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.
- 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.
- 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.
- 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.
- 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< td>
| 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
- 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.
- 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.
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