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HIV ASSAYS: OPERATIONAL CHARACTERISTICS (PHASE I)

REPORT 12 SIMPLE/RAPID TESTS WHOLE BLOOD SPECIMENS

World Health Organization


REPORT 12 SIMPLE/RAPID TESTS WHOLE BLOOD SPECIMEN

World Health Organization Department of Essential Health Technologies

WHO Library Cataloguing-in-Publication Data

World Health Organization.

HIV assays : operational characteristics (Phase I). Report 12: simple/rapid tests, whole blood specimens.

1.AIDS serodiagnosis - methods 2.Blood - virology 3.Reagent kits, Diagnostic-utilization 4.Clinical trials, Phase I 5.HIV seropositivity - diagnosis I.Title.

ISBN 92 4 159235 4 (NLM classification: WC 503.1)

This publication is a reprint of material originally distributed as WHO/BCT/02.07

© World Health Organization 2002

All rights reserved. Publications of the World Health Organization can be obtained from Marketing and Dissemination, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel: +41 22 791 2476; fax: +41 22 791 4857; email: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to Marketing and Dissemination, at the above address (fax: +41 22 791 4806; email: [email protected]). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.

WHO, UNAIDS, and the Institute of Tropical Medicine, Antwerp, Belgium, do not warrant or represent that the evaluations conducted with the HIV test kits referred to in this document are accurate, complete and/or error-free. WHO, UNAIDS and the Institute of Tropical Medicine disclaim all responsibility for any use made of the data contained herein, and shall not be liable for any damages incurred as a result of its use. This document must not be used in conjunction with commercial or promotional purposes.

Printed in France

_____________________________________________________________________

Contact: Dr G. Vercauteren, Essential Health Technologies - WHO - 20, Avenue Appia - 1211 Geneva 27- Switzerland

This document is available on the internet at: www.who.int/eht/


REPORT 12

SIMPLE/RAPID TESTS

WHOLE BLOOD SPECIMENS

Table of Contents

1. Introduction 1

2. Background information 1

3. Laboratory aspects of HIV testing 3 3.1 A brief overview 3 3.2 Quality assurance 3 3.3 Safety 4

4. Materials and Methods 4 4.1 Assays (test kits) evaluated 4 4.2 Evaluation panel 8 4.3 Laboratory testing 8 4.4 Data analysis 9

4.4.1 Sensitivity, specificity, confidence limits and predictive values of HIV tests 9 4.4.2 Inter-reader variability 10 4.4.3 Sensitivity in seroconversion panels 10 4.4.4 Additional analyses 11

5. Assay evaluations 11 Table 1: General characteristics and operational aspects 13 Table 2: Comparison of whole blood anti-HIV assays with reference tests 14 Table 3: Detailed operational aspects 15 Table 4a: Technician's appraisal of the test kits 17 Table 4b: Calculation of ease of performance 18 Table 5: Suitability for use in small laboratories 19 Table 6: Performance on seroconversion panels 20 Figure 1: Relative performance on seroconversion panels 22 Explanatory notes for Tables 1-6 and Figure 1 23

6. Annexes 25 Annex 1: Algorithm for characterization of the WHO HIV panel 25 Annex 2: List of assay manufacturers'/distributors' addresses 26

7. Additional reading 26

8. Acknowledgements 26

9. Note 26

1 INTRODUCTION Since 1988, the World Health Organization (WHO), conscious of the need to advise Member States on the laboratory diagnosis of HIV, has been providing member states with objective assessments of the operational characteristics of commercially available HIV tests. This continuing program is carried out by the WHO Collaborating Centre at the Department of Microbiology, Institute of Tropical Medicine, Antwerp, Belgium and is coordinated by the Department of Blood Safety and Clinical Technology, WHO, Geneva in conjunction with UNAIDS. The WHO evaluation scheme provides information that is useful for decision-makers to allow them to make the most suitable choices. The assessment focuses on the operational characteristics of these assays, such as sensitivity, specificity, and positive and negative predictive values. Additional information related to incubation temperatures, shelf-life and ease of use are also provided. Report 12, dealing with the evaluation of the major operational characteristics of commercially available assays to detect antibodies to HIV in whole blood specimens, presents assessments of the following seven assays carried out between May 2000 and September 2000:

• Determine™ HIV-1/2 (Abbott Laboratories)

• InstantScreen™ Rapid HIV-1/2 Assay (GAIFAR GmbH)

• ADVANCED QUALITY™ Rapid HIV Test (InTec Products Inc.)

• MedMira Rapid HIV Test (MedMira Laboratories Inc.)

• First Response™ HIV-1/HIV-2 WB (PMC Medical Pty. Ltd)

• CAPILLUS™ HIV-1/HIV-2 (Trinity Biotech PLC)

• Uni-Gold™ HIV (Trinity Biotech PLC) This report provides data of phase I of the WHO coordinated evaluation of seven anti-HIV simple/rapid (S/R) test kits using whole blood specimens. Phase II, is planned for 2002, and will include field testing. Copies of this report are available on request from the Blood Safety Team, Department of Blood Safety and Clinical Technology, World Health Organization, 1211 Geneva 27, Switzerland. The report is also available on the BCT section of the WHO website www.who.int/bct 2. BACKGROUND In the last few years there have been a number of improvements of S/R tests for the detection of HIV antibodies (anti-HIV). One important advancement has been the development of assays that detect HIV antibodies in human whole blood, whereas previously samples of serum or plasma were required. Further refinements have meant that the sensitivity and specificity of S/R tests has increased. These developments may be of particular use in voluntary counselling and testing (VCT) and/or prevention of mother-to-child transmission (PMTCT) initiatives, as it is recognised that an individual’s knowledge of their HIV status is the first step in halting the spread of the disease and for seeking appropriate clinical care. For such initiatives to be effective,

whether carried out in central laboratories or small health centres, it is necessary to identify the most appropriate assay for their particular circumstances. The need for reliable tests that can be used in situations with limited laboratory facilities continues to drive the development of S/R tests for anti-HIV in recent years. Transport to rural areas is less of a logistical problem when only the S/R tests themselves are required and there is no necessity for the delivery of numerous bulky items of equipment, as would be required for other test formats, such as ELISAs. These tests are simple in that they need little or no equipment, have few manipulation steps, can be read visually and are suitable for use on single or low numbers of specimens. Such tests can be carried out by less experienced staff, nonetheless the personnel should have a minimum of training with regard to the operation and interpretation of results, have undergone safety training and operate within a quality assurance programme. The tests are also rapid in that the time required to complete the assay is short, frequently less than 15 minutes. The development of S/R tests that can detect HIV antibodies in whole blood in addition to serum and plasma has allowed the use of these assays in situations where the necessity for equipment such as a centrifuge is impracticable, eg rural health clinics or voluntary counselling and testing services (VCT).. In such settings it is possible to carry out the testing immediately after the blood specimen is taken, thus reducing further the waiting time for results. The possibility of error in specimen labelling is also reduced as the original specimen is used and there is no necessity to remove an aliquot of the serum into a new vial. Nonetheless, clerical error may still occur if the system is not well organised and a quality system should be in place. A disadvantage of whole blood specimens is that they deteriorate on storage and therefore cannot be used for further testing at a later date, in which case a serum specimen would be required. Whether the whole blood sample is a venous sample or obtained by fingerprick, it is essential that the site from which the sample is taken should be covered to reduce risk of infection and that proper waste disposal facilities for sharps are available. The majority of S/R tests can be carried out at ambient temperature and often the kits may be stored at temperatures between 2°C and 30°C, some even up to 45°C. In most cases the kits contain the reagents ready-for-use which, combined with the ease of use and incorporation of an internal control, helps to reduce technical errors. The characteristics of such assays lend themselves readily for use in resource-poor settings where the infrastructure and human resources do not necessarily support the use of ELISA techniques and also in situations where it is necessary to give the patient the result immediately. Although the cost per test of S/R tests may be higher than that for ELISAs tests, when the latter are used to test small numbers at a time the cost can become greater. Indeed, when the above factors are taken into account it can be seen that the results obtained in such settings may be more reliable when S/R tests as opposed to ELISA techniques are employed and the use of S/R tests to be the optimal choice. There are situations where S/R tests may prove more appropriate for use in what would normally be considered those more suitable for ELISAs, eg blood donor screening, especially when using S/R tests of high quality. As an example, in an emergency situation where the time required for an ELISA test would be too great, the speed of use

for a rapid test may make it more favourable to an ELISA test. In the same situation, the higher comparative cost of carrying out a single ELISA test compared with a single S/R test may not be acceptable. Thus the flexibility and speed of reliable S/R tests can make them very cost-effective, and possibly preferable, in many situations. 3. LABORATORY ASPECTS OF HIV TESTING

3.1 A brief overview

The diagnosis of HIV infection is usually made on the basis of the detection of antibodies to HIV. Serological tests for detecting antibodies to HIV are generally classified as screening tests (sometimes referred to as initial tests) or confirmatory tests (sometimes referred to as supplemental tests). Initial tests provide the presumptive identification of antibody-positive specimens, and supplemental tests are used to confirm whether specimens found reactive with a particular screening test contain antibodies specific to HIV. When a single screening assay is used for testing in a population with a very low prevalence of HIV infection, the probability that a person is infected when a positive test result is obtained (i.e., the positive predictive value) is very low, since the majority of people with positive results are not infected. This problem occurs even when a test with high specificity is used. Accuracy can be improved if a second supplemental test is used to retest all those samples found positive by the first test. Those found negative by the test are considered negative for antibodies to HIV.

Confirmation of the results obtained with alternative specimens may pose some challenges. For serum/plasma specimens the most commonly used confirmatory test was the Western blot (WB), however its use has proven to be very expensive and can, under some conditions, produce a relatively large number of indeterminate results. Similar assays, generically called line immunoassays (LIAs), based on recombinant and/or synthetic peptides capable of detecting antibodies to specific HIV 1 and/or HIV 2 proteins, have been developed, eg INNOLIA and Pepti-LAV. In general these assays produce fewer indeterminate results as compared with WB but are equally expensive. Studies have shown that combinations of ELISAs or S/R assays can provide results as reliable as the WB at a much lower cost. WHO and UNAIDS therefore recommend that countries consider testing strategies that use ELISAs and S/R assays rather than ELISA/WB for HIV antibody detection.

3.2 Quality assurance

All laboratories carrying out HIV tests, should have a well-functioning quality assurance programme. It is most important that quality assurance procedures be stringently applied so as to maximize the accuracy of the laboratory results. Procedures for detecting both (technical) laboratory and clerical errors must be included in all protocols, for example, procedures that guarantee that the correct results are communicated to the individuals seeking to know their HIV status. External Quality

Assessment Schemes (EQAS) are available for HIV serology and it is recommended that laboratories participate in an EQAS, wherever possible, at least once a year to monitor their performance. 3.3 Safety The testing of whole blood specimens should be performed in such a manner as to minimize occupational risk, in the same way as that for serum and plasma specimens. Guidelines for good laboratory practice have been developed that, if followed, will ensure safety and keep laboratory accidents to a minimum. For further details see the Laboratory Biosafety Manual, second edition, World Health Organization, Geneva, 1993 (ISBN 92 4 154450 3) and the Communicable Diseases Surveillance and Response section of the WHO website, www.who.int/emc , where information on laboratory biosafety and transport of infectious substances may be found. 4 MATERIALS AND METHODS 4.1 Assays (test kits) evaluated

Test kits for these assessments were kindly provided to WHO free of charge by each of the manufacturers of the assays under evaluation. The manufacturers were invited to visit the site at which the assessments were to be conducted in order to provide any required training and to ensure that the assays were performed correctly by the laboratory staff carrying out the evaluation of their assays. All of the test kits can be used with serum serum/plasma specimens, however in this evaluation the tests were carried out on a WHO panel of whole blood specimens and on eight commercial serum seroconversion panels (see section 3.2). Determine™ HIV-1/2 (Abbott Laboratories, Il, USA) Product code 7D23-33 An in-vitro immunochromatographic (lateral flow) test for the qualitative detection of antibodies to HIV 1 and HIV 2 in human serum, plasma and whole blood. For testing whole blood specimens, an extra step is required, ie to add chase buffer after the addition of the blood sample.

InstantScreen™ Rapid HIV-1/2 Assay (GAIFAR GmbH, Potsdam, Germany) Product code not available An in-vitro immunochromatographic (lateral flow) test for the qualitative detection of antibodies to HIV 1 and HIV 2 in human serum, plasma and whole blood. The testing procedure is identical for all three specimen types. Two versions of the assay were tested in the evaluation, InstantScreen™ Rapid HIV-1/2 assay Generation 1 and InstantScreen™ Rapid HIV-1/2 assay Generation 2. The assays differ in formulation, binding procedure and concentrations of the antigen components of the assay. The Generation 1 assay has been replaced by the Generation 2 assay. (Image of the test device is not available) ADVANCED QUALITY™ Rapid HIV Test (InTec Products Inc., Xiamen, China) Product code ITP02002-TC40 An enhanced rapid immunochromatographic (lateral flow) test for the qualitative detection of antibodies to HIV 1 and HIV 2 in human serum, plasma and whole blood. For serum and plasma samples the sample diluent is added immediately after the specimen whereas for whole blood specimens it is necessary to wait approximately 20 seconds before addition of the sample diluent.

MedMira Rapid HIV Test (MedMira Laboratories Inc. Toronto, Canada) Product code not available An in-vitro immunofiltration test for the qualitative detection of antibodies to HIV 1 and HIV 2 in human serum, plasma and whole blood. For serum/plasma specimens, the sample is added directly to the device membrane. For whole blood specimens the sample is added to a filter unit that is placed on the device. The filter unit is discarded after addition of sample and buffer but prior to addition of conjugate solution. Images shown are of two versions of the MedMira Rapid HIV test provided by the company. The single test dot format, version 1, was tested in the WHO whole blood panel. The 2-line format, version 2, was a later version of the assay which was used for testing with the commercial seroconversion panels. First Response™ HIV-1/HIV-2 WB (PMC Medical Pty. Ltd., Daman, India) Product code DD/138 An in-vitro immunochromatographic (lateral flow) test for the qualitative detection of antibodies to HIV 1 and HIV 2 in human serum, plasma and whole blood. 25µl of serum/plasma or 30µl whole blood is required for the assay, otherwise the testing procedure is the same for all specimen types.

Version 1 Version 2

CAPILLUS™ HIV-1/HIV-2 (Trinity Biotech PLC., Bray, Ireland) Product code 6048G A latex agglutination test for the detection of antibodies to HIV 1 and HIV 2 in human serum, plasma and whole blood. The testing procedure is the same for all three specimen types. At the time of the evaluation the manufacturer stated that the kit was validated for whole blood specimens although this was not stated in the kit insert. The kit insert has since been updated detailing the testing procedure for serum, plasma and whole blood. Uni-Gold™ HIV (Trinity Biotech PLC., Bray, Ireland) Product code 1206502 An in-vitro immunochromatographic (lateral flow) test for the qualitative detection of antibodies to HIV 1 and HIV 2 in human serum, plasma and whole blood. The testing procedure is the same for all three specimen types. Two versions of the Uni-Gold™ HIV test, one containing peptide antigen and one containing recombinant antigen, were available at the time of the evaluation. The version included in this evaluation is that which contained recombinant antigen. The Uni-Gold™ HIV peptide test is no longer in production.

4.2 Evaluation panel

Two hundred and fifty (250) whole blood samples were collected into EDTA tubes along with a matched serum sample from individuals who gave consent to be included in this trial at ITM, Antwerp, Belgium. Eighty anti-HIV positive and 170 anti-HIV negative samples were prospectively collected for this evaluation.

The composition of the panel collected is shown below.

Composition of WHO HIV whole blood and matched serum panel, Phase 1

Anti-HIV Positive

Anti-HIV Negative

Total

80 170 250

32% 68% 100%

For characterization, the matched serum samples were screened with 2 reference ELISAs, Vironostika HIV Uni-Form II plus O (Organon Teknika) and the Enzygnost Anti-HIV 1/2 Plus (Behringwerke AG). Specimens non-reactive in both assays were considered anti-HIV negative. Specimens that were initially reactive in either assay were repeated in duplicate. Specimens repeatedly reactive in either or both ELISAs were further characterised using an immunoblot, InnoLIA HIV Confirmation (Innogenetics). The algorithm for the characterization of the matched serum samples is presented in Annex 1.

In addition to the anti-HIV positive and negative samples, eight commercial serum/plasma seroconversion panels from Boston Biomedica Inc. (BBI) were tested in each of the 7 assays evaluated.

4.3 Laboratory testing

The whole blood specimens included in the WHO whole blood panel were tested immediately after collection and in accordance with each manufacturer's instructions. All assay runs were performed by one operator and visual interpretations of the results were made independently by three technicians. Whole blood specimens in the WHO HIV panel that gave initial results discordant from the reference results on the matched serum specimens were retested in duplicate. The results that occurred 2 out of 3 times were recorded as the final results. Samples from the commercial serum/plasma seroconversion panels giving discordant results were not retested.

4.4 Data analysis

4.4.1 Sensitivity, specificity, confidence limits (CL) and predictive values of anti-HIV tests The formula for calculation of sensitivity, specificity and predictive values is represented diagrammatically in the table below. Calculation of sensitivity, specificity and predictive values True anti-HIV status

+ –

Results of assay + a

True-positives b

False-positives a+b

under evaluation

– c False-negatives

d True-negatives

c+d

a+c b+d Sensitivity = a/(a+c) Positive predictive value = a/(a+b) Specificity = d/(b+d) Negative predictive value = d/(c+d)

Sensitivity: is the ability of the assay under evaluation to identify correctly specimens that contain antibody to HIV (reference assays positive). Thus, sensitivity is the number of true positive specimens recognized by the assay under evaluation as positive, divided by the number of specimens identified by the reference assays as positive, expressed as a percentage.

Specificity: is the ability of the assay under evaluation to identify correctly specimens that do not contain antibody to HIV (reference assays negative). Thus specificity is the number of true negative specimens recognized by the assay under evaluation as negative, divided by the number of specimens identified by the reference assays as negative, expressed as a percentage.

NOTE: Specimens that gave indeterminate results with the assays under evaluation were included in the analyses as a false result.

Confidence limits (CL): the 95% confidence limits are a means of determining whether observed differences in sensitivity or specificity between assays are significant or not. Exact 95% confidence limits for Binomial proportions were calculated from the F-distribution (Armitage P. and Berry G. Statistical Methods in Medical Research, 2nd Edition. Blackwell Scientific Publications, Oxford, 1987, page 119).

Predictive Values:

The positive predictive value (PPV) is the probability that when the test is reactive, the specimen does contain antibody to HIV. This may be calculated in two ways:

1. using the simple formula a/(a+b) which will give an approximate value (see Table C).

2. using the more precise formula which takes the prevalence of HIV in the

population into account (prevalence)(sensitivity) PPV= ____________________________________________

(prevalence)(sensitivity) + (1 - prevalence)(1 - specificity) The negative predictive value (NPV) is the probability that when the test is negative,

a specimen does not have antibody to HIV. This may be calculated using: 1. the simple formula d/(c+d) which will give an approximate value (see Table C). 2. the more precise formula which takes the prevalence of HIV in the population

into account: (1 - prevalence)(specificity) NPV= _____________________________________________

(1 - prevalence)(specificity) + (prevalence)(1 - sensitivity)

The probability that a test will accurately determine the true infection status of a person being tested varies with the prevalence of HIV infection in the population from which the person comes. In general, the higher the prevalence of HIV infection in the population, the greater the probability that a person testing positive is truly infected (i.e., the greater the positive predictive value [PPV]). Thus, with increasing prevalence, the proportion of false-positive decreases; conversely, the likelihood that a person showing negative test results is truly uninfected (i.e., the negative predictive value [NPV]), decreases as prevalence increases. Therefore, as prevalence increases, so does the proportion of samples testing false-negative. However, this effect only becomes apparent at prevalence of 80% and above.

4.4.2 Inter-reader variability

The inter-reader variability was calculated as the percentage of specimens for which initial test results were differently interpreted (i.e. positive, negative or indeterminate) by the independent readers.

4.4.3 Sensitivity in seroconversion panels

The results obtained with commercial serum/plasma early seroconversion panels using the assays under evaluation were compared with those obtained using Enzygnost Anti-HIV 1/2 Plus (Behringwerke AG), the assay arbitrarily designated the reference for determination of relative sensitivity in these panels. For each seroconversion series

(panel) the first specimen in the sample sequence to become reactive with Enzygnost Anti-HIV 1/2 Plus (Behringwerke AG) was assigned the value “0”. Results from the assays under evaluation were compared with Enzygnost Anti-HIV 1/2 Plus (Behringwerke AG) by determining the difference between the specimen assigned value“0” and the relative position in the sample sequence of the first specimen which showed a reactive result with each of the assays under evaluation. For example, if an assay became reactive two specimens earlier in a series than Enzygnost Anti-HIV 1/2 Plus (Behringwerke AG), the value assigned for that series in that assay was -2. Similarly, if an assay became reactive one specimen later than Enzygnost Anti-HIV 1/2 Plus (Behringwerke AG), the value assigned was +1. If no specimens in the panel are positive then the assigned value was 1+ the total number of specimen in the panel. The assigned values over the 8 seroconversion series were averaged to determine a mean relative seroconversion sensitivity index for each assay and the 95% confidence limits were determined. The results for the seroconversion panels are presented in Table 6 and diagrammatically in figure 1.

4.4.4 Additional analyses

The technical aspects of the assays under evaluation were assessed by the technician who performed the testing. These assessments, along with other selected assay characteristics, contributed to an overall appraisal of each assay’s suitability for use in small laboratories. To enable comparison between assays, an arbitrary scoring system was used to rate specified assay characteristics.

5. ASSAY EVALUATIONS

Results from the testing of the HIV whole blood and seroconversion panels are presented in Tables 2 and 6 and figure 1 on the following pages. Of the seven assays, six obtained 100% sensitivity and one obtained 98.8% in the positive panel tested. Care should be taken when interpreting these results as only a small number of positive samples (n=80) was tested and evaluation on a larger panel including specimens from other geographical regions is required to confirm these findings. Four kits obtained specificity of 100%, and the other 3 obtained 97.6%, 98.8% and 99.4% respectively. The results for both sensitivity and specificity should be interpreted carefully and by taking the 95% confidence limits (95%CL) into account.

Many of these assays have been evaluated in serum/plasma panels previously by WHO and other groups. The Determine HIV-1/2 (Abbott), Capillus HIV-1/2 (Trinity Biotech) and UniGold HIV (Trinity Biotech) have been evaluated on serum/plasma panels previously by WHO. This information is available on the WHO website www.who.int/bct . However, the focus of this evaluation was specific in assessing the performance of these 7 S/R anti-HIV tests on whole blood samples.

ASSAY EVALUATIONS

Whole Blood Specimens

Table 1. General characteristics and operational aspects Name

Determine™

HIV-1/2

InstantScreen™ Rapid HIV-1/2

Assay*

ADVANCED QUALITY™

Rapid HIV Test

MedMira Rapid HIV

Test

First Response™ HIV-1/HIV-2 WB

CAPILLUS™ HIV-1/HIV-2

Uni-Gold™ HIV

Company

Abbott Laboratories, Dainabot Co. Ltd.,

Tokyo, Japan

GAIFAR GmbH, Potsdam, Germany

InTec Products Inc.,

Xiamen, China

MedMira Laboratories Inc.,

Halifax, Canada

PMC Medical Pty. Ltd.,

Daman, India

Trinity Biotech PLC,

Bray, Ireland

Trinity Biotech PLC,

Bray, Ireland

Assay type immunochromatographic immunofiltration immunochromatographic immunofiltration immunochromatographic agglutination immunochromatographic

Solid phase membrane membrane membrane membrane membrane polystyrene latex beads

membrane

Antigen type recombinant/synthetic epitope-combi-antigens

recombinant synthetic recombinant recombinant recombinant

Specimen type

optional

whole blood

serum/plasma

whole blood

serum/plasma

whole blood

serum/plasma

whole blood

serum/plasma

whole blood

serum/plasma

whole blood

serum/plasma

whole blood

serum/plasma

Number of tests per kit

(product code)

100

(7D23-33)

20

(not available)

40

(ITP02002-TC40)

50

(not available)

35

(DD/138)

100

(6048G)

20

(1206502)

Lot numbers evaluated (expiry date)

62509U102 (13/4/2001)

Gen 1: 01199 (12/2000)

Gen 1: ISO1499 (12/2000)

Gen 2: ISO 1700 (01/2001)

RD 0907019 (10/2001)

CTIA 0009 (5/2001)

300D12 (8/2001)

G35412 (13/3/2001)

G32307 (03/02/2001)

Shelf life

( at °C)

18 mths

(2 – 30)

18 mths

(-20 to +45)

18 mths

(2 – 30)

1 year

(2 – 30)

18 mths

(2 – 30)

20 mths

(2 – 8)

20 mths

(2 – 27)

Volume of whole blood needed (µl)

Final dilution of whole blood

50

none

20

none

5

1/21

≈ 30

none

30

none

10

1/13

≈ 60

none

Total time to perform the assay: h.min. (1 specimen)

0.17

0.03

0.01

0.05

0.01

0.03

0.11

Reading

visual visual visual visual visual visual and/or by Capillus Digital

Reader

visual

Price/test (US$) 1.20 8 - 12 0.80 – 1.20 3 1.15 2.20 2.34

*Two versions of the InstantScreen assay were evaluated, Generation 1 and Generation 2.

Page 13

Table 2. Comparison of the whole blood HIV assays with reference test Name

Determine™ HIV-1/2


Assay*

ADVANCED QUALITY™

Rapid HIV Test

MedMira Rapid HIV Test

First Response™ HIV-1/HIV-2

WB


Uni-Gold™ HIV

Final sensitivity % (95 CL)1

n=80

100.0 (95.5 – 100.0) Gen 1: n=46

98.0 (89.0 – 100.0)

Gen 2: n=34

100.0 (90.0 – 100.0)

98.8 (93.2 – 100.0) 100.0 (95.5 – 100.0) 100 (95.5 – 100)

100.0 (95.5 – 100.0) 100.0 (95.5 – 100.0)

Initial specificity % (95 CL)

Final specificity % (95 CL)

n=170

99.4 (96.7 – 100.0)

99.4 (96.7 – 100.0)

Gen 1: n= 62

98.0 (91.0 – 100.0)

Gen 2: n=108

99.0 (95.0 – 100.0)

Gen 1: n= 62

98.0 (91.0 – 100.0)

Gen 2: n=108

100.0 (97.0 – 100.0)

97.5 (91.3 – 99.7)

100.0 (97.9 – 100.0)

91.2 (85.9 – 95.0)

97.6 (94.1 – 99.6)

98.2 (94.9 – 99.6)

98.8 (95.8 – 99.9)

100.0 (97.9 – 100.0)

100.0 (97.9 – 100.0)

100.0 (97.9 – 100.0)

100.0 (97.9 – 100.0)

Indeterminate results % 0.0 Gen 1: 0.0

Gen 2: 0.0

0.8 0.8 0.0 0.0 0.0

Initial inter-reader variability % 1.6 Gen 1: 0.0

Gen 2: 0.7

2.0 14.4 0.4 0.0 0.4

PPV 0.1%2

6.0%

1.642

91.41

Gen 1: 0.05

Gen 2:100.0

Gen 1: 75.8

Gen 2: 100.0

100.0

100.0

0.412

72.67

0.832

84.18

100.0

100.0

100.0

100.0

NPV 0.1%

6.0%

100.0

100.0

Gen 1: 100.0

Gen 2: 100.0

Gen 1: 99.9

Gen 2: 100.0

100.0

99.9

100.0

100.0

100.0

100.0

100.0

100.0

100.0

100.0

195% Confidence Limits. 2 Please note that, due to the formula used, small differences in specificity may result in apparently large differences in PPV in low prevalence populations. * 46 and 34 HIV positive specimens of the whole blood panel were tested in the Generation 1 and Generation 2 InstantScreen assays, respectively, and 62 and 108 HIV negative specimens were tested in the Generation 1 and Generation 2 assays, respectively.

Page 14

Table 3. Detailed operational aspects Name

Determine™

HIV-1/2


Assay

ADVANCED QUALITY™

Rapid HIV Test



WB


Uni-Gold™ HIV

Dimension (cm) of kit: w-l-h

27 - 16 -1 30 - 19 - 9 22 - 13.5 - 9 37.5 - 27.5 - 9.5 21 - 12.3 - 7 22 - 16.5 - 6.5 23 - 14 - 10.5

Storage conditions (°C)

2 - 30 -20 – +45 2 - 30 2 - 30 2 - 30 2 - 8 2 - 27

Incubation temperature (°C)

room temperature none stated room temperature 20 - 30 room temperature room temperature room temperature

Reading endpoint stability

(h.min)

1.0 >24.00 0.01 - 0.20 0.15 0.10 0.30 0.20

Stability after dilution/

Reconstitution/opening (°C)

- antigen

- controls

- sample diluent

- conjugate

- substrate

- wash buffer

expiry date (2 - 30)

not applicable

not applicable


not applicable


expiry date (-20 – +45)

not applicable



not applicable



not applicable


not applicable

not applicable

not applicable


1 week (2 - 8)

not applicable

1 week (2 - 8)

not applicable

expiry date (2 - 8)


not applicable

not applicable

not applicable


not applicable

expiry date (2 - 8)

expiry date (2 - 8)

not applicable

not applicable

not applicable

not applicable


not applicable

not applicable

not applicable

not applicable


Number of sera per run

Minimum - maximum

1 - 10

1 - 5

1 - 5

1 - 5

1 - 5

1 - 10

1 - 10

Number of controls per test run

- negative

- cut-off/weak positive

- positive

- blank

internal control: reagent control

: sample addition

control

0

0

0

0

1

0

0

0

0

0

0

1

0

0

0

0

1

0

1

0

1

0

0*

0

0

0

0

0

0

1

1

0

1

0

0

0

0

0

0

0

1

0

* Version 1 of the MedMira HIV Rapid test does not contain a reagent control. The later version 2 of the assay contains a reagent control line.

Page 15

Table 3. (continued) Detailed operational aspects Name



Assay

ADVANCED QUALITY™

Rapid HIV Test



WB


Uni-Gold™ HIV

Estimated time to perform one run: h. min

0.17 0.03 0.01 0.05 0.01

0.03 0.11

Equipment needed but not provided in the kit1:

- washer

- incubator (water-bath)

- spectrophotometric reader

- refrigerator (storage)

- agitator, rocker

- aspiration device

- automatic pipette (µl) - multichannel pipette (µl)

- disposable tips

- dilution tubes/rack, microtiterplate

- distilled or deionised water

- plate covers

- graduated pipette; cylinder (ml)

- sulfuric acid/sodium hydroxide

- absorbent paper

- disinfectant

- gloves

- reagent trough

- timer

-

-

-

-

-

-

+/-

-

+/-

-

-

-

-

-

-

-

+

-

+

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

+

-

-

-

-

-

-

-

-

+

-

+

-

-

-

-

-

-

-

+

-

+

-

-

-

+

-

-

-

-

-

-

-

-

-

-

-

-

+

-

-

-

-

-

+

-

-

+

-

+

-

-

-

-

-

-

-

+

-

+

-

-

-

+

-

-

-

-

-

-

-

-

-

-

-

-

+

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

+

-

+

Definition of positive results Appearance of red control and

patient bars

Appearance of blue test and control dots

Appearance of test and control lines

Appearance of distinct red dot

Appearance of pink-purple test and control lines

Appearance of any agglutination

Appearance of test and control lines

Definition of grey zone or

Indeterminate result

Not applicable Not applicable Not applicable Not applicable Not applicable * Not applicable

1+: not provided in the kit but necessary to perform the test: -: provided in the kit or not necessary to perform the test; +/-: use is optional. * When using the optional photometer a 'Threshold' reading is displayed.

Page 16

Table 4a. Technician's appraisal of the test kit Name

Score Determine™

HIV-1/2


Assay

ADVANCED QUALITY™

Rapid HIV Test

MedMira Rapid HIV

Test

First Response™

HIV-1/HIV-2 WB


Uni-Gold™ HIV

Number of steps in the test procedure:

- 1-2 steps

- 3-5 steps

- >5 steps

6

3

1

6

3

6

1

6

6

6

Clarity of kit instructions:

- good

- needs improvement

2

1

2

1

1

2

2

2

2

Kit and reagent packaging and labelling:

- good

- needs improvement

2

1

2

2

2

2

1

2

2

Total (out of possible 10)

10 10 6 9 5 9 10 10

Comments on the test kit Control samples should be used with this test.

Sample volumes, time periods and

storage conditions information in the kit insert could lead to misunderstanding. These should be

defined precisely.

Migration of sample/conjugate

mixture not completed in all cases within time limit of 20

minutes.

Red cells observed after removal of pre-filter for 5

samples

Control samples should be used with this test.

Outer packaging and components

should be labelled with kit name and

expiry date.

The kit insert provided did not give details of procedure for

testing whole blood specimens,

however it has since been updated.

Control samples should be used with this test.

Page 17

Table 4b. Calculation of ease of performance Name


InstantScreen™ Rapid HIV-1/2 Assay (Gen2)

ADVANCED QUALITY™

Rapid HIV Test

MedMira Rapid HIV

Test


WB


Uni-Gold™ HIV

Need to prepare:

- antigen - substrate - wash solution - conjugate - predilution of serum

11 1 1 1 1

1 1 1 1 02

1 1 1 1 1

1 1 1 0 1

1 1 1 1 1

1 1 1 1 1

1 1 1 1 1

Stability after dilution/opening:

(expiry date = 1; less = 0)

- antigen

- controls

- sample diluent

- conjugate

- substrate

- wash buffer

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

0

1

0

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

Sufficient reagents

- wash buffer (yes = 1; no = 0)

1

1

1

1

1

1

1

1

1

1

1

1

1

1

Item needed but not provided in the kit:

- reagent trough

- automatic/multichannel pipette

- dilution - tubes, rack/microtiter plate

- distilled or deionised water

- plate covers

- graduated pipette, cylinder

- sulfuric acid/sodium hydroxide

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

0

1

1

1

1

1

1

1

1

1

1

1

1

1

0

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

Technician's appraisal of the test kit3

(rating out of 10)

10 6 9 5 9 10 10

Total (out of possible 30) 30 25 28 22 28 30 30

Ease of performance: - less easy <20 - easy 20 # x # 25 - very easy >25

very easy

very easy

very easy

easy

very easy

very easy

very easy

11 : positive rating: reagent needs no preparation; item provided in the kit 20 : negative rating: reagenàpt needs preparation; item not provided in the kit 3 : see table 4a

Page 18

Table 5. Suitability for use in small laboratories

Name

Score Determine™

HIV-1/2


Assay

ADVANCED QUALITY™

Rapid HIV Test

MedMira Rapid HIV

Test


WB


Uni-Gold™ HIV

Sensitivity - 100% - 98 - 100% - <98% Specificity - >98% - 95 - 98% -<95% Incubation temperature - room t° - other than room t° Shelf-life - >1 year - ∃ 6 months # 1 year - < 6 months Storage at - ambient t° possible (opened kit) - ambient t° possible (unopened kit) - 2-8°C required Price per test (US$) - #1.0 - #2.0 - > 2.0 Ease of performance - very easy - easy - less easy Rapidity of performance: 1 serum - < 10 min - 10 – 30 min - > 30 min Washer/agitator - not needed - needed Reading - visual: inter-reader variability #3% : inter-reader variability >3%

- reading equipment

5 3 0

5 3 0

3 1

3 2 1

5 2 1

3 2 1

5 3 1

3 2 1

3 1

5 3 1

5

5

3

3

5

2

5

2

3

5

5

5

3

3

5

1

5

3

3

5

3

3

3

3

5

2

5

3

3

5

5 3 3 3 5 1 3 3 3 3

5 5 3 3 5 2 5 3 3 5

5

5

3

3

1

1

5

3

3

5

5

5

3

3

5

1

5

2

3

5

Total (out of possible 40) 38 38 35 32 39 34 37

Suitability for use in small laboratories:

- less suitable < 23

- suitable # x # 30

- very suitable > 30

very suitable

very suitable

very suitable

very suitable

very suitable

very suitable

very suitable Page 19

Table 6. Performance on commercial serum/plasma seroconversion panels

INNO-LIA HIV Confirmation Panel ID Bleed date

Days since first

bleed

Abbott

HIV-AG ratio*

Enzygnost Anti-HIV 1/2 Plus

OD/CO

SR1 SR2 SR3 SR4 SR5 SR6 SR7

sgp120 gp41 p31 p24 p17 sgp105 gp36 Result

PRB910 -01 11.05.89 0 0.4 0.1 neg neg neg neg neg neg neg - - - - - - - neg -02 25.05.89 14 5.7 0.1 neg neg neg ind neg neg neg - - - - - - - neg -03 06.06.89 26 0.6 >6.7 pos pos pos pos pos pos pos 2+ 3+ - 2+ 2+ - - HIV-1 -04 08.06.89 28 0.5 >6.7 pos pos pos pos pos pos pos 2+ 3+ - 2+ 2+ - - HIV-1 -05 13.06.89 32 0.4 >6.7 pos pos pos pos pos pos pos 2+ 3+ - 2+ 2+ - - HIV-1 -06 15.06.89 35 0.4 >6.7 pos pos pos pos pos pos pos 2+ 3+ - 2+ 2+ - - HIV-1 -07 20.06.89 40 0.4 >6.7 pos pos pos pos pos pos pos 2+ 3+ - 2+ 2+ - - HIV-1

PRB912-01 14.02.90 0 10.2 1.8 neg neg neg pos pos neg neg - - - - - - - neg -02 23.02.90 9 24.9 >6.7 pos pos pos pos pos pos pos - 3+ - 2+ 2+ - - HIV-1 -03 28.02.90 14 10.6 >6.7 pos pos pos pos pos pos pos - 3+ - 2+ 2+ - - HIV-1 -04 02.03.90 16 3.2 >6.7 pos pos pos pos pos pos pos - 3+ - 2+ 2+ - - HIV-1 -05 14.03.90 28 0.5 >6.7 pos pos pos pos pos pos pos - 3+ - 2+ 2+ - - HIV-1 -06 16.03.90 30 0.5 >6.7 pos pos pos pos pos pos pos - 3+ - 2+ 2+ - - HIV-1

PRB914-01 12.01.90 0 0.4 >6.7 pos pos neg pos pos pos pos 1+ 2+ - 1/- - - - HIV-1 -02 16.01.90 4 0.5 >6.7 pos pos neg pos pos pos pos 1+ 2+ - 1+ - - - HIV-1 -03 19.01.90 7 0.5 >6.7 pos pos neg pos pos pos pos 1+ 2+ - 2+ 1+ - - HIV-1 -04 06.02.90 28 0.4 >6.7 pos pos neg pos pos pos pos 2+ 2+ - 2+ 2+ - - HIV-1 -05 12.02.90 31 0.4 >6.7 pos pos neg pos pos pos pos 2+ 2+ - 2+ 2+ - - HIV-1

PRB917-01 15.10.90 0 0.4 0.6 neg neg neg neg neg neg neg - - - - - - - neg -02 07.12.90 53 3.9 0.1 neg neg neg neg neg neg neg - - - - - - - neg -03 11.12.90 57 21.6 0.2 neg neg neg pos neg neg neg - - - - - - - neg -05 19.12.90 65 2.4 >6.7 pos pos neg pos pos pos pos 1+ 2+ - 1/- - - - HIV-1 -06 21.12.90 67 1.6 >6.7 pos pos pos pos pos pos pos 1+ 2+ - 1+ - - - HIV-1

PRB927-01 10.02.94 0 0.6 0.1 neg neg neg neg neg neg neg - - - - - - - neg -02 10.03.94 28 >22,7 2.2 neg neg neg neg neg neg neg - - - - - - - neg -03 15.03.94 33 10.2 >6.7 pos pos neg pos pos pos pos - 2+ - - - - - ind -04 17.03.94 35 2.6 >6.7 pos pos pos pos pos pos pos 1+ 2+ - - - - - HIV-1 -05 22.03.94 40 1.3 >6.7 pos pos pos pos pos pos pos 2+ 3+ - 2+ 2+ - - HIV-1

PRB928-01 25.03.94 0 0.6 0.1 neg neg neg neg neg neg neg - - - - - - - neg -02 14.07.94 111 >22,7 4.8 pos pos neg pos pos neg pos - 1+ - - - - - neg -03 23.07.94 120 2.2 >6.7 pos pos pos pos pos pos pos - 3+ - 2+ - - - HIV-1 -04 28.07.94 125 1.8 >6.7 pos pos pos pos pos pos pos 1+ 2+ - 2+ 1+ - - HIV-1 -05 02.08.94 130 1.0 >6.7 pos pos pos pos pos pos pos 2+ 3+ - 2+ 2+ - - HIV-1

Page 20

Table 6. continued Performance on commercial serum/plasma seroconversion panels

INNO-LIA HIV Confirmation Panel ID Bleed date

Days since first

bleed

Abbott

HIV-AG ratio*

Enzygnost Anti-HIV 1/2 Plus

OD/CO

SR1 SR2 SR3 SR4 SR5 SR6 SR7

sgp120 gp41 p31 p24 p17 sgp105 gp36 Result

PRB930-01 21.06.95 0 0.9 0.1 neg neg neg neg neg neg neg - - - - - - - neg -02 24.06.95 3 2.7 0.1 neg neg neg neg neg neg neg - - - - - - - neg -03 28.06.95 7 4.2 4.5 pos neg neg neg pos neg pos - 1+ - - - - - ind -04 01.07.95 10 12.8 >6.7 pos pos neg pos pos pos pos - 2+ - 2+ - - - HIV-1

PRB944-01 03.09.96 0 0.5 0.1 neg neg neg neg neg neg neg - - - - - - - neg -02 05.09.96 2 1.0 0.1 neg neg neg neg neg neg neg - - - - - - - neg -03 10.09.96 7 6.6 0.1 neg neg neg neg neg neg neg - - - - - - - neg -04 12.09.96 9 7.0 0.2 neg neg neg neg neg neg neg - - - - - - - neg -05 17.09.96 14 5.8 5.0 pos pos neg pos pos pos pos - 2+ - 1+ - - - HIV-1 -06 19.09.96 16 3.2 >6.7 pos pos pos pos pos pos pos - 2+ - 2+ - - - HIV-1

Notes: *Data provided by BBI. OD/CO = optical density value of speciemn/calculated cut off value SR1: Determine™ HIV-1/2 (Abbott Laboratories) SR4: MedMira Rapid HIV Test (MedMira Laboratories Inc.) SR7: Uni-Gold™ HIV (Trinity Biotech PLC) SR2: InstantScreen™ Rapid HIV-1/2 Assay (GAIFAR GmbH) SR5: First Response™ HIV-1/HIV-2 WB (PMC Medical Pty. Ltd) SR3: ADVANCED QUALITY™ Rapid HIV Test (InTec Products Inc.) SR6: CAPILLUS™ HIV-1/HIV-2 (Trinity Biotech PLC)

Page 21

FIGURE 1: RELATIVE PERFORMANCE OF ANTI-HIV ASSAYS IN COMMERCIAL SERUM/PLASMA SEROCONVERSION

PANELS AS COMPARED TO THE REFERENCE ASSAY (ENZYGNOST ANTI-HIV 1/2 PLUS)

-3.5

-2.5

-1.5

-0.5

0.5

1.5

2.5

3.5

average

95% confidence limits

Detection Before Reference Assay

Detection After Reference Assay

Determine HIV-1/2

InstantScreen Rapid HIV-1/2

ADVANCED QUALITY Rapid

HIV Test

MedMira Rapid HIV

Test

First Response

HIV-1/HIV-2 WB

CAPILLUS HIV-1/HIV-2

Uni-Gold HIV

Page 22

Explanatory notes for Tables 1-6 and Figure 1

Table 1 General characteristics and operational aspects of the assays.

Specimen type and volume All seven assays under evaluation may be used with human whole blood, serum or plasma samples. The volume of whole blood required for each assay ranged from 5µl to 60µl.

Shelf life at (°C) Only one kit, the Capillus HIV-1/HIV-2 required storage at 2 – 8°C, the remaining six kits could be stored at room temperature.

Final dilution of the serum

is the dilution of the serum in the test format, e.g. 10µl serum added to 200µl diluent gives a final dilution of 1/21.

Total time to perform the assay reflects the time needed to carry out 1 test

Price/test The indicative catalogue price, in US $, as given by the manufacturer, or converted to USD using the currency conversion rate at the time.

Table 2 Comparison of the results of the assays with reference tests

Sensitivity calculated as described on page 9 of this document.

Specificity calculated as described on page 9 of this document.

95% Confidence limits (CL) calculated as described on page 9 of this document

PPV and NPV calculated as described on page 9 of this document

Indeterminate results Simple/rapid assays - test results which could not be interpreted as clearly positive or negative were considered indeterminate.

Inter-reader variability

calculated as described on page 10 of this document.

Table 3 Detailed operational aspects of the assay

Number of specimens per run Minimum - maximum

- minimum number = 1 sample in addition to the required controls - maximum number = the maximum number of samples in addition to the required controls which can be simultaneously tested within

the limits of the assay procedure.

Page 23

Explanatory notes for Tables 1-6 and Figure 1

Table 3 cont. Number of controls per test run Internal control

Detailed operational aspects of the assay The InstantScreen Rapid HIV-1/2 assay (GAIFAR) has a control spot on the test devices which checks that sample has been added, the procedure is followed correctly and reagents function correctly. The Capillus HIV-1/HIV-2 (Trinity Biotech) assays contains no internal control. The original MedMira HIV Rapid Test provided for the evaluation contained no internal control, however a further version was supplied for the seroconversion panels which contained a procedural control line. The remaining four assays have a control spot or line on the test devices which checks that reagents function correctly and the procedure has been correctly followed.

Definition of positive results a sample is interpreted as positive according to the criteria set by the manufacturer and summarised in the table

Tables 4a and 4b Calculation of ease of performance of the assay

The criteria for this calculation are given in the respective tables.

Table 5

Suitability of the assay for use in small laboratories

The criteria for this calculation are given in the respective table. These criteria are primarily technical and while an assay may be regarded as “technically” suitable for use in laboratories with limited facilities or where small numbers of samples are routinely tested, the sensitivity and specificity of the assay are over-riding factors in determining the suitability of an assay for use in any laboratory.

Table 6 Performance of the assays on seroconversion panels An assay’s performance on the seroconversion panels should be viewed against both the sensitivity and specificity of the assay. Assays of relatively low specificity may appear to detect antibody to HIV earlier than other assays of higher specificity. Caution should be taken when reviewing seroconversion performance of assays tested only in 8 panels.

Figure 1 Relative performance on seroconversion panels Eight seroconversion panels (BBI), each containing several samples taken at different time intervals early in the infection period (window period), were tested with the simple and/or rapid anti-HIV test kits. The results obtained with these assays were compared with those of the combined outcome of the Enzygnost Anti-HIV 1/2 Plus reference test (see page 7 of this report); the difference in the relative position in the sample sequence for the first sample of a panel to become positive with test X as compared with the first positive result with the reference test. If a test gave a positive result earlier than the reference test the difference in detection was rated as negative; if the test became positive later the number was rated as positive. If the assay detected no specimens in the panel then the assigned value was 1 + total number of specimens in the panel. The mean of the difference in the number of specimens for a test to become positive as compared to the reference test was calculated and plotted on a yardstick. The 95% confidence limits of the mean were also calculated. These limits should be interpreted with caution as only 8 panels were tested.

Page 24

6 ANNEXES

ANNEX 1. Algorithm for characterisation of the WHO HIV whole blood matched serum specimen panel

EIA 1 Vironostika HIV Unifrom II plus (Organon Teknika)EIA 2: Enzygnost Anti-HIV 1/2 Plus, (Dade Behring)

+ + - -

POS NEG

HIV-1

HIV-2

dualreactive

PEPTI-LAV

1-2

INDETERMINATE Anti HIV NEGAnti HIV POS

+ - / -+

repeat ELISAS

IND

INNO-LIA HIV Confirmation

Western Blot

further

investigation: HIV Ag

+ - / -+

PCR

ANNEX 2. List of assay manufacturers’/distributors’ addresses Abbott Laboratories, . Diagnostics Division, 100 Abbott Park Road, Abbott Park, Il 60064-3500, USA. Tel: +1 847 937 6100; Fax: +1 847 938 2360; Website: www.abbott.com GAIFAR GmbH, Biotech Campus Hermannswerder 15-16, 14473 Potsdam, Germany. Tel: +49 331 298 3812; Fax +49 331 298 3849; Website: www.gaifar.com Intec Products Inc. (Xiamen), 332 Xinguang Road, Xin Yang Industrial Area, Haicang, Xiamen, China, 361022. Tel: +86 592 651 9666; Fax: +86 592 651 9159; Website: www.intecasi.com PMC Medical (India) Pvt. Ltd., Gala No. 32, 33 Shree Ganesh Industrial Estate, Kachigam, Nani-Daman, Daman-396210, India.

Tel: +91 02638 56774; Fax: +91 02638 56775; Website: www.premiermedcorp.com MedMira Laboratories Inc. 200 Ronson Drive, Suite 101, Toronto, Ontario, M9W 5Z9. Tel: +1 416 644 0011; Fax: +1 416 644 0007; Website: www.medmira.com Trinity Biotech PLC, IDA Business Park, Bray, Co. Wicklow, Ireland. Tel: +35 31 276 9800; Fax: +35 31 276 9888; Website: www.trinitybiotech.com 7 ADDITIONAL READING Additional reading may be obtained by visiting the BCT section of the WHO website at www.who.int/bct and follow the links to Key Initiatives and HIV Diagnostics. In addition to general information on diagnostics, assay evaluation reports for HIV, HCV and HBV are available as well as details for the WHO HIV Test Kit Bulk Procurement Scheme. 8 ACKNOWLEDGEMENTS We should like to thank the Institute of Tropical Medicine, Antwerp, Belgium for supplying the prospectively collected whole blood and matched serum samples that constituted the evaluation panel for this evaluation. We acknowledge the six companies, Abbott Laboratories, GAIFAR GmbH, Intec Products Inc., PMC Medical Pvt. Ltd., MedMira Laboratories Inc. and Trinity Biotech PLC for supplying the test kits free of charge. 9 NOTE Other HIV tests using whole blood were available at the time of this evaluation but, due to the nature, design and capacity of this prospective study, it was not possible to include them in the evaluation.

hiv assays: operational characteristics - who.int · prevalence of hiv infection, the probability...

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