Know HIV, no HIV

One of the biggest challenges in treating HIV/AIDS today is one that might be thought of as the simplest: diagnostics

Human Immunodeficiency Virus, or HIV, is an RNA virus that causes the devastating disease called Acquired Immunodeficiency Syndrome, or AIDS. The virus survives by injecting its own RNA sequence into the host cell and eventually, through a series of enzyme-facilitated processes, the nucleotide chain is converted into DNA and incorporated into the genome of the host cell. The virus then uses the host’s own cellular systems to reproduce and infect other healthy cells. The time it takes for the initial infection to become AIDS can be from two weeks to up to twenty years – or more – depending on the individual. During this period of latency, various opportunistic infections, cancers, and other conditions may develop.

HIV infection may occur in a variety of ways, with the most commonly known ones being unprotected sex, the sharing of needles, and from a mother to her child during pregnancy, childbirth, and breastfeeding.

The World Health Organization classifies the virus as a pandemic that infects about 2.5 million people per year, with an estimated total of 60 million individuals having been infected since its discovery. In 2008, over 2 million people died from AIDS-related causes. The disease has caused about 25 million deaths in history. While the infection rates appear to have stabilized in most developed areas of the world, prevalence is increasing in Central Asian and Eastern Europe. Sub-Saharan Africa remains the region with the highest infection rates and the largest HIV-positive population, accounting for 71 per cent of all new infections in 2008.

Shockingly, studies show that six out of ten HIV-positive individuals are unaware of their status, which is why frequent testing must be conducted in order to reduce the number of new infections. Unfortunately, many of the available test are costly and are infrequently available, especially in developing areas of the world.

Presently, there are two types of rapid HIV/AIDS testing systems, Point of Care (POC) tests – designed to deliver results rapidly and conveniently at a much lower cost than traditional tests – and self-tests – essentially POC tests, but even simpler. However, there are few FDA approved point-of-care (POC) tests and even fewer self-tests on the market. A recently published systematic review and meta-analysis study at McGill and Queen’s University, headed by Nitika Pai, a clinical epidemiologist at the McGill University Heath Centre, looks at the effectiveness of the POC antibody test OraQuick Advance HIV-1/2, manufactured by OraSure Technologies in Pennsylvania.

The study, published in The Lancet Infectious Diseases on January 24, compares the diagnostic accuracy of OraQuick, and investigates how the results may be applied to sub-Saharan African to help in eventually reducing the number of new infections.

“Although previous studies have shown that the oral fluid-based OraQuick Advance HIV-1/2 test has great promise, [McGill’s] is the first to evaluate its potential at a global level,” states Pai. The test itself is a simple white stick with a flat swab at the end, and is administered in a swipe around the mouth between the gums and the lips. The swab end is then placed in a buffer solution, and results are produced after around twenty minutes.

The study shows a 99 per cent accuracy in diagnosis for high-risk populations, and a 98 per cent accuracy in low-risk ones. It has been found that in the 1 to 2 per cent error margin, more false-positives are produced than false-negatives, which many argue is better than the alternative.

Even with this high level of accuracy, researchers like Rosanna Peeling, coauthor of the study from the London School of Hygiene and Topical Medicine, strongly recommend a professional follow-up after self-testing.

By making a rapid POC test readily available, Pai hopes to “bring an end to the stigmatization associated with HIV testing.” As part of her research, Pai has developed an innovative self testing strategy to be implemented in Africa, which is expected to make OraQuick more available, reduce visibility, increase privacy, and eliminate discrimination.

The strategy is presently being evaluated in a small sample of healthcare workers at the University of the Witwatersrand in Johannesburg and at the University of Cape Town, both in South Africa.

A downside to the twenty-minute OraQuick stick is that it only looks for the presence of antibodies, which can leave a window of one to three months between infection and the immune response where antibodies are produced. Peeling suggests that this should be kept in mind when interpreting the result of a test. The current cost for one OraQuick test is $10.

To reduce the window of inaccuracy, Pai is currently working on another POC HIV test called Alere Determine HIV 1/2 Ag/Ab, manufactured by Alere, which tests for both antigens and antibodies. This test successfully reduces the inaccuracy window down to two weeks from OraQuick’s three months. Pai is also researching another POC test which can simultaneous detect HIV, Hepatitis B and C, and syphilis. The multiplex test takes only 15 minutes to complete and costs around $4.

By increasing the availability of POC or self-HIV tests, Pai stresses that “HIV today is not a death sentence. There are cheaper, fast acting drugs available that can prolong the life of an individual, provided you are diagnosed early and treated early.”

To further test OraQuick, Pai has paired up with Pierre-Paul Tellier, director of McGill Student Health Services, to test out OraQuick amongst students. According to Pai, this is the first HIV self-testing study in the world being conducted on an educated population. This new venture will allow researchers to test the accuracy of OraQuick (originally made for POC) when used in a self-testing setting. The results are expected to pave the way for better-designed self-tests. Currently, Pai and Tellier have recruited over 125 McGill students for the study, and are still looking for more.

Today, OraQuick Advance HIV-1/2 is a POC test only available for administration in clinics by health care professionals. However, OraSure Technologies has already submitted a very similar self-test to the FDA, and Pai expects its approval sometime this year.