9021 | 17 | 47 | 47 | 0  |
|  Zepto9022 | 7 | 23 | 25 | -1  |
|  Zepto9023 | 22 | 78 | 78 | 0  |
|  Zepto9024 | 12 | 53 | 53 | 0  |
|  Zepto9025 | 12 | 85 | 85 | 0  |
|  Zepto9028 | 7 | 53 | 53 | 0  |
|  Zepto9029 | 12 | 45 | 45 | 0  |
|  Zepto9030 | 16 | 47 | 47 | 0  |
|  Zepto9031 | 19 | 146 | 146 | 0  |
|  Zepto9032 | 14 | 22 | 24 | -1  |
|  Zepto9076 | 9 | 66 | 66 | 0  |

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|  Panel ID | Number of Panel Members | Number of Days to First Reactive Result |   | Difference in Number of Bleeds (+/-)^{a}  |
| --- | --- | --- | --- | --- |
|   |   |  HIV Combo Next | Commercially Available HIV Ag/Ab Combo Assay  |   |
|  Zepto9077 | 23 | 45 | 45 | 0  |
|  Zepto9081 | 4 | 24 | 24 | 0  |
|  Zepto9082 | 4 | 13 | 13 | 0  |
|  Zepto9084 | 4 | 49 | 49 | 0  |
|  Zepto9089 | 6 | 16 | 16 | 0  |
|  Zepto9096 | 6 | 3 | 3 | 0  |
|  Zepto12007 | 9 | 117 | 117 | 0  |
|  Zepto12008 | 13 | 28 | 28 | 0  |
|  PRB949 | 4 | 18 | 18 | 0  |
|  PRB950 | 4 | 18 | 18 | 0  |
|  PRB964 | 6 | 22 | 22 | 0  |
|  PRB966 | 10 | 44 | 44 | 0  |
|  PRB969 | 10 | 63 | 63 | 0  |
|  PRB970 | 4 | 0 | 0 | 0  |
|  PRB971 | 4 | 7 | 7 | 0  |
|  PRB973 | 4 | 7 | 7 | 0  |
|  PRB974 | 4 | 9 | 9 | 0  |
|  PRB976 | 4 | 2 | 7 | -1  |
|  PRB978 | 7 | 33 | 33 | 0  |

$^{a}$ 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 investigational assay.

$^{b}$ This sample was reactive on Day 0 (Bleed 1) on the HIV Combo Next assay, nonreactive on bleeds 2-6 (days 3-17), and reactive on bleeds 7 and later (days 21-35). On the commercially available HIV Ag/Ab combination assay, bleed 9 (day 28) was the first reactive bleed.

### F. Analytical Specificity/Interference

Potentially Interfering Endogenous Substances and Potentially Interfering Drugs

Studies were performed based on guidance from CLSI EP07, 3rd ed*. Each substance was evaluated at 2 levels of the analyte (approximately 0.80 S/CO and 1.20 S/CO) in HIV Ab and HIV Ag samples.

No significant interference was observed at the following concentrations listed in Table 9.

* Clinical and Laboratory Standards Institute (CLSI). Interference Testing in Clinical Chemistry. 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI; 2018.

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Table 9. Performance of HIV Combo Next in Presence of Interfering Substances

|  Potentially Interfering Endogenous Substance | Interferent Level  |
| --- | --- |
|  Conjugated Bilirubin | 60 mg/dL  |
|  Unconjugated Bilirubin | 60 mg/dL  |
|  Hemoglobin | 1000 mg/dL  |
|  Total Protein | 15 g/dL  |
|  Triglycerides | 1500 mg/dL  |

|  Potentially Interfering Drug | Interferent Level  |
| --- | --- |
|  Acetaminophen | 200 mg/L  |
|  Acetylcysteine | 300 mg/L  |
|  Acetylsalicylic acid | 1000 mg/L  |
|  Amoxicillin | 54 mg/L  |
|  Ampicillin-Na | 1000 mg/L  |
|  Ascorbic Acid | 300 mg/L  |
|  Biotin | 4250 ng/mL  |
|  Ca-Dobesilate | 200 mg/L  |
|  Cefoxitin | 6600 mg/L  |
|  Cyclosporine | 5 mg/L  |
|  Doxycycline | 50 mg/L  |
|  Heparin | 5000 U/L  |
|  Ibuprofen | 500 mg/L  |
|  Levodopa | 20 mg/L  |
|  Methyldopa | 8.0 mg/L  |
|  Metronidazole | 200 mg/L  |
|  Phenylbutazone | 400 mg/L  |
|  Rifampicin | 60 mg/L  |
|  Tetracycline | 50 mg/L  |
|  Theophylline | 100 mg/L  |
|  Dolutegravir | 0.192 mg/L*  |
|  Lamivudine | 10.5 mg/L*  |
|  Tenofovir | 0.978 mg/L*  |

*Fixed-dose combination

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## G. Cross Reactivity

The HIV Combo Next assay was evaluated for potential interference using specimens from individuals with other disease states or medical conditions unrelated to HIV infection. The HIV Combo Next assay on the Alinity i system and a commercially available HIV Ag/Ab combination assay evaluated 358 specimens from 36 other disease state categories. Of the 358 specimens, 2 were repeatedly reactive and confirmed HIV positive by supplemental testing. All remaining 356 specimens were nonreactive. The results are shown in Table 10.

Table 10. Performance of HIV Combo Next in Other Disease State Specimens

|  Category | N | Commercially Available HIV Ag/Ab Combination Assay Final Interpretation  |   |   |   |
| --- | --- | --- | --- | --- | --- |
|   |   |  Nonreactive |   | Reactive  |   |
|   |   |  HIV Combo Next Final Interpretation |   | HIV Combo Next Final Interpretation  |   |
|   |   |  Nonreactive | Reactive | Nonreactive | Reactive  |
|  Anti-Escherichia coli (E.coli) | 10 | 10 | 0 | 0 | 0  |
|  Antinuclear Antibodies (ANA) | 10 | 10 | 0 | 0 | 0  |
|  Chlamydia (C. trachomatis) | 10 | 10 | 0 | 0 | 0  |
|  Common Cold (Rhinovirus IgG) | 10 | 10 | 0 | 0 | 0  |
|  Cytomegalovirus (CMV) IgG | 10 | 10 | 0 | 0 | 0  |
|  People who Inject Drugs | 11 | 10 | 0 | 0 | 1^{a}  |
|  Epstein-Barr Virus (EBV) | 10 | 10 | 0 | 0 | 0  |
|  Fungal Infections (C. albicans) | 7 | 7 | 0 | 0 | 0  |
|  Gonococcus (N. gonorrhea) | 10 | 10 | 0 | 0 | 0  |
|  Graves' Disease (TRAb) | 10 | 10 | 0 | 0 | 0  |
|  Hemodialysis Patients | 10 | 10 | 0 | 0 | 0  |
|  Hepatitis A Virus (HAV) | 10 | 10 | 0 | 0 | 0  |
|  Hepatitis B Virus (HBV) | 10 | 10 | 0 | 0 | 0  |
|  Hepatitis C Virus (HCV) | 10 | 10 | 0 | 0 | 0  |
|  Herpes Simplex Virus (HSV) | 10 | 10 | 0 | 0 | 0  |
|  Human Anti-Mouse Antibodies (HAMA) | 10 | 10 | 0 | 0 | 0  |
|  Human T-Lymphotropic Virus (HTLV) 1 | 11 | 10 | 0 | 0 | 1^{a}  |
|  Influenza Vaccine Recipients | 10 | 10 | 0 | 0 | 0  |

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|  Category | N | Commercially Available HIV Ag/Ab Combination Assay Final Interpretation  |   |   |   |
| --- | --- | --- | --- | --- | --- |
|   |   |  Nonreactive |   | Reactive  |   |
|   |   |  HIV Combo Next Final Interpretation |   | HIV Combo Next Final Interpretation  |   |
|   |   |  Nonreactive | Reactive | Nonreactive | Reactive  |
|  Monoclonal Hyper IgG | 10 | 10 | 0 | 0 | 0  |
|  Monoclonal Hyper IgM | 9 | 9 | 0 | 0 | 0  |
|  Multiparous Females | 10 | 10 | 0 | 0 | 0  |
|  Multiple Transfusion Recipients | 10 | 10 | 0 | 0 | 0  |
|  Nonspecific Heterophile Antibodies | 10 | 10 | 0 | 0 | 0  |
|  Polyclonal Hyper IgG | 10 | 10 | 0 | 0 | 0  |
|  Polyclonal Hyper IgM | 10 | 10 | 0 | 0 | 0  |
|  Pregnancy First Trimester | 10 | 10 | 0 | 0 | 0  |
|  Pregnancy Second Trimester | 10 | 10 | 0 | 0 | 0  |
|  Pregnancy Third Trimester | 10 | 10 | 0 | 0 | 0  |
|  Rheumatoid Factor (RF) | 10 | 10 | 0 | 0 | 0  |
|  Rubella IgG | 10 | 10 | 0 | 0 | 0  |
|  Smallpox Vaccine Recipients | 10 | 10 | 0 | 0 | 0  |
|  Specimens collected post-mortem (Cadaveric Specimens) | 10 | 10 | 0 | 0 | 0  |
|  Syphilis (T. pallidum) | 10 | 10 | 0 | 0 | 0  |
|  Systemic Lupus Erythematosus (SLE) | 10 | 10 | 0 | 0 | 0  |
|  Toxoplasma gondii | 10 | 10 | 0 | 0 | 0  |
|  Varicella Zoster Virus (VZV) | 10 | 10 | 0 | 0 | 0  |
|  Total | 358 | 356 | 0 | 0 | 2  |

*Specimen was repeatedly reactive and was confirmed HIV positive by supplemental testing.

### H. Tube Type Equivalence

The following tube types were evaluated for use with the HIV Combo Next assay:

- Serum: serum and serum separator tubes
- Plasma: sodium heparin, lithium heparin, lithium heparin separator, tripotassium EDTA, dipotassium EDTA, and dipotassium EDTA plasma separator

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The positive percent agreement (PPA) and negative percent agreement (NPA) ranged from 96.67% to 100.00% when comparing HIV antigen spiked or negative samples and HIV antibody spiked or negative samples collected in the control tube (serum) to the same specimens collected in the evaluation tube types.

All 7 evaluation tube types were found to be equivalent and acceptable for use with the HIV Combo Next assay. The PPA and NPA for each evaluated tube type spiked with HIV antigen, HIV antibody, or negative for HIV are presented in Table 11.

**Table 11. Results of Tube Type Equivalency Study**

|  Evaluation Tube Type | Spiked with Antigen or Negative for HIV (%) |   | Spiked with HIV-1 Group M, HIV-2, and HIV-1 Group O Antibodies or Negative for HIV (%)  |   |
| --- | --- | --- | --- | --- |
|   |  PPA | NPA | PPA | NPA  |
|  Serum separator tube | 100.00 (29/29) | 96.67^{a} (29/30) | 100.00 (30/30) | 100.00 (30/30)  |
|  Sodium heparin | 100.00 (29/29) | 100.00 (30/30) | 100.00 (30/30) | 100.00 (30/30)  |
|  Lithium heparin | 100.00 (29/29) | 100.00 (30/30) | 100.00 (30/30) | 100.00 (30/30)  |
|  Lithium heparin plasma separator | 100.00 (29/29) | 100.00 (30/30) | 100.00 (30/30) | 100.00 (30/30)  |
|  Tripotassium EDTA | 100.00 (29/29) | 100.00 (30/30) | 100.00 (30/30) | 100.00 (30/30)  |
|  Dipotassium EDTA | 100.00 (29/29) | 100.00 (30/30) | 100.00 (30/30) | 100.00 (30/30)  |
|  Dipotassium EDTA plasma separator | 100.00 (29/29) | 100.00 (30/30) | 96.67^{b} (29/30) | 100.00 (30/30)  |

$^{a}$ A discordant sample for high negative (near and below the cutoff) was identified when tested with the serum separator tube type.

$^{b}$ A discordant sample for low-positive (near and above the cutoff) was identified when tested with the dipotassium EDTA plasma separator tube type.

Note: The antigen PPA evaluation was based on 29 samples because 1 sample result was removed due to not meeting the S/CO inclusion range for the control condition.

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# I. Reagent, Calibrator, and Control Stability

The stability of the HIV Combo Next Reagent Kit, Calibrator, and Controls was evaluated using real-time (reagent) and isochronous (calibrator/controls) study designs per CLSI EP25-A (Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline. CLSI Document EP25-A. Wayne, PA: CLSI; 2009). For the reagent, 4 lots (3 2×100 test kits and 1 2×600 test kit) were evaluated for Intended Storage (IS) at 2–8°C and On-Board Storage (OBS), For Intended Use (IU) and Transport Temperature Simulation (both baseline and bi-monthly stress), 1 lot 2×200 test kit and 1 lot 2×600 test kit were evaluated and 1 lot 2×100 test kit was evaluated for Inverted (INV). Testing was conducted at monthly intervals over 15 months (0 – 15 months) for IS and approximately bi-monthly for all other stability conditions. Reference materials, including negative and positive controls, HIV-1/HIV-2/Group O/p24 Ag low-positive panels, a p24 Ag moderate-positive panel, and cluster panels (cluster panels for IS only), were tested up to 9 replicates per run. For the calibrator and controls, 3 lots were evaluated under IS, 2 lots under Transport (1 lot was used for Transport at Baseline and 1 lot was used for Transport Quarterly) and 1 lot under IU (stress before and after freeze) and INV over 15 months (14 months for Transport at Baseline and Transport Quarterly) using an isochronous design. The results support 13 months of expiration dating when stored at 2–8°C for the HIV Combo Next Reagent Kit, and 14 months of expiration dating for the HIV Combo Next Calibrator and Controls. Similarly, the inverted storage and intended use stability results support 13 months of expiration dating for the HIV Combo Next Reagent Kit, and 14 months of expiration dating for the HIV Combo Next Calibrator and Control. For Transport stability, the onboard stability testing performed at various intervals demonstrated that the results support the conclusion that the assay performance is not affected by temperatures up to 40°C when stored up to 11 days during transport. On-board stability of the reagent was demonstrated for up to 30 days at room temperature, In-use stability was demonstrated for up to 24 hours for calibrators and up to 16 hours for controls at room temperature.

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## J. Specimen Storage

The specimen storage study evaluated the stability of serum and plasma specimens tested with the HIV Combo Next assay under various storage conditions and time points. A total of 14 sample sets were collected from healthy donors (Abbott Laboratories, Illinois) in 8 blood collection tube types: serum (plastic), serum separator (plastic), dipotassium EDTA, tripotassium EDTA, lithium heparin, sodium heparin, lithium heparin plasma separator, and dipotassium EDTA plasma separator. Specimens were categorized into 3 analyte groups: unspiked (negative; 0.00 to 0.99 S/CO), HIV antibody-spiked (1.00 to 2.50 S/CO), and HIV antigen-spiked (1.00 to 2.50 S/CO), with spike volumes not exceeding 1% of the sample matrix volume. Storage conditions evaluated included room temperature (30°C for ≥ 3 days), refrigerated (2–8°C for ≥ 7 days), and freeze/thaw cycling (up to 6 cycles at ≤–20°C following refrigeration). Baseline testing was performed within 8 hours of draw in triplicate on a single Alinity i instrument (2 instruments total across the study), using 1 reagent lot, 1 calibrator lot, and 1 control lot.

The study supported specimen storage claims for the HIV Combo Next assay on the Alinity i platform of up to 3 days at room temperature (15–30°C), up to 7 days at 2–8°C (on or off the clot/cells/gel), and up to 6 freeze/thaw cycles when stored at ≤–20°C following refrigeration at 2–8°C.

## K. Specimen Storage (Frozen)

The stability of serum and plasma specimens tested with the HIV Combo Next assay following frozen storage at -20°C (range: -10°C to -20°C) and -70°C or colder for up to 4 months (124 days) was evaluated. Specimens were sourced from 12 donors per collection tube type in 8 blood collection tube types (serum plastic, serum separator [plastic], dipotassium EDTA, tripotassium EDTA, lithium heparin, sodium heparin, lithium heparin [plasma separator], and dipotassium EDTA [plasma separator]). Each specimen was split into 3 aliquots: unspiked (Analyte Level A; target < 1.00 S/CO), spiked with HIV antibody (Analyte Level B; target 1.00 to 2.50 S/CO), and spiked with HIV p24 antigen (Analyte Level C; target 1.00 to

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2.50 S/CO). Aliquots were tested in duplicate at baseline and at 3 post-storage time points (≥ 31, ≥ 93, and ≥ 124 days). The study supports the use of serum and plasma specimens stored at ≤ -20°C and ≤ -70°C respectively for up to 3 months.

### L. Sample Onboard Storage

The stability of samples stored on the Alinity i system (onboard storage) and tested with the HIV Combo Next assay was evaluated using 9 samples, including negative and positive controls, as well as HIV-1 antibody and HIV-1 p24 antigen high-negative and low-positive panels, all prepared in recalcified plasma (with the exception of one positive control, which was prepared in a buffer matrix). Using an isochronous design, samples were tested at 2 time points: a baseline (samples stored at 2 to 8°C off the instrument and loaded immediately prior to testing) and a 3-hour onboard time point (samples stored on the instrument's Reagent and Sample Manager [RSM] for ≥ 3 hours prior to testing). Each sample was tested in 11 replicates (single replicate per sample cup) using 1 instrument, 1 reagent lot, 1 calibrator lot, and 1 control lot. The results demonstrated that samples can be stored onboard the Alinity i system for up to 3 hours at room temperature without affecting assay performance.

### M. Carryover

The within-assay sample carryover study was performed to evaluate the susceptibility of the HIV Combo Next assay to carryover from high-level HIV antibody and HIV-1 p24 antigen samples. Testing was performed separately for antibody and antigen carryover on a single Alinity i instrument using 1 reagent lot, 1 calibrator lot, and 1 control lot. For each assessment, a high-negative sample (targeted to 0.60 to 0.99 S/CO) was tested both as a "protected" sample (tested prior to a high-positive sample) and as an "unprotected" sample (tested immediately after the high-positive sample), with 3 wash buffer replicates preceding each iteration to clear the system. High-positive antibody samples consisted of 10 individual anti-HIV-1 serum and plasma specimens (≥ 500 S/CO), tested across 11 iterations in 5 runs; high-positive antigen samples were HIV-1 p24 antigen in negative

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recalcified human plasma ($\geq 500$ S/CO), tested across 12 iterations in 5 runs. The carryover effect was quantified as the difference in mean S/CO between the unprotected and protected samples, with a two-sided 95% confidence interval (CI) calculated for both the difference and percent difference. The upper limit of the two-sided 95% CI for the difference was less than +0.20 S/CO for both antibody and antigen samples. The HIV Combo Next assay demonstrated acceptable within-assay sample carryover.

## **N. High Dose Hook Effect Study**

High dose hook effect was not observed on samples up to 539 S/CO for HIV antibody and 585 S/CO for HIV antigen.

The S/CO results of the serial dilutions of high-positive anti-HIV-1, anti-HIV-2, and anti-HIV-1 group O antibody samples and high-positive HIV-1 p24 antigen samples increased with increasing relative concentration for all dilutions.

## **O. Summary of Clinical Performance**

### **1. Reproducibility**

This study was performed based on guidance from CLSI EP05-A3\*. Testing was conducted at each of the 3 testing sites using 3 lots of the HIV Combo Next reagents, 3 lots of the HIV Combo Next Calibrator, 3 lots of the HIV Combo Next Controls, and one instrument. Five controls and 7 recalcified human plasma panels were tested in 4 replicates 2 times per day over 5 days. The results supported the conclusion that the HIV Combo Next was reproducible within run, between run, between days, between sites, and between lots. The performance is shown in Table 12.

\* Clinical and Laboratory Standards Institute (CLSI). *Evaluation of Precision of Quantitative Measurement Procedures: Approved Guideline–Third Edition*. CLSI Document EP05-A3. Wayne, PA: CLSI; 2014.

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**Table 12. Reproducibility Results for HIV Combo Next**

|  Sample | n | Mean (S/CO) | Repeatability (Within-Run) |   | Between-Run |   | Between-Day |   | Within-Laboratory^{a} |   | Between-Site |   | Between-Lot |   | Overall Reproducibility^{b}  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV  |
|  Negative Control | 360 | 0.10 | 0.007 | 7.2 | 0.002 | 2.4 | 0.003 | 3.3 | 0.008 | 8.3 | 0.007 | 7.0 | 0.015 | 15.1 | 0.019 | 18.6  |
|  Positive Control 1 | 360 | 3.30 | 0.122 | 3.7 | 0.035 | 1.0 | 0.034 | 1.0 | 0.131 | 4.0 | 0.163 | 4.9 | 0.073 | 2.2 | 0.221 | 6.7  |
|  Positive Control 2 | 360 | 1.89 | 0.052 | 2.8 | 0.026 | 1.4 | 0.012 | 0.6 | 0.059 | 3.1 | 0.063 | 3.3 | 0.092 | 4.9 | 0.127 | 6.7  |
|  Positive Control 3 | 360 | 1.96 | 0.033 | 1.7 | 0.014 | 0.7 | 0.025 | 1.3 | 0.044 | 2.2 | 0.022 | 1.1 | 0.018 | 0.9 | 0.052 | 2.7  |
|  Positive Control 4 | 360 | 2.38 | 0.080 | 3.4 | 0.021 | 0.9 | 0.031 | 1.3 | 0.088 | 3.7 | 0.093 | 3.9 | 0.057 | 2.4 | 0.140 | 5.9  |
|  HIV-1 Ab Low-Positive Panel | 360 | 1.23 | 0.041 | 3.3 | 0.017 | 1.4 | 0.020 | 1.6 | 0.048 | 3.9 | 0.046 | 3.7 | 0.085 | 6.9 | 0.108 | 8.7  |
|  HIV-2 Ab Low-Positive Panel | 360 | 1.09 | 0.031 | 2.9 | 0.010 | 0.9 | 0.015 | 1.4 | 0.036 | 3.3 | 0.076 | 7.0 | 0.047 | 4.3 | 0.097 | 8.8  |
|  HIV-1 gO Ab Low-Positive Panel | 360 | 1.22 | 0.044 | 3.6 | 0.021 | 1.7 | 0.000 | 0.0 | 0.048 | 4.0 | 0.015 | 1.3 | 0.128 | 10.5 | 0.138 | 11.3  |
|  HIV-1 p24 Ag Low-Positive Panel | 360 | 1.20 | 0.036 | 3.0 | 0.006 | 0.5 | 0.009 | 0.7 | 0.038 | 3.1 | 0.037 | 3.1 | 0.012 | 1.0 | 0.054 | 4.5  |
|  HIV-1 p24 Ag High Negative Panel | 360 | 0.78 | 0.021 | 2.7 | 0.009 | 1.2 | 0.005 | 0.6 | 0.023 | 3.0 | 0.032 | 4.2 | 0.011 | 1.4 | 0.041 | 5.3  |
|  HIV-1 Ab High Negative Panel | 360 | 0.80 | 0.031 | 3.9 | 0.007 | 0.9 | 0.012 | 1.5 | 0.034 | 4.2 | 0.043 | 5.4 | 0.054 | 6.8 | 0.078 | 9.7  |
|  HIV-1 p24 Ag Moderate Positive Panel | 360 | 2.40 | 0.064 | 2.7 | 0.026 | 1.1 | 0.017 | 0.7 | 0.071 | 3.0 | 0.072 | 3.0 | 0.017 | 0.7 | 0.103 | 4.3  |

$^{a}$ Includes repeatability (within-run), between-run, and between-day variability.

$^{b}$ Includes repeatability (within-run), between-run, between-day, between-site, and between-lot variability.

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## 2. Clinical Performance

A multicenter study was conducted to demonstrate the performance of the HIV Combo Next assay with specimens from the intended use population in a clinical laboratory setting. A total of 10,063 serum or plasma samples were included in the analysis:

- 1964 antibody- positive samples
  - 1729 HIV-1 antibody positive, consisting of group M subtypes A to L, group O, CRFs, and URFs; including 76 specimens from pregnant females and 79 specimens from pediatric subjects
  - 235 HIV-2 antibody positive
- 101 antigen positive samples, consisting of HIV-1 p24 antigen and HIV-1 and HIV-2 viral isolates
- 1573 specimens from individuals at increased risk of HIV infection, including 193 from pregnant females, 78 from pediatric subjects, and 535 from HIV-2 endemic areas. Risk factors for HIV infection include the following:
  - Sexual contact with person(s) infected with HIV
  - Unprotected sex with HIV-infected or high-risk individuals
  - Men who have sex with men
  - Multiple sex partners
  - User of injection drugs
  - Recently diagnosed or treated for a sexually transmitted disease (STD) or tuberculosis (TB)
  - Unprotected sex with individuals diagnosed or treated for STD
  - Sexual contact with person(s) infected with HAV, HBV, or HCV
  - History of STD
  - History of incarceration
  - Transplant recipient prior to July 1992
  - Tattoo, body piercing, or acupuncture
  - Occupational exposure
  - Hemodialysis patients
  - Perinatal exposure to HBV or HCV
  - Household exposure to individuals infected with HIV
  - Recent fever or illness of unknown origin

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- 6425 specimens from individuals at low risk of HIV infection (from clinical settings with an HIV prevalence of ≤ 1%), including 288 from pregnant females

One replicate of each specimen was tested with the HIV Combo Next assay. Specimens with an initial reactive result were retested in duplicate. Except for known positives, samples with a final interpretation of reactive were further tested using 2 supplemental FDA-cleared/approved HIV-1/HIV-2 assays to determine final status per the CDC HIV testing algorithm*.

### Sensitivity

The clinical sensitivity of the HIV Combo Next assay was evaluated using a total of 2137 specimens with a final status confirmed as HIV positive. These specimens included 1729 HIV-1 antibody positive samples, 235 HIV-2 antibody-positive samples, 101 HIV-1/HIV-2 antigen positive samples, and 72 confirmed positive specimens collected from individuals at increased risk of HIV infection. The overall sensitivity of the HIV Combo Next assay was **100.00% (2137/2137) with a 95% CI of 99.83% to 100.00%** (Table 13).

**Table 13. Overall Clinical Sensitivity of HIV Combo Next**

|  Specimen Category | n | R | NR | Sensitivity (%) | 95% CI  |
| --- | --- | --- | --- | --- | --- |
|  **HIV-1 Antibody Positive (Overall)** | 1729 | 1729 | 0 | 100.00 | (99.79, 100.00)  |
|  HIV-1 Ab Positive Specimens | 1186 | 1186 | 0 | 100.00 | (99.69, 100.00)  |
|  HIV-1 Ab Panel Samples | 388 | 388 | 0 | 100.00 | (99.05, 100.00)  |
|  HIV-1 Ab Positive – Pediatric | 79 | 79 | 0 | 100.00 | (95.44, 100.00)  |
|  HIV-1 Ab Positive – Pregnant Females | 76 | 76 | 0 | 100.00 | (95.26, 100.00)  |
|  **HIV-2 Antibody Positive (Overall)** | 235 | 235 | 0 | 100.00 | (98.44, 100.00)  |
|  HIV-2 Ab Positive Specimens | 226 | 226 | 0 | 100.00 | —  |

* Centers for Disease Control and Prevention (CDC). Sexually Transmitted Infections Treatment Guidelines, 2021. HIV infection: detection, counseling, and referral. Updated July 22, 2021. Accessed June 25, 2026. https://www.cdc.gov/std/treatment-guidelines/hiv.htm

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|  Specimen Category | n | R | NR | Sensitivity (%) | 95% CI  |
| --- | --- | --- | --- | --- | --- |
|  HIV-2 Ab Panel Samples | 9 | 9 | 0 | 100.00 | —  |
|  **HIV-1/-2 Antigen Positive (Overall)** | 101 | 101 | 0 | 100.00 | (96.41, 100.00)  |
|  HIV-1 Antigen Viral Isolates | 36 | 36 | 0 | 100.00 | —  |
|  HIV-1 p24 Antigen | 56 | 56 | 0 | 100.00 | —  |
|  HIV-2 Antigen Viral Isolates | 9 | 9 | 0 | 100.00 | —  |
|  **Confirmed Positives from Increased Risk Population** | 72 | 72 | 0 | 100.00 | (95.01, 100.00)  |
|  **Overall Sensitivity (HIV Positive + Confirmed Positives)** | **2137** | **2137** | **0** | **100.00** | **(99.83, 100.00)**  |

R = Reactive, NR = Nonreactive

### Specificity

The clinical specificity of the HIV Combo Next assay was evaluated using a total of 7998 specimens that included 6425 samples from individuals at low risk of HIV infection and 1573 samples from individuals at increased risk of HIV infection. The overall specificity of the HIV Combo Next assay was **99.67% (7,865, 7,891) with a 95% CI of 99.52% to 99.78%** (Table 14).

**Table 14. Overall Clinical Specificity of HIV Combo Next**

|  Population | n | Final HIV Negative |   |   | Specificity (%) | 95% CI  |
| --- | --- | --- | --- | --- | --- | --- |
|   |   |  Total | NR | R  |   |   |
|  **Individuals at Low Risk – Overall** | 6425 | 6390 | 6374 | 16 | 99.75 | (99.59, 99.86)  |
|  Low Risk (Frozen) | 5537 | 5505 | 5490 | 15 | 99.73 | (99.55, 99.85)  |
|  Low Risk (Fresh) | 600 | 597 | 597 | 0 | 100.00 | (99.38, 100.00)  |
|  Low Risk – Pregnant Females | 288 | 288 | 287 | 1 | 99.65 | (98.08, 99.99)  |

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|  Population | n | Final HIV Negative |   |   | Specificity (%) | 95% CI  |
| --- | --- | --- | --- | --- | --- | --- |
|   |   |  Total | NR | R  |   |   |
|  **Individuals at Increased Risk – Overall** | 1573 | 1501 | 1491 | 10 | 99.33 | (98.78, 99.68)  |
|  Increased Risk | 767 | 740 | 737 | 3 | 99.59 | (98.82, 99.92)  |
|  Increased Risk – Pregnant Females | 193 | 193 | 193 | 0 | 100.00 | (98.11, 100.00)  |
|  Increased Risk – Pediatric | 78 | 78 | 78 | 0 | 100.00 | (95.38, 100.00)  |
|  Increased Risk – HIV-2 Endemic Areas | 535 | 490 | 483 | 7 | 98.57 | (97.08, 99.42)  |
|  **Overall Clinical Specificity (Low Risk and Increased Risk combined)** | **7998** | **7891** | **7865** | **26** | **99.67** | **(99.52, 99.78)**  |

R = Reactive, NR = Nonreactive

### Sensitivity and Specificity in the Individual Cohorts

The detailed results for each of the individual cohorts are presented below.

#### HIV-1 Antibody Positive

This study cohort included both HIV-1 antibody positive specimens and HIV-1 antibody positive panels. HIV-1 antibody positive samples included 1186 specimens collected in the U.S. and Cameroon, while the HIV-1 antibody positive panels included 339 HIV-1 group M antibody positive panel samples that originated in Cameroon, Thailand, Brazil, South Africa, Ghana, Senegal, Argentina, Saudi Arabia, Republic of the Congo, Kinshasa, and Spain and 49 HIV-1 group O antibody positive panel samples that originated in Cameroon, Equatorial Guinea, Spain, and the U.S.

The sensitivity of the HIV Combo Next assay for HIV-1 antibody positive specimens and panel samples is shown in Table 15. Additional HIV-1 antibody

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positive specimens are included in the Pediatric Population and Pregnant Females sections below.

**Table 15. Clinical Sensitivity of HIV Combo Next in HIV-1 Ab Positive Specimen and HIV-1 Ab Positive Panel Samples**

|  Specimen Category | n | Final HIV Status |   | Sensitivity (%) (95% CI)  |
| --- | --- | --- | --- | --- |
|   |   |  Positive  |   |   |
|   |   |  R | NR  |   |
|  HIV-1 Ab Positive Specimens | 1186 | 1186 | 0 | 100.00 (1186/1186) (99.69, 100.00)  |
|  HIV-1 Ab Panel Samples | 388 | 388 | 0 | 100.00 (388/388) (99.05, 100.00)  |

R = Reactive, NR = Nonreactive

The reactivity of the HIV Combo Next assay for all HIV-1 antibody positive specimens and panel samples was 100.0%. All were initially and repeatedly reactive.

#### HIV-2 Antibody Positive

HIV-2 antibody positive samples included 226 specimens collected in Côte d’Ivoire and 9 HIV-2 antibody positive panel samples that originated in Cameroon.

The sensitivity of the HIV Combo Next assay for HIV-2 antibody positive specimens and panel samples is shown in Table 16.

**Table 16. Clinical Sensitivity of HIV Combo Next in HIV-2 Ab Positive Specimens**

|  Specimen Category | n | Final HIV Status |   | Sensitivity (%) (95% CI)  |
| --- | --- | --- | --- | --- |
|   |   |  Positive  |   |   |
|   |   |  R | NR  |   |
|  HIV-2 Ab Positive Specimens | 235 | 235 | 0 | 100.00 (235/235) (98.44, 100.00)  |

R = Reactive, NR = Nonreactive

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The reactivity of the HIV Combo Next assay for all HIV-2 antibody positive specimens and panel samples was 100.0%. All were initially and repeatedly reactive.

#### HIV-1 and HIV-2 Antigen Positive

The antigen positive samples included 44 HIV-1 p24 antigen positive specimens, 36 HIV-1 viral isolates, 12 WHO 1$^{st}$ International Reference Panel for HIV-1 p24 Antigen (NIBSC code: 16/210) panel samples, and 9 HIV-2 viral isolates.

The sensitivity of the HIV Combo Next assay for HIV-1 and HIV-2 antigen positive specimens and panel samples is shown in Table 17.

**Table 17. Clinical Sensitivity of HIV Combo Next in HIV-1 and HIV-2 Ag Positive Samples**

|  Specimen Category | n | Final HIV Status |   | Sensitivity (%) (95% CI)  |
| --- | --- | --- | --- | --- |
|   |   |  Positive  |   |   |
|   |   |  R | NR  |   |
|  HIV-1 and HIV-2 Ag Positive | 101 | 101 | 0 | 100.00 (101/101) (96.41, 100.00)  |

R = Reactive, NR = Nonreactive

The reactivity of the HIV Combo Next assay for all HIV-1 and HIV-2 antigen positive specimens and panel samples was 100.0%. All were initially and repeatedly reactive.

#### Individuals at Increased Risk of HIV Infection

A total of 1573 specimens from individuals at increased risk of HIV infection were evaluated, including specimens from the pediatric population and pregnant females; 796 (50.6%) were from males and 774 (49.2%) were from females (remainder were reported as other), with a mean age of 36.5 years (range: 2 to 80 years). The population consisted of the following racial groups:

- 986 (62.7%) Black or African American

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- 351 (22.3%) White
- 11 (0.7%) Asian
- 5 (0.3%) More than one race
- 4 (0.3%) American Indian or Alaska Native
- 1 (0.1%) Native Hawaiian or Other Pacific Islander
- 1 (0.1%) Other
- 214 (13.6%) Unknown / not reported

Specimens from individuals at increased risk of HIV infection were collected in the U.S. and in HIV-2 endemic areas (Côte d’Ivoire and Sierra Leone).

The overall sensitivity of the HIV Combo Next assay for specimens from individuals at increased risk of HIV infection was 100.00% (72/72) with a 95% CI of 95.01% to 100.00%. The overall specificity of the HIV Combo Next assay for specimens from individuals at increased risk of HIV infection was 99.33% (1491/1501) with a 95% CI of 98.78% to 99.68%.

The sensitivity and specificity of the HIV Combo Next assay for specimens from individuals at increased risk of HIV infection by specimen category and matrix are shown in Table 18. Specimens from the pediatric population and pregnant females at increased risk of HIV infection are included in the Pediatric Population and Pregnant Females sections below.

Table 18. Clinical Sensitivity and Specificity of HIV Combo Next in Individuals at Increased Risk of HIV Infection

|  Specimen Category | Matrix | n | Final HIV Status |   |   |   | Sensitivity (%) (95% CI) | Specificity (%) (95% CI)  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  Positive |   | Negative  |   |   |   |
|   |   |   |  R | NR | R | NR  |   |   |
|  Increased Risk of HIV (U.S.) | Serum | 398 | 26 | 0 | 0 | 372 | 100.00 (26/26) (86.77, 100.00) | 100.00 (372/372) (99.01, 100.00)  |
|   |  Plasma | 369 | 1 | 0 | 3 | 365 | 100.00 (1/1) (2.50, 100.00) | 99.18 (365/368) (97.64, 99.83)  |
|   |  Total (Serum and Plasma) | 767 | 27 | 0 | 3 | 737 | 100.00 (27/27) (87.23, 100.00) | 99.59 (737/740) (98.82, 99.92)  |

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|  Specimen Category | Matrix | n | Final HIV Status |   |   |   | Sensitivity (%) (95% CI) | Specificity (%) (95% CI)  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  Positive |   | Negative  |   |   |   |
|   |   |   |  R | NR | R | NR  |   |   |
|  HIV-2 Endemic Areas | Plasma | 535 | 45 | 0 | 7 | 483 | 100.00 (45/45) (92.13, 100.00) | 98.57 (483/490) (97.08, 99.42)  |

R = Reactive, NR = Nonreactive

The reactivity results of the HIV Combo Next assay for specimens from individuals at increased risk of HIV infection by matrix are shown in Table 19.

**Table 19. Reactivity of HIV Combo Next in Individuals at Increased Risk of HIV Infection**

|  Specimen Category | Matrix | n | Number of NR (%) | Number of IR (%) | Number of RR (%) | Number of Confirmed Positive^{a} (%)  |
| --- | --- | --- | --- | --- | --- | --- |
|  Increased Risk of HIV (U.S.) | Serum | 398 | 372 (93.5%) | 26 (6.5%) | 26 (6.5%) | 26 (6.5%)  |
|   |  Plasma | 369 | 365 (98.9%) | 6 (1.6%) | 4 (1.1%) | 1 (0.3%)  |
|   |  Total (Serum and Plasma) | 767 | 737 (96.1%) | 32 (4.2%) | 30 (3.9%) | 27 (3.5%)  |
|  HIV-2 Endemic Areas | Plasma | 535 | 483 (90.3%) | 52 (9.7%) | 52 (9.7%) | 45 (8.4%)  |

NR = Nonreactive, IR = Initially reactive, RR = Repeatedly reactive

$^{a}$Samples with a final interpretation of reactive were further tested using 2 supplemental FDA-cleared/approved HIV-1/HIV-2 assays to determine final status.

### Individuals at Low Risk of HIV Infection

A total of 6425 specimens from individuals at low risk of HIV infection were evaluated, including those from pregnant females; 4508 (70.2%) were from females and 1917 (29.8%) were from males, with a mean age of 41 years (range: 16 to 89 years). The population consisted of the following racial groups:

- 3276 (51.0%) White
- 2150 (33.5%) Black or African American
- 111 (1.7%) Asian
- 61 (0.9%) More than one race
- 23 (0.4%) American Indian or Alaska Native

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- 7 (0.1%) Native Hawaiian or Other Pacific Islander
- 1 (0.0%) Other
- 796 (12.4%) Unknown / not reported

Specimens from individuals at low risk of HIV infection were collected in the U.S.

The overall sensitivity of the HIV Combo Next assay for specimens from individuals at low risk of HIV infection was 100.00% (35/35) with a 95% CI of 90.00% to 100.00%. The overall specificity of the HIV Combo Next assay for specimens from individuals at low risk of HIV infection was 99.75% (6374/6390) with a 95% CI of 99.59% to 99.86%.

The sensitivity and specificity of the HIV Combo Next assay for specimens from individuals at low risk of HIV infection by specimen category and matrix are shown in Table 20. Specimens from pregnant females at low risk of HIV infection are included in the Pregnant Females section below.

Table 20. Sensitivity and Specificity of HIV Combo Next in Individuals at Low Risk of HIV Infection

|  Specimen Category | Matrix | n | Final HIV Status |   |   |   | Sensitivity (%) (95% CI) | Specificity (%) (95% CI)  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  Positive |   | Negative  |   |   |   |
|   |   |   |  R | NR | R | NR  |   |   |
|  Frozen Specimens | Serum | 2551 | 16 | 0 | 11 | 2524 | 100.00 (16/16) (79.41, 100.00) | 99.57 (2524/2535) (99.22, 99.78)  |
|   |  Plasma | 2986 | 16 | 0 | 4 | 2966 | 100.00 (16/16) (79.41, 100.00) | 99.87 (2966/2970) (99.66, 99.96)  |
|   |  Total (Serum and Plasma) | 5537 | 32 | 0 | 15 | 5490 | 100.00 (32/32) (89.11, 100.00) | 99.73 (5490/5505) (99.55, 99.85)  |
|  Fresh Specimens | Plasma | 600 | 3 | 0 | 0 | 597 | 100.00 (3/3) (29.24, 100.00) | 100.00 (597/597) (99.38, 100.00)  |

R = Reactive, NR = Nonreactive

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The reactivity results of the HIV Combo Next assay for specimens from individuals at low risk of HIV infection by specimen category and matrix are shown in Table 21.

**Table 21. Reactivity of HIV Combo Next in Individuals at Low Risk of HIV Infection**

|  Specimen Category | Matrix | n | Number of NR (%) | Number of IR (%) | Number of RR (%) | Number of Confirmed Positive^{a} (%)  |
| --- | --- | --- | --- | --- | --- | --- |
|  Frozen Specimens | Serum | 2551 | 2524 (98.9%) | 31 (1.2%) | 27 (1.1%) | 16 (0.6%)  |
|   |  Plasma | 2986 | 2966 (99.3%) | 28 (0.9%) | 20 (0.7%) | 16 (0.5%)  |
|   |  Total (Serum and Plasma) | 5537 | 5490 (99.2%) | 59 (1.1%) | 47 (0.8%) | 32 (0.6%)  |
|  Fresh Specimens | Plasma | 600 | 597 (99.5%) | 3 (0.5%) | 3 (0.5%) | 3 (0.5%)  |

NR = Nonreactive, IR = Initially reactive, RR = Repeatedly reactive

$^{a}$Samples with a final interpretation of reactive were further tested using 2 supplemental FDA-cleared/approved HIV-1/HIV-2 assays to determine final status.

### Pediatric Population

The sensitivity of the HIV Combo Next assay for HIV-1 antibody positive specimens from the pediatric population is shown in Table 22.

**Table 22. Sensitivity of HIV Combo Next in Pediatric Population**

|  Specimen Category | n | Final HIV Status |   | Sensitivity (%) (95% CI)  |
| --- | --- | --- | --- | --- |
|   |   |  Positive  |   |   |
|   |   |  R | NR  |   |
|  HIV-1 Ab Positive | 79 | 79 | 0 | 100.00 (79/79) (95.44, 100.00)  |

R = Reactive, NR = Nonreactive

The specificity of the HIV Combo Next assay for individuals at increased risk of HIV infection from the pediatric population is shown in Table 23.

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**Table 23. Specificity of HIV Combo Next in Pediatric Population**

|  Specimen Category | n | Final HIV Status |   | Specificity (%) (95% CI)  |
| --- | --- | --- | --- | --- |
|   |   |  Negative  |   |   |
|   |   |  R | NR  |   |
|  Increased Risk of HIV | 78 | 0 | 78 | 100.00 (78/78) (95.38, 100.00)  |

R = Reactive, NR = Nonreactive

The reactivity of the HIV Combo Next assay for specimens from the pediatric population by age range and sex is shown in Table 24.

**Table 24. Reactivity of HIV Combo Next in Pediatric Population**

|  Specimen Category | Age Range (Years) | Sex | n | Number of NR (%) | Number IR (%) | Number of RR (%) | Number of Confirmed Positive^{a} (%)  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  HIV-1 Ab Positive | 2-5 | M | 4 | 0 (0.0%) | 4 (100.0%) | 4 (100.0%) | 4 (100.0%)  |
|   |   |  F | 6 | 0 (0.0%) | 6 (100.0%) | 6 (100.0%) | 6 (100.0%)  |
|   |  6-10 | M | 17 | 0 (0.0%) | 17 (100.0%) | 17 (100.0%) | 17 (100.0%)  |
|   |   |  F | 9 | 0 (0.0%) | 9 (100.0%) | 9 (100.0%) | 9 (100.0%)  |
|   |  11-15 | M | 12 | 0 (0.0%) | 12 (100.0%) | 12 (100.0%) | 12 (100.0%)  |
|   |   |  F | 11 | 0 (0.0%) | 11 (100.0%) | 11 (100.0%) | 11 (100.0%)  |
|   |  16-18 | M | 14 | 0 (0.0%) | 14 (100.0%) | 14 (100.0%) | 14 (100.0%)  |
|   |   |  F | 6 | 0 (0.0%) | 6 (100.0%) | 6 (100.0%) | 6 (100.0%)  |
|   |  All Ages | M | 47 | 0 (0.0%) | 47 (100.0%) | 47 (100.0%) | 47 (100.0%)  |
|   |   |  F | 32 | 0 (0.0%) | 32 (100.0%) | 32 (100.0%) | 32 (100.0%)  |
|  Increased Risk of HIV | 2-5 | M | 7 | 7 (100.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%)  |
|   |   |  F | 12 | 12 (100.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%)  |
|   |  6-10 | M | 15 | 15 (100.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%)  |
|   |   |  F | 15 | 15 (100.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%)  |
|   |  11-15 | M | 11 | 11 (100.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%)  |

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|  Specimen Category | Age Range (Years) | Sex | n | Number of NR (%) | Number IR (%) | Number of RR (%) | Number of Confirmed Positive^{a} (%)  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   | 16-18 | F | 9 | 9 (100.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%)  |
|   |   |  M | 2 | 2 (100.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%)  |
|   |   |  F | 7 | 7 (100.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%)  |
|   |  All Ages | M | 35 | 35 (100.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%)  |
|   |   |  F | 43 | 43 (100.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%)  |

M = Male, F = Female, NR = Nonreactive, IR = Initially reactive, RR = Repeatedly reactive

$^{a}$ Except for known HIV-1 antibody positives, samples with a final interpretation of reactive were further tested using 2 supplemental FDA-cleared/approved HIV-1/HIV-2 assays to determine final status.

### Pregnant Females

The sensitivity of the HIV Combo Next assay for HIV-1 antibody positive specimens from pregnant females by trimester is shown in Table 25.

Table 25. Sensitivity of HIV Combo Next in Pregnant Females

|  Specimen Category | Trimester | n | Final HIV Status |   | Sensitivity (%) (95% CI)  |
| --- | --- | --- | --- | --- | --- |
|   |   |   |  Positive  |   |   |
|   |   |   |  R | NR  |   |
|  HIV-1 Ab Positive | 1 | 14 | 14 | 0 | 100.00 (14/14) (76.84, 100.00)  |
|   |  2 | 37 | 37 | 0 | 100.00 (37/37) (90.51, 100.00)  |
|   |  3 | 25 | 25 | 0 | 100.00 (25/25) (86.28, 100.00)  |
|   |  Overall | 76 | 76 | 0 | 100.00 (76/76) (95.26, 100.00)  |

R = Reactive, NR = Nonreactive

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The specificity of the HIV Combo Next assay for specimens from pregnant females by specimen category and trimester is shown in Table 26.

**Table 26. Specificity of HIV Combo Next in Pregnant Females**

|  Specimen Category | Trimester | n | Final HIV Status |   | Specificity (%) (95% CI)  |
| --- | --- | --- | --- | --- | --- |
|   |   |   |  Negative  |   |   |
|   |   |   |  R | NR  |   |
|  Increased Risk of HIV | 1 | 24 | 0 | 24 | 100.00 (24/24) (85.75, 100.00)  |
|   |  2 | 38 | 0 | 38 | 100.00 (38/38) (90.75, 100.00)  |
|   |  3 | 131 | 0 | 131 | 100.00 (131/131) (97.22, 100.00)  |
|   |  Overall | 193 | 0 | 193 | 100.00 (193/193) (98.11, 100.00)  |
|  Low Risk of HIV | 1 | 288 | 1 | 287 | 99.65 (287/288) (98.08, 99.99)  |
|   |  Overall | 288 | 1 | 287 | 99.65 (287/288) (98.08, 99.99)  |

R = Reactive, NR = Nonreactive

The number of initial reactives, repeat reactives, and confirmed reactives in specimens from pregnant females by specimen category and trimester is summarized below in Table 27.

**Table 27. Reactivity of HIV Combo Next in Pregnant Females**

|  Specimen Category | Trimester | n | Number of NR (%) | Number of IR (%) | Number of RR (%) | Number of Confirmed Positive^{a} (%)  |
| --- | --- | --- | --- | --- | --- | --- |
|  HIV-1 Ab Positive | 1 | 14 | 0 (0.0%) | 14 (100.0%) | 14 (100.0%) | 14 (100.0%)  |
|   |  2 | 37 | 0 (0.0%) | 37 (100.0%) | 37 (100.0%) | 37 (100.0%)  |

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|  Specimen Category | Trimester | n | Number of NR (%) | Number of IR (%) | Number of RR (%) | Number of Confirmed Positive^{a} (%)  |
| --- | --- | --- | --- | --- | --- | --- |
|   | 3 | 25 | 0 (0.0%) | 25 (100.0%) | 25 (100.0%) | 25 (100.0%)  |
|   |  Overall | 76 | 0 (0.0%) | 76 (100.0%) | 76 (100.0%) | 76 (100.0%)  |
|  Increased Risk of HIV | 1 | 24 | 24 (100.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%)  |
|   |  2 | 38 | 38 (100.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%)  |
|   |  3 | 131 | 131 (100.0%) | 1 (0.8%) | 0 (0.0%) | 0 (0.0%)  |
|   |  Overall | 193 | 193 (100.0%) | 1 (0.5%) | 0 (0.0%) | 0 (0.0%)  |
|  Low Risk of HIV | 1 | 288 | 287 (99.7%) | 1 (0.3%) | 1 (0.3%) | 0 (0.0%)  |
|   |  Overall | 288 | 287 (99.7%) | 1 (0.3%) | 1 (0.3%) | 0 (0.0%)  |

NR = Nonreactive, IR = Initially reactive, RR = Repeatedly reactive

$^{a}$ Except for known HIV-1 antibody positives, samples with a final interpretation of reactive were further tested using 2 supplemental FDA-cleared/approved HIV-1/HIV-2 assays to determine final status.

### P. Conclusion Drawn from Nonclinical and Clinical Laboratory Studies

The HIV Combo Next assay is a chemiluminescent microparticle immunoassay (CMIA) used for the simultaneous qualitative detection of human immunodeficiency virus type 1 (HIV-1) p24 antigen and antibodies to HIV-1 group M and O and/or type 2 (HIV-2) in human serum and plasma (EDTA and heparin) on the Alinity i system. The HIV Combo Next assay has the same technology and a similar intended use as the predicate device. The analytical and clinical data presented demonstrate that the device is as safe, as effective, and performs as well as the predicate device.

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**Source:** [https://fda.innolitics.com/device/BK261345](https://fda.innolitics.com/device/BK261345)

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