The OraQuick In-Home HIV Test was recently approved by the FDA advisory committee for sale over the counter. FDA regulators will take a decision in a few months' time. The committee felt that the benefits of the oral swab test far outweigh the risks of false positive and false negative test results.

Dr Nitika Pant Pai, Assistant Professor of Medicine in the Division of Clinical Epidemiology & Infectious Diseases at McGill University, has been focussing her research at developing synergistic packages with point-of-care diagnostics to expedite primary care for HIV and co-infections in vulnerable populations in Canada and internationally. She is developing innovative strategies of self testing for South Africa and Indian populations, a work supported by Grand Challenges Canada.

Dr. Pai, who holds a CIHR New Investigator Award, and is a recipient of the Rising Star Award in Global Health from Grand Challenges Canada, explained to R. Prasad by email the advantages of OraQuick.

Can you tell me briefly how OraQuick test works?

It is an antibody based test that that can be used in oral, and blood (whole blood, plasma and serum) samples. It detects antibodies developed within 1-3 months after getting infected. It cannot pick up acute or recent infection.

It detects oral mucosal transudate (OMT) — also called the crevicular fluid — collected in the space between the gum lining and the lips (inner space). OMT has a higher concentration of antibodies than saliva.

It is popular in the U.S., and has led to 85 per cent increase in uptake of testing in public health clinics where it was offered.

The oral version is popular because of its convenience, non invasiveness and reduced specimen contamination.

Oraquick is hailed as a major development, but it is only a screening test. Should the positive results not be confirmed by a blood test?

Yes, of course, because in a stigmatised disease like HIV, getting people to test is the hardest part. This is due to lack of privacy and loss of confidentiality and fear of visibility in public settings. So people desire private testing options. The over-the-counter OraQuick test is a historic milestone because it is a step towards destigmatisation of HIV and normalising an HIV diagnosis.

OraQuick is a screening test in that the first test result if performed after 3 months (window period) will need to be reconfirmed (if positive) with another blood-based test done in the lab.

If it is only a screening test and needs reconfirmation, how do you think the issues of stigma and discrimination get addressed?

Privacy — an OTC option offers privacy, avoids frequent visits to public health clinics! It is a proactive approach.

With conventional testing, statistics in the U.S., Canada and Europe suggest that 25-41 per cent of patients tested are lost in follow up.

Additionally, testing barriers (delay in receipt of test result, resulting anxiety of waiting and venipuncture) are seen as significant impediments to HIV test seeking.

But a person still needs to visit a doctor for treatment. So is the central issue of stigma and discrimination fully and really addressed?

The problem in the world today is that despite many things — availability of antiretroviral drugs in many parts of the world, the move towards an HIV cure, FDA approving Truvada as a pre- exposure prophylaxis oral pill to reduce HIV transmission — the reality is that a lot of people out there are living with undetected or undiagnosed HIV infection.

There is enough evidence that treatment of an HIV patient not only controls the infection, but also reduces the chances of passing the infection to their partner and reduces the disease burden of HIV in the community by reducing transmission.

But to get to treatment, we need to test people! About 7 out of 10 persons globally are living with undiagnosed HIV infection, and in the U.S. about 25 per cent of individuals do not wish to seek routine testing and do not test.

This is attributed to perceived stigma and discrimination, a low perception of risk for HIV, and the desire for fast and convenient testing options. Lack of convenience and privacy and fear of visibility are the other two reasons that deter acceptance of routine HIV testing.

Self-testing using rapid point-of-care testing circumvents these obstacles and has the potential for early detection and treatment of high-risk individuals.

Will it not be challenging to educate people on technical aspects like window period, low prevalence settings, expiry date of the test kit etc?

Conversely, the marginalized populations like commercial sex workers and injection drug users are very aware of these issues (like window period) as reflected in our rapid test studies conducted recently in Mumbai, India. These populations have access to free HIV testing. Yet in these populations there is a sizeable minority that do not seek to test. Those individuals can benefit from self-testing. The poor and illiterate will have trouble in comprehending it for sure. I have some doubts about reaching the really poor, and under resourced individuals. However, we need to study them before we make such assumptions.

At about $50 for the test kit, don't you think it is very expensive? More so, as this test actually needs such routine testing due to its low sensitivity level?

Yes it certainly is expensive. I think the price should be negotiated.

In our review, we found that individuals are willing to go up to $20, though I think that is high. I would think given that rapid tests are sold for 50 cents to $1, the test should cost around $5-10.

But we should first approve the test in the country. I have led two studies with OraQuick in India and it worked really well. I am surprised that to this day, the test is not approved in the country.

There is too much dependence on finger stick kits…we need to make a paradigm shift to offer choices!

Since the sensitivity is only around 93 per cent, will it not result in many true positives going undetected? How reliable is a test that does not have high sensitivity?

I did study the FDA data recently. The sensitivity of the test in the hands of lay users is 93 per cent. Part of the reason attributed to low sensitivity was due to the fact that patients had not sero-converted (when antibodies are developed) when they tested themselves.

This fact is important — individuals should be advised that, as in the case in pregnancy tests, some tests may fail to pick up infection within a 90-day period, so please get retested after 90 days.

If pregnancy tests could work in India, so can HIV. There is a huge global momentum in favour of self testing.

We have to weigh the risk of not detecting individuals with HIV against arguments of sensitivity. The benefits of screening people who have seroconverted far outweigh the risks to society.

Is the window period the only reason why the oral swab test turns in lower sensitivity results?

Also, the reaction of the oral fluid and binding of the reagent in the test is probably another reason. We need to educate individuals of co-morbid conditions, where you can get a false reactive test.

How serious is the issue of false negative test results?

Is the glass half full or half empty? I think it is half full…the bigger issue is getting people to test themselves. There is evidence from a meta-analyses that people who test themselves change their risk behaviour. This is probably applicable to the general population than very high risk taking populations.

Counselling is a part of testing in India. But there is no scope for such counselling in this case. Your comments.

No public health program or country will introduce self-tests without the option of pre and post-test counselling. That will never happen.

The difference is that innovative counselling techniques and tools will be offered — on phone. In the OTC version of the test that has been approved by FDA, a 24/7 call center has been set up to address the concerns of self-testers.