FDA Logo links to FDA home page
Center for Biologics Evaluation and Research, U.S. Food and Drug AdministrationU.S. Food and Drug AdministrationCenter for Biologics Evaluation and Research
 HHS Logo links to Department of Health and Human Services website

FDA Home Page | CBER A-Z Index | CBER Search | Contact CBER | CBER Home Page

horizonal rule
Blood | Therapeutics | Vaccines | Cellular & Gene Therapy | Allergenics | Tissue | Devices
Products | Manufacturers | Health Professionals | Consumers | Reading Room | Meetings & Workshops | Research | About Us
horizonal rule

SUMMARY OF SAFETY AND EFFECTIVENESS

PMA SHELL REFERENCE BM020040
 
PMA REFERENCE BP020066
 
TITLE OF SUBMISSION VIRONOSTIKA HIV-1 PLUS O MICROELISA SYSTEM
PRE-MARKET APPLICATION
 
PRODUCT NAME VIRONOSTIKA HIV-1 PLUS O MICROELISA SYSTEM
 
MANUFACTURER/SPONSOR bioMérieux, Inc.
 
MANUFACTURER’S ADDRESS 100 Rodolphe Street
Durham, NC 27712
USA
 
CORRESPONDING PERSON Ron Sanyal
Sr. Manager
Regulatory Affairs
100 Rodolphe Street
Durham, NC 27712
Phone: (919) 620-2373
Fax: (919) 620-2548
 
DATE: June 5, 2003


INTENDED USE

The Vironostika HIV-1 Plus O Microelisa System is an enzyme-linked immunosorbent assay (ELISA) for the qualitative detection of antibodies to Human Immunodeficiency Virus Type 1 (HIV-1), including Group O, in human specimens collected as serum, plasma, or dried blood spots. The Vironostika HIV-1 Plus O Microelisa System is intended for use as an aid in diagnosis of infection with HIV-1. It is not intended for use in screening blood donors.

  1. INTRODUCTION

    Published data indicate a strong correlation between the acquired immunodeficiency syndrome (AIDS) and a retrovirus referred to as Human Immunodeficiency Virus (HIV). 1, 2 Currently, two HIV serotypes, designated as HIV-1 and HIV-2, have been identified based on the results of serologic and molecular studies. Both HIV serotypes have been isolated from patients with AIDS and AIDS-related complex (ARC), as well as from apparently healthy individuals at high risk for AIDS.2 Both viruses have the same morphology, lymphotropism, 3 and modes of transmission. 4 Since 1984, reports have indicated that HIV-1 can be isolated from a variety of tissues and body fluids of infected individuals. 2 , 5 In 1990, a more divergent strain of HIV-1, which is known as Group O HIV-1, was isolated and characterized. 6 Antibodies specific for group O HIV-1 are difficult to be detected with some HIV antibody detection systems unless these systems use whole viral lysate and/or contain group O specific epitopes as antigens. 7 ,8 In addition, an increasing number of variants have been identified with HIV-1 serotype, some of which have arisen from genetic recombinations within a host having infection with multiple types of HIV-1. Such variants may be more difficult to be detected with ELISA systems that are not based on viral lysate. 7 ,8 Worldwide distribution of HIV shows prevalence of the serotypes in different areas, with HIV-1 most widely distributed and Group O appearing primarily in West Central Africa.

    Following infection with HIV, an individual rapidly (e.g. within 4 weeks) develops antibodies to viral proteins, a process known as seroconversion. After seroconversion, HIV specific antibodies can be readily detected in the blood specimen. A majority of patients who exhibit symptoms of AIDS or ARC have HIV specific antibodies in their blood. In addition, a significant proportion of apparently healthy individuals at increased risk for AIDS also contain HIV specific antibodies in their blood specimens. Due to close relation of HIV-1 and HIV-2, proteins of the two viruses, especially the core and polymerase proteins, result in serologic cross-reactivity. 3

    The Vironostika HIV-1 Plus O Microelisa System assay was designed to be highly sensitive for a spectrum of HIV serotypes, including Group O virus. As a result, nonspecific reactions may occasionally be seen in specimens from people who have prior pregnancy, blood transfusion, or exposure to human cells or media containing cultured HIV antigen. 9 Because of these and other potential nonspecific reactions, specimens reactive with the Vironostika HIV-1 Plus O Microelisa System assay should be confirmed with a confirmatory test, e.g., Western Blot testing.

    Reactive specimens upon initial testing with the Vironostika HIV-1 Plus O Microelisa System assay should be re-tested in duplicate. Reactivity in either or both of the duplicate tests indicates a potential for the presence of HIV-specific antibody. In individuals at increased risk of infection, such as homosexual men, hemophiliacs, or intravenous drug users, repeatedly reactive specimens are usually found to contain antibodies to HIV by additional, more specific tests. However, when the ELISA is used to screen populations with a low prevalence of HIV infections, nonspecific reactions may be more common than specific reaction. Information about prevalence of HIV infections in persons in various categories of risk, as well as clinical and public health guidelines, are available in each CDC publication of Morbidity and Morality Weekly Reports. Although information about the degree of risk for HIV-1 infection and the degree of reactivity of the serum are of value in interpreting the test, a diagnosis should not be based only on this information. Therefore, it is appropriate to investigate repeatedly reactive specimens by additional, more specific tests, such as Western Blot, immunofluorescence, radioimmunoprecipitation, viral antigen based immunoassays, peptide ELISAs, or nucleic acid amplification assays.

  2. OVERVIEW OF THE DEVICE AND ASSAY PRINCIPAL

    The device is manufactured as a test kit, which is designed for use in clinical laboratories or other equivalent entities. The assay uses a convention, microwell plate-based ELISA format. Briefly, the anti-HIV antibodies in human specimens are captured onto a solid based (microwell plate wells) using HIV specific antigens coated on microwells. After washing to remove unbound antibodies, the bound antibodies are detected by a secondary antibody, goat anti-human immunoglobulin that is conjugated with horseradish peroxidase (HRP). HRP converts ABTS (2, 2’-azino-di-[3-ethylbenzthiazoline-6-sulfonate]) substrate to a physical green color. The intensity of the color, which can be measured with a microwell plate reader, is indicative of the presence, and relative amounts, of anti-HIV antibodies in the specimens. The determination of reactivity (positively) of the specimen is based on a cut off value that takes into account the measurements of negative controls and an adjustment factor. The adjustment factor was based on ROC analysis of pre-clinical testing results for nearly 15,000 non-reactive specimens from blood donors and many reactive specimens. Because the solid phase antigens for antibody binding consists of total HIV-1 viral lysate, a purified HIV-1 envelope protein and HIV-1 Group O specific peptide, this test is highly sensitive and specific for antibodies against the entire spectrum of HIV-1 viruses, including group O.

    This test is compatible with three types of specimens; serum, plasma and dried blood spots.

  3. MANUFACTURING AND CONTROL

    Manufacturing

    The device is manufactured by bioMérieux, Inc. under conditions that meet Quality System regulations. The manufactured components of the tests include, antigen-coated microwell plates, enzyme-antibody conjugates, buffers, positive controls, negative calibrator, and other solutions.

    Raw materials are subjected to appropriate quality control evaluations prior to their acceptance for use in manufacturing. The quality of the product is controlled in multiple stages, e.g., during manufacturing (in-process controls) and after completion of component manufacturing (release control). Specifications for these in-process controls and release controls were established and validated. The final kit lot is assembled with various component lots and subjected to a final kit performance test. Only when all testing meets pre-determined specifications are the final kit lots released for marketing.

    Stability

    A stability of kit components was established based on real time stability studies. Current data supports 15-month stability dating for finished kit lots.

    Establishment

    The product is manufactured in dedicated facilities, where the water and air systems are monitored. There is a testing laboratory in the manufacturing area, where most in-process testing is performed. In addition, a testing laboratory is supervised by the Quality Control Group and is used for release testing. Finished and assembled kits are stored under appropriate conditions in a warehouse for shipping.

    Environment

    All hazardous materials or waste are managed in accordance with applicable local, state and Federal Regulations.

    The test kit contains HIV-1 positive controls, which are appropriately inactivated. However, the users are advised to treat these components as if they were infectious. Appropriate precautionary statements are included in the labeling and package insert of the product.

  4. PERFORMANCE CHARACTERISTICS OF THE TEST

    Reproducibility

    Replicates of HIV-1 antibody positive serum, plasma, and dried blood spot specimens with various degrees of reactivity, negative specimens, and kit controls were tested at multiple sites (n=3), using multiple kit lots (n=3) and multiple technicians (n=3) on multiple days (n=4). Total, inter-assay, and intra-assay precision is reported in table 1 below. The total coefficient of variation (CV) for specimens 1-4 ranged from 11.0 to 22.4%.

    Table 1: Assay Reproducibility
        Total Inter-assay Intra-assay
    Specimen Type ID N Mean SD CV (%) SD CV (%) SD CV (%)
    Serum or Plasma 1
    2
    3
    4
    NC
    PC 1
    PC 0
    72
    72
    72
    72
    108
    36
    36
    2.78
    2.67
    5.48
    4.77
    0.33
    4.78
    4.04
    0.561
    0.549
    0.602
    0.797
    0.031
    0.732
    0.883
    20.2
    20.6
    11.0
    16.7
    9.4
    15.3
    21.8
    0.533
    0.472
    0.538
    0.711
    19.2
    17.7
    9.8
    14.9
    0.185
    0.287
    0.278
    0.369
    6.7
    10.8
    5.1
    7.7
    Dried Blood Spots 1
    2
    3
    4
    NC
    PC 1
    PC 0
    72
    72
    72
    72
    108
    36
    36
    1.57
    1.86
    3.70
    3.60
    0.34
    5.38
    4.25
    0.272
    0.416
    0.782
    0.676
    0.036
    0.502
    0.674
    17.3
    22.4
    21.1
    18.8
    10.7
    9.3
    15.9
    0.240
    0.347
    0.678
    0.611
    15.3
    18.7
    18.3
    16.9
    0.131
    0.232
    0.398
    0.299
    8.4
    12.5
    10.8
    8.3

    ID Specimen Identification
    N Number of Replicates
    Mean Mean Signal to Cutoff Ratio (SCR)
    SD Standard Deviation of SCR
    CV Coefficient of Variation of SCR
    NC Negative Control
    PC 1 HIV-1 Positive Control
    PC O HIV-1 Group O Positive Control

    Specificity

    The specificity of the Vironostika HIV-1 Plus O Microelisa System was assessed by testing 6,032 serum/plasma specimens and 3,031 dried blood spot specimens collected from three low risk populations, including voluntary blood donors, insurance applicants and Planned Parenthood clinic patients. The licensed Vironostika HIV-1 Microelisa System was used for comparison. All specimens that were repeatedly reactive with either test were further tested with an FDA licensed Western blot assay.

    Of the 6,032 serum/plasma specimens tested, thirteen (13) were repeatedly reactive with the Vironostika HIV-1 Plus O Microelisa System and subsequently confirmed HIV-1 antibody positive with a Western blot assay. In contrast, only 12 of the 13 positive specimens were reactive with the comparative test. As summarized in table 2, the specificity for the Vironostika HIV-1 Plus O Microelisa System in this study was estimated to be 100% (6,019/6,019), with a 95% confidence interval of 99.94 - 100%.

    Of the 3,031 dried blood spot specimens, thirteen (13) were repeatedly reactive with the Vironostika HIV-1 Plus O Microelisa System. These repeatedly reactive specimens matched those of serum specimens, which were confirmed positive with a Western blot assay. The comparative test again detected only 12 of the 13 positive specimens. The specificity for the Vironostika HIV-1 Plus O Microelisa System was estimated in this study to be 100% (3,018/3018), with a 95% confidence interval of 99.88 - 100% for dried blood spots.

    Table 2: Estimated Specificity in Low-Risk Populations
        Number
    tested
    Non-
    reactive
    Initially
    Reactive
    Repeatedly
    Reactive
    Western
    Blot
    Positive
    Serum or
    Plasma
    Population 1 1,500 1,500 0 0 N/A
    Population 2 3,012 3,012 0 0 N/A
    Population 3 1,520 1,506 14 13 13
    Total 6,032 6,018 14 13 13
    Dried
    Blood
    Spot
    Population 1 0 N/A N/A N/A N/A
    Population 2 1,511 1,511 0 0 N/A
    Population 3 1,520 1,506 14 13 13
    Total 3,031 3,017 14 13 13

    N/A     Not applicable

    The estimation of specificity is as follows:

      (Number screened – Number repeatedly reactive)
      (Number screened – Number Western blot test positive)

    Sensitivity

    The clinical sensitivity of the Vironostika HIV-1 Plus O Microelisa System was evaluated by testing matched serum/plasma specimens and dried blood spot specimens collected from 1,010 HIV-1 infected individuals with various CD4+ counts. These specimens were collected from six sites. Of the 1,010 dried blood spot specimens, 904 (90%) were collected directly as dried blood spots while 106 (10%) were collected with an indirect technique (100 µl of anticoagulated blood spotted onto filter paper).

    As summarized in table 3, all serum/plasma specimens and dried blood spot specimens were repeatedly reactive with the Vironostika HIV-1 Plus O Microelisa System. Therefore, the sensitivity for both specimen types in this study was 100% (95% CI: 99.64-100%).

    Table 3: Estimation of Clinical Sensitivity
    Specimen
    Type
    CD4+
    Stratum
    Number of
    specimens
    Number of
    Initially
    Reactive
    Number of
    Repeatedly
    Reactive
    Serum or
    Plasma
    <200
    200-499
    >499
    Total
    250
    385
    375
    1,010
    250
    385
    375
    1,010
    250
    385
    375
    1,010
    Dried Blood
    Spots
    <200
    200-499
    >499
    Total
    250
    385
    375
    1,010
    250
    385
    375
    1,010
    250
    385
    375
    1,010

    High-risk populations

    To assess the performance of the test with specimens collected from high-risk populations, fifteen hundred and fourteen (1,514) specimens were collected from four high-risk populations, which included prison inmates, STD (sexually transmitted diseases) clinic patients, inner city hospital emergency room patients, and HIV-1 outreach clinic patients. In addition, seven hundred and fifty (750) dried blood spot specimens were also collected from two of the study populations.

    Serum/plasma specimens were tested with both the licensed Vironostika HIV-1 Microelisa System for comparison (comparative test) and the Vironostika HIV-1 Plus O Microelisa System. If repeatedly reactive with either or both tests, the specimens were further tested with a Western blot assay for confirmation. Dried blood spot specimens were tested only with the Vironostika HIV-1 Plus O. Table 4 lists the test results for the Vironostika HIV-1 Plus O Microelisa System.

    Table 4: High-risk Populations
    Specimen Type Population Number of
    specimens
    Number of
    Initially
    Reactive
    Number of
    Repeatedly
    Reactive
    Western Blot
    Positive
    Serum or
    Plasma
    1
    2
    3
    4
    Total
    251
    513
    500
    250
    1,514
    16
    13
    73
    28
    130
    14
    13
    68
    27
    122
    8
    13
    68
    27
    116*
    Dried Blood
    Spots
    1
    2
    3
    4
    Total
    0
    0
    500
    250
    750
    N/A
    N/A
    68
    27
    95
    N/A
    N/A
    68
    27
    95
    N/A
    N/A
    68
    27
    95

    *Three repeatedly reactive specimens in population 1 were indeterminate with the Western blot assay due to the presence of only a gp160, a gp120 or a 70 kDa band. The other 3 specimens were not tested by Western blot.

    N/A     Not applicable

    Table 5 shows a summary of the agreement of test results obtained with the Vironostika HIV-1 Plus O and the licensed test with specimens from high risk populations. The 6 specimens that were repeatedly reactive (RR) with the Vironostika HIV-1 Plus O assay but non-reactive (NR) with the licensed test were considered to be false positive on the Vironostika HIV-1 Plus O assay. Therefore, the specificity of the Vironostika HIV-1 Plus O assay in this study of high risk populations was calculated to be 1392/1398 = 99.57% (95% CI = 99.07% – 99.84%).

    Table 5: Comparison of the Vironostika HIV-1 Plus O Assay with the licensed Vironostika HIV-1 Microelisa System in testing Specimens from High Risk Populations
      Licensed Test  
    Vironostika HIV-1 Plus O
      RR NR Total
    RR 116 6* 122
    NR 0 1392 1392
    Total 116 1398 1514

    *Western blot results were indeterminate for 3 of these specimens. The other 3 specimens were not tested by Western blot.

    Seroconversion Panel Testing

    Twelve (12) seroconversion panels were tested in triplicate with the Vironostika HIV-1 Plus O Microelisa System and the licensed Vironostika HIV-1 Microelisa System. Due to insufficient amounts of samples, only 10 of the 12 panels were also tested as DBS specimens.

    For serum specimens, the Vironostika HIV-1 Plus O Microelisa System detects the reactivity earlier than the comparative test in all 12 panels.

    Table 6: Seroconversion Panel Testing
    Panel ID Sample
    Collection
    Days
    First Reactive Bleed (Days from the First Bleed)
    Serum DBS1
    Vironostika
    HIV-1 Plus O
    System
    Comparative
    Test2
    Vironostika
    HIV-1 Plus O
    System
    Comparative Test2
    924 8, 10, 26, 33,
    35, 40
    33 40 33 NR
    927 0, 28, 33, 35,
    40
    33 40 35 40
    931 9, 15, 28, 33,
    35, 42
    28 33 28 33
    932 0, 3, 13, 27,
    34, 50, 78,
    163, 194
    34 NR3 78 NR
    940 0, 7, 11, 15,
    18, 22, 25, 29
    15 22 18 25
    071 1, 3, 17, 22, 28 17 22 22 28
    111 1, 2, 8, 16, 20,
    22, 27
    8 16 NT4 NT
    241 1, 7, 9, 15, 17,
    22, 24
    15 22 17 24
    321 1, 8, 12, 15, 21 15 21 15 21
    341 1, 7, 10, 21,
    23, 28
    21 28 28 28
    351 1, 8, 11, 15 15 NR NT NT
    361 1, 3, 9, 11, 16,
    18
    18 NR NR NR

    1Dried Blood Spot specimens
    2The licensed Vironostika HIV-1 Microelisa System was used
    3None of the specimens in this panel was reactive
    4Not tested due to limited sample volumes

    Dilution Panel Testing

    Ten (10) serum specimens representing various HIV-1 group M clades and HIV-1 group O were used to prepare 10 serially diluted panels, which were then tested with the Vironostika HIV-1 Plus O Microelisa System and the licensed Vironostika HIV-1 Microelisa System. Each specimen was tested in duplicate with each of the three kit lots. The first dilutions that gave one or more non-reactive test result in each panel are presented in table 7. Highly diluted serum samples remained reactive with the test for all panels including the two HIV-1 group O panels. The Vironostika HIV-1 Plus O Microelisa System exhibited higher analytical sensitivity with the dilutional panels for both HIV-1 group M clades and HIV-1 group O specimens compared to the comparative test.

    Table 7: First dilutions with non-reactive test results for each dilution series
    Sample ID Clade Type
    Serum
    Vironostika HIV-1
    Plus O System
    Comparative Test1
    5805 HIV-1 Clade B 1:1,920 1:240
    H629 HIV-1 Clade B 1:32,000 1:8,000
    MD-O HIV-1 Group O 1:25,600 1:400
    302-1 HIV-1 Group O 1:1,600 NR2
    301-42 HIV-1 Clade A 1:12,800 1:1,600
    302-18 HIV-1 Clade C 1:6,000 1:1,500
    301-24 HIV-1 Clade D 1:48,000 1:3,000
    302-23 HIV-1 Clade E 1:24,000 1:1,500
    302-28 HIV-1 Clade F 1:12,800 1:1,600
    302-17 HIV-1 Clade D 1:4,000 1:250
    1The licensed Vironostika HIV-1 Microelisa System
    2Non-reactive

    Detection of HIV-1 Group M Clades

    Seventy-two (72) specimens representing infections with various clades of HIV-1 group M viruses were tested in duplicate with the Vironostika HIV-1 Plus O Microelisa system. Since there were limited amounts for most specimens, all specimens were diluted by 100 to 10,000 times prior to testing. Table 8 shows the test results for serum/plasma specimens. All specimens were repeatedly reactive with the assay, despite the dilution factors.

    Table 8: Detection of HIV-1 Group M Clades
    Clade Number of
    Specimens
    Sample Dilution
    Factor
    Number of
    Repeatedly
    Reactive
    Number of Non-
    reactive
    A 10 100 to 10,000 10 0
    B 12 100 to 10,000 12 0
    B/D 1 100 1 0
    C 10 100 to 10,000 10 0
    C/E 1 1,000 1 0
    D 10 100 to 10,000 10 0
    E 7 100 to 5,000 7 0
    E/A 3 1,000 3 0
    E/C 1 10,000 1 0
    E/F 1 100 1 0
    F 10 100 to 10,000 10 0
    G 4 1,000 to 5,000 4 0
    H 2 1,000 2 0
    Total 72   72 0

    Detection of HIV-1 Group O Specimens

    Archived serum specimens from eleven (11) HIV-1 Group O infected individuals were tested after dilution. These specimens were tested in duplicate with both the Vironostika HIV-1 Plus O Microelisa System and the licensed Vironostika HIV-1 Microelisa System. As shown in table 9, all eleven (11) specimens were repeatedly reactive with the Vironostika HIV-1 Plus O Microelisa System, while only 7 of the 11 were reactive with the comparative test. For all 11 specimens, the Signal to Cutoff Ratio (SCRs) were significantly higher with the Vironostika HIV-1 Plus O as compared to the licensed Vironostika HIV-1 based on the Wilcoxon Signed Rank test.

    Table 9: Detection of HIV-1 Group O Specimens
    Specimen ID Sample Dilution
    Vironostika HIV-1 Plus O
    System
    Comparative Test1
    Mean SCR2 Mean SCR
    1 1:100 6.1 2.0
    2 1:50 4.0 0.4
    3 1:50 7.4 1.6
    4 1:50 5.6 1.1
    5 1:50 7.7 2.0
    6 1:50 7.7 7.2
    7 1:50 5.3 0.5
    8 1:50 7.6 2.2
    9 1:50 5.9 0.4
    10 1:50 3.9 0.4
    11 1:50 7.6 4.5
    Total Repeatedly Reactive 11/11 7/11

    1The licensed Vironostika HIV-1 Microelisa System
    2SCR = Signal to Cutoff Ratio

    Detection of HIV-2 Positive Specimens

    Twenty (20) HIV-2 positive serum/plasma specimens were diluted and tested in duplicate with the Vironostika HIV-1 Plus O Microelisa System. All HIV-2 specimens were repeatedly reactive with the Vironostika HIV-1 Plus O Microelisa System. The test results are listed below in table 10.

    Table 10: Detection of HIV-2 Specimens
    Specimen ID Sample Dilution Mean SCR*
    1 1:10 3.3
    2 1:10 5.8
    3 1:500 1.5
    4 1:10 4.3
    5 1:50 1.7
    6 1:10 5.5
    7 1:10 2.5
    8 1:10 5.0
    9 1:100 3.7
    10 1:1,000 1.8
    11 1:200 1.3
    12 1:200 1.4
    13 1:10 1.9
    14 1:50 1.3
    15 1:1,000 4.9
    16 1:1,000 3.6
    17 1:50 1.7
    18 1:1,000 2.7
    19 1:10 2.0
    20 1:10 1.8

    *Specimens with SCR equal to or greater than 1.0 are considered reactive with the test.

    Reactivity with Potentially Interfering Substances or Medical Conditions Serum or plasma specimens (S/P)

    Samples were collected from individuals with medical conditions that may cause nonspecific assay reactivity. These specimens were tested using the Vironostika HIV-1 Plus O Microelisa System. As shown in table 11, all but one specimens (184/185) were non reactive with the test. The one specimen weakly reactive with the test was from an individual with elevated bilirubin. Further analysis of this specimen with a Western blot assay showed the presence of antibodies weakly reactive with gp160. Therefore, elevated bilirubin was unlikely the cause for the reactivity of the specimen. Rather, the presence of nonspecific antibody in the sample contributed to the weak reactivity.

    In a second study, the 184 non-reactive samples were spiked with a small volume of HIV-1 positive sample and tested with the system. All specimens were reactive with the Vironostika HIV-1 Plus O Microelisa System. The medical conditions listed in table 11 did not affect the reactivity of specimen spiked with HIV-1 seropositive sample.

    Dried blood spot specimens (DBS)

    A similar study was also performed using dried blood spot specimens. As shown in table 11, all 184 specimens were non-reactive with the Vironostika HIV-1 Plus O Microelisa System. When spiked with a small volume of HIV-1 seropositive sample, all 184 specimens were reactive with the system. No interference was observed with dried blood spot specimens.

    Table 11: Reactivity of Specimens from Individuals with Potentially Interfering Substances
    or with Medical Conditions
    Specimen type Number of
    specimens
    Neat Specimens Spiked Specimens
    No. of
    Reactive
    No. of
    non-reactive
    No. of
    Reactive
    No. of non-
    reactive
      S/P DBS S/P DBS S/P DBS S/P DBS S/P DBS
     
    Antinuclear antibody positive
    CMV antibody positive
    EBV antibody positive
    Rubella antibody positive
    Elevated bilirubin1
    Hemolysed specimens
    HSV-1 or HSV-2 antibody positive
    HTLV-I or HTLV-II antibody positive
    Lipemic2
    Multiple transfusion
    Multiparous females
    Rhematoid factor positive
    SLE positive
    Syphilis antibody positive
    Toxaplasmosis gondii positive
    HBV antigen positive
    HCV antibody positive
    Hypergammaglobulinemia
    Influenza vaccinated

    Total
     
    10
    10
    10
    9
    10
    10
    10
    10
    10
    10
    10
    10
    10
    10
    7
    10
    10
    9
    10

    185

     
    10
    10
    10
    9
    10
    10
    10
    10
    10
    10
    10
    10
    10
    10
    7
    10
    10
    8
    10

    184

     
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0

    1

     
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0

    0

     
    10
    10
    10
    9
    9
    10
    10
    10
    10
    10
    10
    10
    10
    10
    7
    10
    10
    9
    10

    184

     
    10
    10
    10
    9
    10
    10
    10
    10
    10
    10
    10
    10
    10
    10
    7
    10
    10
    8
    10

    184

     
    10
    10
    10
    9
    9
    10
    10
    10
    10
    10
    10
    10
    10
    10
    7
    10
    10
    9
    10

    184

     
    10
    10
    10
    9
    9
    10
    10
    10
    10
    10
    10
    10
    10
    10
    7
    10
    10
    8
    10

    184

     
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0

    0

     
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0

    0

    1 >6.3 mg/dL
    2 >980 mg/dL

  5. POTENTIAL ADVERSE EFFECT OF THE DEVICE

    As an in vitro diagnostic test, the device has little direct adverse effect on the individuals for whom the samples are tested with the Vironostika HIV-1 Plus O Microelisa System. However, a false negative result will likely result in delayed medical attention to an infected individual. A false positive result may result in unnecessary psychological impact on an individual. Given the excellent sensitivity and specificity demonstrated during the clinical trials, a false negative or reactive result and its associated adverse effect would be a highly unlikely event.

  6. CONCLUSIONS

    The Vironostika HIV-1 Plus O Microelisa System is a safe and effective assay for diagnostic detection of antibodies to HIV-1, including Group O, in human serum, plasma or dried blood spot specimens.

  7. REFERENCES

    1. Hardy AM, Allen, JR, Morgan WM, et al. The Incidence Rate of Acquired Immunodeficiency Syndrome in Selected Populations. JAMA 1985:253(2):215-20.

    2. Gallo RC, Salahuddin SZ, Popovic M, et al. Frequent Detection and Isolation of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and at Risk for AIDS. Science 1984;224:500-3.

    3. Brun-Vezinet F, Katlama C, Roulot D, et al. Lymphadenopathy associated virus type 2 in AIDS and AIDS-related complex. Lancet 1987; 1:128-32.

    4. Quinn TC, Zacarias FRK, St. John RK, et al. AIDS in the Americans: an emerging public health crisis. New Engl. J. Med. 1989; 320:1005-7.

    5. Markham P, Salahuddin SZ, et al., Advances in the isolation of HTLV-III from patients with AIDS and AIDS-related complex and from donors at risk. Cancer Res. (Suppl.) 1985; 45:4588-91.

    6. De Leys R, Vanderborght B, Vanden HaeseVelde M, et al. Isolation and partial characterization of an unusual human immunodeficiency retrovirus from two persons of West-Central African origin. J. Virol. 1990; 64:1207-16.

    7. Loussert-Ajaka I, Ly TD, Chaix ML, et al. HIV-1/HIV-2 seronegativity in HIV-1 subtype O infected patients. The Lancet 1994; 343: 1393-4.

    8. Schable C, Zekeng C, Pau CP, et al. Sensitivity of United States HIV antibody tests for detection of HIV-1 Group O infections. The Lancet 1994; 344:1333-4.

    9. Kuhnl P, Seidl S, Holzberger G: HLA DR4 Antibodies Cause Positive HTLV-III Antibody Elisa Results. The Lancent 1985; 1222-3.g

 

 
horizonal rule