IJM Editorial: Rapid oral fluid-based point-of-care HIV testing

[Guest guest]

IJM Editorial: Rapid oral fluid-based point-of-care HIV testing:

applicability in developing countries

Indian J Med Res 126, September 2007, pp 171-173

In India, specific high risk sub-populations (i.e. sex workers,

clients of sex workers, men who have sex with men and intravenous

drug users) and their interactions with susceptible populations (i.e.

spouses and partners) have created a complex heterogeneous HIV

epidemic1.

An estimated 5.7 million individuals were reported to be living with

HIV in India, although this estimate excludes individuals living with

undiagnosed HIV infection2,3. According to new estimates, 2.5 million

people in India are living with HIV4. Many factors may reduce the

acceptability and uptake of voluntary HIV counselling and testing,

and result in undiagnosed HIV.

These include stigma and discrimination by the community, health

professionals and the society at large2, poor awareness about

availability of testing and anti-retroviral treatment (ART) services,

lack of information on benefits of early detection and treatment.

Efforts to control the HIV epidemic in India can be undermined by

ongoing HIV transmission by

undiagnosed individuals. Although HIV prevalence in some southern

States is reported to be on a decline, to further control the

epidemic and to curtail its spread, it is essential to enhance HIV

testing, and reduce the number of undiagnosed individuals1.

To detect undiagnosed HIV, in a rapid, accurate, time and cost-

effective manner, high quality rapid point of- care HIV tests are

useful tools. A vast majority of rapid point-of-care HIV tests in

India are blood based (i.e. they require whole blood, plasma, serum,

or finger stick blood), while a few utilize alternative body fluids

such as oral fluid, saliva and urine5,6. Oral rapid point of-

care HIV tests score over blood-based HIV tests in their quality,

rapidity, convenience, ease of sample collection, and feasibility of

use in traditional and nontraditional settings7.

In India, widely used blood-based rapid HIV tests are based on older

technology such as dot-blot, often require laboratory technicians,

and take longer time (i.e. 30 min-2 h) to deliver results7. In

emergency settings (e.g. emergency wards and labour rooms), this may

be a disadvantage. In non-traditional outreach and rural settings,

laboratory technicians are not always available, and clients are

unlikely to return for receipt of test results when results are not

available immediately. In such

settings, rapid oral fluid point-of-care HIV testing may be an ideal

solution.

Why are tests referred to as oral fluid tests? Oral fluid-based HIV

tests sample oral mucosal transduate (OMT), an interstitial fluid

from the capillaries of the gingival gum margin8,9. OMT is a salivary

component, with a high concentration of IgG antibodies10. Currently,

two oral rapid point-of-care HIV tests are available in many

countries worldwide, and are currently

undergoing approval in India. OraQuick® ADVANCE HIV 1/2 (Orasure

Technologies Inc, PA, USA) is a US Food and Drug Administration (FDA)

approved test10. Calypte® AWARE HIV 1/2 (Calypte Biomedical

Corportation, OR, USA) is another rapid oral fluid test, but is not

currently FDA approved.

What data exist on the performance of oral fluid based HIV tests in

India? Recently, a study done in a rural hospital in Sevagram,

Maharashtra, found the oralfluid-based newer OraQuick® Rapid HIV1/2

test to be highly accurate7. When compared to a reference standard of

dual ELISA and Western Blot, the estimated sensitivity and

specificity was 100 per cent among 450 patients with suspected HIV7.

In comparison to blood based rapid tests and conventional testing

(i.e. ELISA

and Western Blot), the oral fluid-based test was the most preferred

test by the study participants7. In previous years, two other fairly

large studies of oral fluid testing in pregnant women were conducted

in urban settings11,12

..

In both studies, pregnant women in antenatal clinics and labour rooms

were tested with a battery of rapid HIV tests including OraQuick®

Rapid HIV saliva brush test. In the first study, 1244 pregnant women

in labour were tested with an earlier version of the OraQuick test

and a lower diagnostic accuracy (sensitivity 75%, specificity 100%)

was reported, probably due to the use

of a weak reference standard (i.e. ELISA)11. In the second study, of

1322 eligible women, 582 consenting pregnant women in labour and

delivery rooms were tested with many rapid tests including OraQuick®

Rapid HIV saliva brush test and 9 found HIV positive (1.6%) were

counselled successfully12. These studies have demonstrated that oral

fluid-based HIV tests can work well in both urban and rural settings.

In other settings worldwide, these tests have been well accepted by

clients and have reported high diagnostic performance13-15.

What concerns are to be kept in mind in the conduct of these tests?

Although the diagnostic accuracy of oral fluid-based tests is high,

their accuracy and clinical utility depend on disease prevalence,

clinical presentations of populations, and type of populations

tested6,8. Thus, false-positive, false-negative and nonreactive

results can occur with oral-fluid testing, as with

any rapid HIV testing. When isolated instances of false positives or

false negatives occur, diagnostic performance is often called into

question, and might result in good tests falling out of favour. For

example, reports of false-positive OraQuick oral tests created a lot

of concern and uncertainty in the United States a few years ago16. To

minimize test error, and obtain consistent, high quality results,

quality control and quality assurance procedures must be strictly

followed17.

These procedures involve running external serum controls after

opening each test kit lot, maintaining temperature logs in the

testing room, discarding poorly performing batches of kits and

maintaining quality assurance at all times even in outreach

settings17.

Further, certain medical conditions (i.e. lupus, syphilis, hepatitis,

IgM and IgG gammopathy) and interfering substances (i.e. heparin) can

produce non reactive results9. These conditions should be kept in

mind while interpreting test results6. Like any rapid point-of-care

test, oral fluid tests cannot, however, diagnose acute HIV infection.

Thus, re-testing high risk populations at three to six months

intervals, can detect seroconversions18.

Further, like all rapid tests, oral point of- care HIV test results

must be considered as

preliminary and require confirmation with reference standard tests

such as ELISA, Western Blot or immunofluorescence assays10,18.

What are the barriers and challenges in the widespread implementation

of oral fluid rapid tests in

India? In India, stigma is a major deterrent to effective uptake of

voluntary rapid testing3.

Therefore, testing programmes must provide client-centered, post-test

counselling sessions in a private setting where privacy and

confidentiality is priority. Also, it is known that

rural patients do not prefer to give blood specimens, due to cultural

reasons. Oral fluid specimens, therefore, may be more culturally

acceptable and feasible. This, in turn, can help expedite early

detection, and establish linkages to ART that may transform to

substantial cost savings in the long run.

In what settings are oral rapid tests useful? In occupational

exposure settings, oral tests can help

greatly to expedite diagnosis, thus reducing anxiety and help with

early use of ART in those exposed19.

Use of oral fluid tests in labour and delivery settings can expedite

delivery of interventions for reducing perinatal HIV

transmission11,13,20. Use of oral fluid based rapid HIV tests in

community based surveys can help estimate the true HIV burden in

India. Future studies on evaluating the impact of these tests on (i)

rapid delivery of interventions to reduce perinatal HIV transmission

in labour rooms, and (ii) behaviour modification of high risk clients

in outreach settings require investigation13. In developed country

settings, the use of oral fluid tests for home-based HIV self testing

is being actively pursued. The role for homebased self HIV testing in

developing countries such as India, is uncertain.

Several countries in Sub-Saharan Africa and Asia have approved the

use of oral fluid based point-of-care HIV tests (Quoc Pham, Director

Asia, Orasure Technologies, Inc, PA, USA, Personal Communication).

The time is ripe for their use in India to scale up HIV screening and

testing programmes. Their simplicity, versatility and feasibility

enable their implementation in various settings (e.g. voluntary

counselling and testing centres, private practitioners, outreach and

emergency settings). Incorporation of oral HIV tests could form part

of a multi-pronged prevention strategy in transforming the trajectory

of the HIV epidemic in India.

Conflict of Interest

Dr Pant Pai has no conflict of interest with Orasure Technologies,

Inc, PA, USA.

Acknowledgment

Dr Pant Pai is supported by a fellowship from the Canadian HIV Trials

Network (CTN).

Nitika Pant Pai

Canadian HIV Trials Network

McGill University Health Centre

Division of Infectious Diseases and

Immunodeficiency Service

Montreal Chest Institute

3650, St Urbain Street

Montreal, Quebec

Canada H2X 2P4

e-mail: nitika.pai@...

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