Diagnostic Evaluation
The INSTI HIV-1/HIV-2 antibody
test: a review
Ameeta E Singh†, Bonita Lee, Jayne Fenton & Jutta Preiksaitis
†
University of Alberta, Department of Medicine, Edmonton, AB, Canada
1.
Introduction
2.
Description of INSTI HIV-1 and
HIV-1/HIV-2 antibody tests
3.
Overview of clinical data on
INSTI HIV-1/HIV-2 antibody test
4.
Alternative technologies and
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comparison with INSTI HIV-1/
HIV-2 antibody test
5.
Conclusion
6.
Expert opinion
Introduction: Rapid HIV tests have been widely adopted globally as an
important component of HIV prevention and control programs. The INSTI
HIV-1/HIV-2 antibody test is a second-generation HIV antibody test, available
in most countries for use from whole blood, serum, and plasma.
Areas covered: Available data on kit characteristics and current performance
data on the INSTI HIV-1/HIV-2 antibody test are presented together with six
other rapid point-of-care tests (RPOCTs) for HIV antibody. Few published data
are available providing direct comparisons of INSTI with other RPOCTs for
HIV antibody and standard laboratory-based HIV-1/HIV-2 antibody assays.
Existing data showed that INSTI has comparable performance to other RPOCTs
but detected seroconversion later than standard laboratory-based assays.
Expert opinion: The good performance of INSTI HIV-1/HIV-2 antibody test,
its ease of use, the rapid availability of results (< 5 min), and the lack of
specialized equipment required to use the kit make this kit a useful addition
to the global market. The unique antigen and flow through technology
contained in the kit make it a strong addition to HIV RPOCTs and to
rapid/rapid algorithms used in many resource-limited settings.
Keywords: INSTI HIV-1/HIV-2 rapid test, rapid HIV testing
Expert Opin. Med. Diagn. [Early Online]
1.
Introduction
Rapid HIV tests have been widely adopted globally, particularly in resource-limited
settings, as an important component of HIV prevention and control programs
because they are ideal tools to increase the number of persons who are aware of their
HIV status and rapid availability of test results may improve prompt referral to care
and treatment services. Demographic and Health Survey data from 13 countries in
sub-Saharan Africa before 2006 found that only 2 -- 27% of population were aware
of their HIV status, and uptake of HIV testing ranged from 5 to 25% in men and
4 to 35% in women [1]. Another study in Kenya found that never tested and undiagnosed HIV-infected women had the highest proportion (39%) of missed testing
opportunities during an antenatal visit [2]. Although historical estimates of unknown
HIV infection in high-resource countries such as the United States have suggested
that around 20% are unaware of their HIV status [3], other studies suggested that
this may be an overestimate. A study in San Francisco, USA, reported that 10%
of HIV-infected persons were not aware of their status while another study in
Edmonton, Canada, reported that 5.6% were unaware of their HIV status [4,5].
Those who are unaware of their HIV status play a major role in the transmission
of HIV and propagation of the HIV epidemic [6-9].
Current rapid point-of-care tests (RPOCTs) for HIV offer many advantages
when compared to standard testing, fulfilling the “ASSURED” criteria (affordable,
sensitive, specific, user-friendly, robust and rapid, equipment-free, and deliverable)
required for point-of-care testing in developing countries [10]. Rapid HIV tests have
been of particular benefit in remote or resource-limited settings that may lack the
infrastructure for laboratory-based screening tests, in populations that are
10.1517/17530059.2013.774370 © 2013 Informa UK, Ltd. ISSN 1753-0059, e-ISSN 1753-0067
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1
A. E. Singh et al.
Article highlights.
.
.
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.
.
Rapid, point-of-care tests for HIV antibody have
transformed the ability to conduct testing for
HIV globally.
The INSTI HIV-1/HIV-2 antibody test, a second-generation
HIV antibody test, is available for use in most countries
for the detection of HIV-1 and HIV-2 from whole blood,
serum, and plasma.
Available data suggest that INSTI has comparable
sensitivity and specificity to other select RPOCT HIV
antibody tests for the detection of established HIV
infection, and limited data suggest that it may be better
than other HIV RPOCTs for the detection of early
HIV infection.
The INSTI HIV-1/HIV-2 antibody test has the fastest time
to results when compared to other select RPOCTs for
HIV antibody.
This box summarizes key points contained in the article.
traditionally more difficult to reach and where immediate
results can influence patient care [11]. Even in high-resource
countries, the ability to conduct the test in nontraditional
settings, the rapid availability of results (usually in < 30 min),
and the elimination of loss to follow up for test results may
make this testing approach preferable to centralized laboratory
screening in some settings [12].
The positive predictive value of screening assays is highly
dependent on the prevalence of the disease in the population.
Proportionally higher number of reactive screening results in
low-prevalence settings would represent false-positive results.
In resource-limited settings where Western blots (WBs) are
not readily available, two sequential rapid orthogonal (tests
that employ different antigens or principles) HIV-1/2
antibody tests are often used to confirm HIV diagnosis [11,13,14].
Delaney et al. also showed that a two-test algorithm can distinguish most true-positive from false reactive screening tests by
modeling data generated from an evaluation of US Food and
Drug Administration (FDA)-approved rapid tests [15].
In pregnant women, testing during labor provides the last
window of opportunity for interventions to decrease vertical
HIV transmission as interventions implemented during the
intrapartum or immediate postpartum period can still reduce
mother-to-child transmission [16]. A two-step strategy,
particularly parallel testing, improved diagnostic accuracy as
compared to a single test in a labor and delivery setting [17].
RPOCTs have now been widely employed in many developing country settings but despite global recommendations for
universal screening of all pregnant women, the uptake of
this strategy is suboptimal [18,19]. RPOCTs also have documented benefits in a variety of outreach settings such as
colleges, bathhouses, community-based organizations, and
populations including ethnic minorities, men who have sex
with men, and homeless individuals in San Francisco [20,21].
Several studies have confirmed the benefits and cost savings
of rapid testing in blood and body fluid exposures and noted
2
additional benefits including improved source patient
awareness of their HIV sero-status and increased compliance
with post-exposure reporting [22-25].
Cost analyses have suggested that RPOCT is cheaper per
test result delivered when compared with standard blood
testing [26]. However, it has been argued that RPOCT
estimates chronically underestimate the additional costs of
implementation, staffing, training, and maintenance that are
often excluded from estimated costs [27]. RPOCT also creates
new challenges with respect to training, maintenance of
competence, quality assurance, new kit lot verification,
post-marketing surveillance, and maintenance of public
health surveillance data [14].
A comprehensive review by Branson outlines the differences
between the three most commonly used generic assay formats
in rapid assays: particle agglutination, membrane immunoconcentration (flow-through) devices, and immunochromatographic
(lateral flow) strips [28]. Generally, flow-through and lateral
flow formats have shorter time for result when compared to
particle agglutination. Lateral-flow assays are typically stable
at room temperature while some flow-through assays require
refrigeration. The INSTI HIV-1/HIV-2 antibody test uses
the immunoconcentration (flow through) format but still
retains the advantage of stability at room temperature and
the time to result is short (Table 1). Quality control for the
materials and supplies used to produce the device is critical
for the performance of the assay as the test result is based on
subjective visual interpretation [29].
Description of INSTI HIV-1 and
HIV-1/HIV-2 antibody tests
2.
INSTI HIV-1/HIV-2 is made by a Canadian company,
bioLytical Laboratories, Inc., and was first licensed in
Canada for HIV-1 detection in November 2005 and the
license was amended to include HIV-2 detection in June of
2008. Although the kit contents available in the United States
are identical to that used in Canada and elsewhere, it is not yet
approved in the USA for HIV-2 detection; the INSTI
HIV-1 antibody test is US FDA approved for HIV-1 detection from whole blood, serum, and plasma [30]. The test
received CLIA waver from the US FDA in July 2012 [31]. In
Canada and elsewhere the INSTI HIV-1/HIV-2 antibody
test is available for the detection of HIV-1 and HIV-2
antibodies from whole blood, serum, and plasma.
INSTI has been CE Marked (a valid CE marking affixed
to a product indicates that it complies with the relevant
European “new Approach” product safety directives) for
HIV-1 and HIV-2 detection in Europe since March 2006.
This kit is the only licensed assay for HIV RPOCT in Canada
with Reveal G3 Rapid HIV-1 antibody test (MedMira, Inc.,
Nova Scotia, Canada) licensed for laboratory-based serum
and plasma testing only.
Since all countries but the United States have access to the
INSTI HIV-1/HIV-2 antibody test and because the majority
Expert Opin. Med. Diagn. [Early Online]
The INSTI HIV-1/HIV-2 antibody test
Table 1. Feasibility and acceptability of INSTITM HIV-1/HIV-2 antibody test.
Country
South Africa
Church-based settings
Canada
Community outreach -- female
sex workers
Newly registered patients in
primary-care setting
UK
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Clinical setting
France
Emergency room
Uganda
Canada
Clinic in urban market
Female sex workers
Feasibility and acceptability
N = 32, 54% were never tested for HIV;
87.5% consented to testing
N = 87, 32% were never tested for HIV;
100% consented to testing
N = 799, 55% were never tested for HIV;
67.4% of males and 80% of females
consented to testing
N = 8354, 67.5% consented to testing;
89.2% completed testing
N = 1104
N = 198
of the available performance data are from this version of the
kit, the descriptions that follow have been restricted to
this kit.
The INSTI HIV-1/HIV-2 antibody test is a manual, visually
read, flow-through immunoassay for the qualitative detection
of HIV-1/HIV-2 antibodies in human blood, serum, or plasma
(INSTI HIV-1/HIV-2 product monograph). The test contains
a synthetic filtration membrane above an absorbent material
within a plastic cartridge (the INSTI Membrane Unit). Company sources confirm that the recombinant HIV-1 gp41 and
HIV-2 gp36 antigens used in the kit are produced exclusively
for bioLytical Laboratories (personal communication, Rick
Galli, bioLytical Laboratories, Inc.). In addition, although the
flow-through technology used in the kit is not patent protected,
the INSTI solutions are proprietary and were developed to
work optimally with the HIV antigens (personal communication, Rick Galli, bioLytical Laboratories, Inc.). HIV-1/2
antibodies captured in the test spot react with a proprietary
chromatic agent, protein-A-indigo blue, to produce a colored
(blue) signal on the membrane. The membrane also contains
a procedural control which contains a protein-A treated spot
which captures IgG antibodies.
Kit contents, storage requirements, and
procedure for conducting test
2.1
There are different package formats of the INSTI HIV-1/
HIV-2 assay: single-use one-test kit with support materials
including alcohol swab, lancet, and pipette, for RPOCT or
package with 24 test units with or without the support materials. The testing components include an INSTI Membrane
Unit and three solutions: a sample diluent made of 5 ml
No. of infected
cases identified
Refs.
0
[44]
0
[42]
2
[45]
43 with positive
screen:
1 false-reactive result,
28 confirmed by WB,
4 known infected cases,
10 confirmatory test
results not available
121 tested positive
40 tested positive,
all known infection;
26% declined to receive
results at time of testing
including 3 with
reactive tests
[46]
[43]
[41]
Tris-glycerine buffer containing cell lysis reagents (Solution 1),
color developer (Solution 2), and clarifying solution (Solution 3)
with propriety components. All three vials contain 0.1%
sodium azide preservative and INSTI reagents are to be stored
at 15 -- 30 C, ambient temperature for most but not all settings.
The test is performed by adding the recommended amount
(50 µl) of whole blood, serum, EDTA-plasma, or EDTA
whole blood specimen to the vial of sample diluent which
lyses the red blood cells. The sample diluent-specimen
mixture is then poured into the well of the membrane unit.
If present, HIV-1/HIV-2 antibodies (IgG) are captured by
the recombinant HIV proteins in the test spot and IgG,
normally present in blood, is captured in the control spot.
Color developer is then added to the membrane unit.
A distinct blue dot should appear in the control spot area
and if HIV-1/HIV-2 antibodies are present, a blue color
will appear in the test spot area. Clarifying solution is then
added to decrease background color and make the control
and test spots more distinct.
Controls
Since IgG antibodies are present in both HIV-negative
and -positive human specimens, the internal control spot
provides a visual signal that the test was performed correctly
and IgG antibodies are present in the sample. If the control
spot does not appear then the test is considered invalid.
A panel of quality controls is available from the manufacturer
which includes a negative control and two positive controls, one
for HIV-1 and a second for HIV-2. Control panels are not run
with each sample but rather in accordance with local qualityassurance programs. Invalid results have been observed in
2.2
Expert Opin. Med. Diagn. [Early Online]
3
A. E. Singh et al.
some patients with low IgG level related to sepsis, immunosuppressed state, or extreme hemodilution; however, in one study,
no explanation could be found for two invalid tests [32].
Quality control (INSTI product monograph)
The manufacturer recommends that controls be run under the
following circumstances: for new INSTI operator verification
before performing testing on patient specimens, when
switching to a new lot number of INSTI test kits, when a
new shipment of kits is received, when temperatures in the
storage or testing area fall outside the recommended
15 -- 30 C (59 -- 86F) and at regular intervals as determined
by the user facility.
It is good laboratory practice to include positive and negative test controls at regular intervals as defined by the user
depending on the setting and for verification of new kit lot
or operator.
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2.3
Time to test interpretation (INSTI product
monograph)
2.4
Total test time varies depending on specimen type as well as
pre- and post-analytical processes but the actual performance
of the test and results of valid tests are typically available in
1 -- 2 min.
Safety considerations
The membrane unit is designed to filter, absorb, and retain
the specimen and all reagents to limit leakage. As with other
test kits for HIV, all specimens and controls should be
handled as if capable of transmitting infectious diseases
and it is recommended that BioSafety Level 2 practices or
equivalent precautions be observed [33].
2.5
Overview of clinical data on INSTI
HIV-1/HIV-2 antibody test
3.
There are few published or abstract data directly comparing
the INSTI HIV test with other RPOCTs. Available data on
the performance characteristics of INSTI HIV-1/HIV-2
antibody test are summarized in Table 2 [32,34-40]. Studies
assessing the feasibility and acceptability of the INSTI
HIV-1/HIV-2 antibody test in various clinical settings are
summarized in Table 1 [41-46].
Alternative technologies and comparison
with INSTI HIV-1/HIV-2 antibody test
4.
Seven RPOCTs for the detection of HIV antibody are currently
approved for use by the US FDA: OraQuick ADVANCE
Rapid HIV-1/2 antibody test (OraSure Technologies), Reveal
G3 Rapid HIV-1 antibody test (MedMira), Uni-Gold
Recombigen HIV (Trinity BioTech), Multispot HIV-1/
HIV-2 Rapid Test (Bio-Rad Laboratories), Clearview COMPLETE HIV-1/2 and Clearview HIV-1/2 STAT-PAK
(Chembio Diagnostics), and the INSTI HIV-1 antibody test.
4
Table 3 summarizes features of the six US FDA-approved
kits and the INSTI HIV-1/HIV-2 antibody test. All of these
tests use either immunochromatography (lateral flow) or
immunoconcentration (flow-through) techniques and contain
antigens that correspond to envelope regions of HIV-1 (gp41,
gp120, or both). Two of the tests (INSTI HIV-1/HIV-2
antibody test and the Bio-Rad Multispot HIV-1/HIV-2 test)
also contain HIV type 2 (HIV-2) envelope (gp36) antigens.
A recent study evaluated six tests (not including
INSTI HIV-1/HIV-2 antibody test) and showed reported
high sensitivity (95.38 -- 99.44%) and high specificity
(99.35 -- 99.98%) when compared to a Bio-Rad Enzyme
Immunoassay (EIA)/WB algorithm [47]. Of note, confidence
intervals overlapped among different tests and for different
specimen types. The sensitivity of some rapid tests was slightly
lower in specimens obtained from participants receiving antiretroviral therapy but the differences did not reach statistical
significance. This study also compared the sensitivity of the
rapid tests for detecting acute seroconversion to an IgMsensitive EIA. The EIA detected two WB-positive specimens
that had negative results on all rapid tests. In this study the
decreased sensitivity of rapid tests in detecting seroconversion
relative to the IgM-sensitive EIA was not statistically significant despite the high prevalence and high incidence of HIV
infections in the population studied. This is in contrast to
other studies using HIV RNA to detect HIV seroconversion [48,49]. Persons with a recent potential exposure who
may be seroconverting to HIV should be counseled and
retested or tested with a nucleic acid amplification test [7].
There are no published data directly comparing INSTI with
other rapid HIV tests and third- and fourth-generation HIV
EIAs. A study done at the Laboratory Branch, Division of
HIV AIDS Prevention, Centers for Disease Control and Prevention using plasma samples from HIV seroconvertors
showed that INSTI had higher sensitivity compared to the
six rapid tests in Delaney’s study in terms of earlier detection
of HIV antibodies before positive WB for these individuals
(Personal communication, Dr. Michele Owen, Centers
for Disease Control, Atlanta, USA). In the same evaluation,
INSTI detected seroconversion later than third- and
fourth-generation laboratory assays.
In addition to the seven US FDA-approved rapid tests,
there are many more rapid HIV tests on the global market
that have not received FDA approval (PATH) [50]. Performance of these assays in the developing world has been
well characterized in a variety of settings [51-54]. A recent
meta-analysis of RPOCT HIV kits also found that oral HIV
tests had lower sensitivity and lower positive predictive
value (PPV) than blood-based specimens in low-prevalence
populations than RPOCT that uses blood samples [55].
5.
Conclusion
The use of RPOCT for HIV has changed HIV testing practices worldwide and has vastly enhanced access to HIV testing
Expert Opin. Med. Diagn. [Early Online]
The INSTI HIV-1/HIV-2 antibody test
Table 2. Summary of published data on the performance of the INSTITM HIV-1/HIV-2 antibody test.
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Population (country)
Adults
Adults with documented HIV-1 or
HIV-2 infection (France)
Individuals with early seroconversion
HIV infection (Canada)
Pregnant women, source individuals
in blood and body fluid exposures,
acutely ill adults (Canada)
High-risk adults in outreach
settings (Canada)
Anonymous HIV testing clinic (Canada)
Archived and prospective samples in
community and hospital-based
clinics (Canada)
Anonymous HIV testing clinic (Canada)
Infants born to HIV positive mothers
HIV-exposed infants of known
HIV status (South Africa)
HIV-exposed infants (South Africa)
Specimen type
N (positive)
Performance
characteristic % (95% CI)
Refs.
Finger stick blood
200 (196*)
Sensitivity: 99 (96.3 -- 99.7)
[37]
Serum (stored)
49 (34)
Sensitivity: 69.4 (54.6 -- 81.8)
[38]
Serum
1708 (25)
Sensitivity: 100 (no CI available)
[32]
Finger prick
specimens
Finger prick
specimens
Serum and
whole blood
123 (2)
Sensitivity: 100 (no CI available)
[39]
4180 (71.6% male)
Sensitivity: 99.7% (99.5 -- 99.9%);
positive predictive value 82.4%
Depending on sample type:
sensitivity: 99.2 -- 99.6%;
specificity: 99.4 -- 99.9%
[35]
Specificity: 99.7% (99.5 -- 99.9%);
positive predictive value: 82.4%
[35]
Finger prick
specimens
3467 RPOCTs; 3462
whole blood EDTA
samples; 3462 plasma
samples; 1384 serum
samples
4180 (71.6% male)
[34]
Serum (stored)
273 (192)
Sensitivity: 70.3 (65.3 -- 75.40)
[36]
Whole blood
872
< 18 months: 254
< 3 months: 227
Sensitivity: < 18 months:
95.7 (92.4 -- 97.6)
< 3 months: 98.7 (96.2 -- 99.6)
[40]
*Four were weakly positive.
globally. In the maternal setting, particularly labor and delivery, RPOCT allows directed antiretroviral therapy to be given
to reduce mother-to-child transmission of HIV. In recipients
of blood and body fluid exposures, the availability of a rapid
test result in the source patient limits use of unnecessary
HIV post-exposure prophylaxis (PEP) and reduces anxiety
in the recipient. Finally, RPOCT for HIV has allowed populations to be reached that could not previously be reached in
traditional health-care settings.
Despite these many advantages, RPOCT for HIV has
resulted in new challenges to health systems. For example,
false-positive results with the RPOCT may result in unnecessary
anxiety and on occasion, unnecessary interventions may have
been implemented, e.g., the administration of antiretroviral
drugs at the time of delivery, HIV PEP, etc. [11]. In developed
countries, e.g., in outreach settings, individuals who screen positive still need to return for confirmatory tests so ideally; an
equally rapid confirmatory test represents a currently unmet
need in this setting unless a dual RPOCT algorithm becomes
universally accepted practice. Interestingly in the study by
Tyndall et al., some patients undergoing RPOCT declined to
receive the test results at the time of the test, including
some who tested positive, suggesting that HIV RPOCT may
not be the solution for HIV screening in all patients [41].
The available data suggest that INSTI has comparable
performance to other US FDA-approved RPOCT assays.
However, despite the potential public health benefits of
RPOCT for HIV, this form of testing also has limitations
compared to standard laboratory-based testing with lower
sensitivity, failing to identify cases of early HIV seroconversion [56]. Laboratory-based study suggested that rapid
fourth-generation HIV Ag/Ab testing assays might address
this concern [49]. However, further studies are required as initial field studies using an RPOCT combo assay: Determine
HIV-1/2 Ag/Ab Combo rapid test did not confirm this
advantage [57,58]. Some preliminary data suggest that the
INSTI test performed better than other RPOCT tests and
missed no HIV-infected infants when sequential antibody
tests were used to document loss of maternal HIV antibodies
in uninfected infants from settings where nucleic acid detection is not widely available for early diagnosis [40]. However,
infants on antiretroviral therapy were excluded from this
study and there was one falsely reactive test result by INSTI
in an uninfected infant > 18 months. Further data are necessary before recommendations regarding the use of the test in
this setting can be made.
Similar to standard testing, it will be important, with this
test as well as with other RPOCTs for HIV, to link HIVpositive persons to counseling and care services and those at
high risk to prevention services [59]. RPOCT also creates
new challenges with respect to training, maintenance of
competence, quality assurance, new kit lot verification,
Expert Opin. Med. Diagn. [Early Online]
5
6
gp41, gp36
gp41, gp36
Expert Opin. Med. Diagn. [Early Online]
Whole blood,
plasma, oral fluid
5
20 -- 40
Oral fluid: 99.3
(98.4 -- 99.7)
Whole blood:
99.6 (98.5 -- 99.9)
Plasma: 99.6
(98.9 -- 99.8)
Oral fluid 99.8
(99.6 -- 99.9)
Whole blood
100 (99.7 -- 100)
Plasma: 99.9
(99.6 -- 100)
Serum, plasma
10 -- 15
Serum and plasma:
100 (99.9 -- 100)
Serum: 99.9
(99.8 -- 100)
Plasma: 99.9
(99.8 -- 100)
30
Lateral flow
15 -- 37
Flow through
20 -- 30
Serum: 99.1
(98.8 -- 99.4)
Plasma: 98.6
(98.4 -- 98.8)
5
Serum: 99.8
(99.2 -- 100)
Plasma: 99.8
(99.0 -- 100)
50
Serum, plasma
Flow through
15 -- 27
gp41, g120
No
MedMira, Inc.,
Halifax, Nova Scotia,
Canada
Reveal
G3 rapid HIV-1
antibody test
Adapted from Campbell, 2009 [11], Cook, 2010 [38], Delaney, 2011 [47] and O’Connell, 2007 [61].
*INSTI data from product monograph.
NA: Not available.
Specificity
(95% CI) [47]
Specimen volume
required (µL)
Time to result (min)
Sensitivity
(95% CI) [47]
No
Yes
HIV-1/HIV-2
differentiation
HIV antigen and
antigen peptides
Test type
Test temperature
range ( C)
Sample types
OraSure Technologies,
Bethlehem,
Pennsylvania, USA
Bio-Rad Laboratories,
Redmond,
Washington, USA
Manufacturer
OraQuick
ADVANCE rapid
HIV-1/2 antibody test
Multispot
HIV-1/HIV-2
rapid test
Characteristic
Table 3. Overview of select RPOCT for HIV antibody.
Whole blood:
99.7 (99.0 -- 100)
Serum/plasma:
99.8 (99.3 -- 100)
10
Whole blood,
serum, plasma:
100 (99.5 -- 100)
Whole blood,
serum, plasma
50
Lateral flow
15 -- 27
gp41, gp120
No
Trinity Biotech, USA,
Jamestown,
New York, USA
Uni-GoldTM
Recombingen
HIV
Whole blood,
serum,
plasma: 99.9
(99.6 -- 100)
15 -- 20
Whole blood,
serum,
plasma: 99.7
(98.9 -- 100)
Whole blood,
serum, plasma
5
Lateral flow
18 -- 30
gp41, gp120
Chembio
Diagnostic
Systems, Inc.,
Medford,
New York, USA
No
Clearview
HIV1/2
STAT_PAK
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Whole blood,
serum, plasma:
99.9
(99.6 -- 100)
15 -- 20
Whole blood,
serum,
plasma: 99.7
(98.9 -- 100)
Whole blood,
serum, plasma
2.5
Lateral flow
18 -- 30
gp41, gp120
Chembio
Diagnostic
Systems, Inc.,
Medford,
New York, USA
No
Clearview
COMPLETE
HIV 1/2
1
Whole blood,
serum,
plasma: > 99%
(99 -- 99.6%)
Early
seroconversion [38]:
69.4 (54.6 -- 81.8%)
Whole blood,
serum, plasma:
>99.3 (99.3 -- 100%)
Whole blood,
serum, plasma
50
Flow through
15 -- 30
gp41, gp36
Yes
bioLytical
Laboratories, Inc.,
Richmond, British
Columbia, Canada
INSTITM
HIV-1/HIV-2
antibody test*
A. E. Singh et al.
The INSTI HIV-1/HIV-2 antibody test
post-marketing surveillance, and maintenance of public
health surveillance data.
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6.
Expert opinion
The available data on the INSTI HIV-1/HIV-2 antibody test
demonstrate comparable performance to other FDAapproved rapid HIV tests with slightly earlier detection of
infection than other RPOCT assays ([47], personal communication, Dr. Michele Owen). The studies have demonstrated
excellent performance when the test is conducted in nearsite laboratory settings as well as in the field. The kit meets
the WHO’s “ASSURED” criteria (affordable, sensitive, specific, user-friendly, robust and rapid, equipment-free, and
deliverable) with results available in most instances within
5 min, the fastest time to results compared to many other tests
on the global market. The plastic container which contains
the test well ensures that potentially infectious samples are
enclosed thereby reducing biological hazards, which makes it
logistically easier and safer to use in some field settings
compared to some other RPOCT formats.
The INSTI HIV-1/HIV-2 antibody test contains a unique
antigen and a novel flow-through technology, which makes it
an important addition to the field of HIV RPOCT for
screening as well as incorporation into a rapid/rapid testing
algorithm.
Three unmet areas have been identified for rapid HIV diagnostics: i) the determination of acute HIV infection; ii) early
infant diagnosis; and iii) vaccine-induced seroreactivity,
whereby individuals who have received HIV vaccines may
screen positive on rapid tests making distinguishing vaccination and disease impossible [14]. Better combination antigen/
antibody rapid assays or rapid tests based on nucleic acid
detection need to be developed to improve the diagnosis of
acute HIV seroconversion. Rapid tests based on antigen detection with high sensitivity and specificity or rapid assays based
on nucleic acid are also needed for early infant diagnosis. At
the present time, RPOCTs for HIV nucleic acid detection
are not commercially available but are in development [60].
Vaccine-induced seroreactivity is a difficult area that requires
diagnostic assays that can distinguish between antigens unique
to the vaccine versus natural viral antigens.
It is likely that HIV RPOCTs will have maximum impact
in areas that central laboratory testing cannot efficiently service [27]. To optimize the use of RPOCT HIV, an assessment
of the use of any given kit in a particular setting before implementation will be important to determine if the inclusion of
this type of testing has a positive effect on the epidemiology
(e.g., incidence) or patient outcomes [14]. Introduction of
the kit must be individualized to each setting particularly
where other tests and testing algorithms are already in place.
Local epidemiologic data should be used to determine the
sites that will be involved so that public health impact is maximized. Even though the majority of HIV RPOCTs are easy to
perform and appropriate for nonlaboratory settings, it is
critical that the accuracy and reliability of testing are ensured
by developing quality-assurance programs around the tests
themselves as well as ensuring that all testers are adequately
trained [14]. Field trials of these assays are necessary to validate
assay performance demonstrated in laboratory settings.
In developed countries where access to fourth-generation
laboratory-based HIV screening is readily available, caution
should be used when RPOCT is deployed in high-risk
settings. Parallel standard laboratory testing or follow-up
testing should be considered to ensure detection of highly infectious patients with early acute HIV infection. However, in
resource-limited settings, even when a rapid point-of-care technology is less sensitive or specific than the reference standard, its
implementation may still yield very important public health
benefits when standard laboratory testing is not accessible [27].
Future devices should combine rapid testing for multiple
infections (e.g., HIV, HBV, HCV, syphilis) and should further
explore newer rapid test technologies (e.g., fourth-generation
HIV antibody/antigen tests, and nucleic acid detection assays).
Finally, additional studies will be required to ensure that test
results are translated into the relevant services, e.g., linking of
HIV-infected infants to immediate care for initiation of treatment as per WHO recommendations and newly diagnosed
HIV-positive persons to counseling and care services [14,59].
Declaration of interest
The authors state no conflict of interest and have received no
payment in preparation of this manuscript.
Expert Opin. Med. Diagn. [Early Online]
7
A. E. Singh et al.
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Expert Opin. Med. Diagn. [Early Online]
Affiliation
Ameeta E Singh†1 BMBS MSc FRCPC,
Bonita Lee2 MD MSc FRCPC,
Jayne Fenton3 MLT &
Jutta Preiksaitis4 MD FRCPC
†
Author for correspondence
1
Clinical Professor,
University of Alberta,
Department of Medicine,
Division of Infectious Diseases,
c/o 3B20-11111 Jasper Ave, Edmonton,
AB, T5K 0L4, Canada
Tel: +1780 342 2300; Fax: +1780 425 2194;
E-mail: [email protected]
2
University of Alberta,
Edmonton Clinic Health Academy,
Department of Pediatrics, 3-588D - 11405
87 Avenue, Edmonton, AB, T6G 1C9, Canada
3
Provincial Laboratory for Public Health,
2B2.07-9440 112 St., Edmonton,
AB, T6G 2J2, Canada
4
University of Alberta, University Hospital,
Department of Medicine, 8-8440 112 ST NW,
2B2 WMC, Edmonton, AB, T6G 2J2, Canada