Pharmacogenetic Medince and Ethical Issues: Testing for HLA-B*

Pharmacogenetics revolves around a pre-determined range in how individuals react to certain drugs, in regards to both their beneficial and adverse results. This concept had emerged when tasters and non-tasters of phenylthiocarbamide (PTC) had been identified, and the ability to feel that taste was shown to be inherited (Luzzatto & Seneca, 2014). Since screening individuals for PTC tasting turned out to be simple and barely invasive, PTC became one of the initial traits that was examined at length at the dawn of human population genetics. Since then, the field of pharmacogenomics medicine has evolved exponentially, giving scientists valuable data that has given them a more compelling road map in their treatment plans than never before.

One arena where this type of work is largely instrumental is in the field of genetic testing for those suffering from HIV/AIDS and has functioned as an aspect of science, which furthered the understanding of the condition (Hu et al., 19960. Much HIV medicine is newer to the market and often has side effects, some of which can be very unpleasant for the patient. The most prominent example of this is the drug abacavir, a drug used with other antiretrovirals in order to treat HIV infection. While Abacavir is known to be extremely successful in treating HIV, the virus that is responsible for AIDS, a small percentage of patient do suffer side effects, such as rash, extreme tiredness, and diarrhea. Based on these reactions, scientists concluded that some patients had a hypersensitivity to the drug, based on their unique systems and make-up (Rauch et al., 2006). Essentially, their immune systems were producing an exaggerated reaction to the drug, one that was almost akin to an allergic reaction. Based on these findings, it appeared as though the genes, which were in charge of controlling the overall response of the immune system, were most likely why the individuals were having these particular side effects. The scientists theory turned out to be correct. In 2002, two groups identified a particulargene variant?in the major histocompatibility complex (MHC), calledHLA-B*5701, as being the key factor in hypersensitivity to abacavir. Individuals with theHLA-B*5701allele were found to be more likely to have a hypersensitivity reaction to abacavir (yourgenome.com, 2016). TheHLA-B*5701allele isnt terribly common, but its appearance is significant: it occurs at a frequency of around five percent in people from Europe, one percent in people of Asian descent and less than one percent in those of African descent (yourgenome.com, 2016). Clinical trialshave now shown that screening patients forHLA-B*5701before treatment has dramatically reduced the number of side effects being experienced from abacavir use. In individuals found to have theHLA-B*5701allele, abacavir is avoided, and alternative HIV treatments are given (yourgenome.com, 2016). This form of testing allows clinicians to avoid giving patients a substance that they know might cause nasty side effects, based on the patients genetic make up and many clinicians view it as necessary genetic screening (Laonge et al., 2010).

While the test is very cost effective and ends up saving the medical community money in the long run, there was initial concern that it wasnt completely accurate for all ethnic types. Years ago, there had been concerns that such tests demonstrated less accuracy in African Americans than in Caucasians (Saag, 2008). Hence, a research study was commenced in order to shed light upon this exact issue, and it was discovered without ambiguity that this test, the one which determine who is likely to develop a severe allergic reaction to abacavir boasts the same level of accuracy among both whites and blacks (Saag et al., 2008). This study found that each black and white participants who had physical manifestations which indicated a possible hypersensitivity to abacavir had these signs confirmed via a skin patch test which demonstrated a positive HLA-B*5701 test (Saag et al., 2008). Making this determination was important because physical manifestations, which indicate an allergy to abacavir, can also be connected to other anti-HIV drugs, and other clinical trials have demonstrated a large number of patients who were not taking abacavir were diagnosed with having a biological aversion to the substance (Saag et al., 2008). Thus, it was important to engage in this retrospective study in order to determine the efficiency of this exact test in patients of different ethnicities, using two groups. Patients in the first group all developed symptoms of an abacavir hypersensitivity reaction and had a skin-patch test to check for an allergic reaction to abacavir. This test exposes the skin to a small amount of abacavir to see if it provokes a reaction. Patients with a negative skin-patch test were diagnosed as having a clinically suspected hypersensitivity reaction, and those with a positive skin-patch test as having an immunologically confirmed hypersensitivity reaction (Carter, 2008). At this point, the participants were connected with a second collection of participants that were made up of people who had been treated by abacavir, but who had not developed symptoms of an allergic reaction to the substance (Saag, et al., 2008). Hence, blood samples had to be taken from each participant in order to determine whether the HLA-B*5701 gene was present. The participants of both races, black and white, that boasted a positive skin patch test, known as a reaction which implied extreme sensitivity to abacavir, all had positive HLA-B*5701 test, denoting complete sensitivity to the substance. While these results were not uniform throughout the study, they did demonstrate that the effectiveness of the HLA-B*5701 test was 96% in black patients and 99% in white patients (Saag et al., 2008). This leads investigators to aptly conclude that the mere existence of HLA-B*5701 is meaningfully connected with a biological aversion to abacavir; these findings also demonstrate that the HLA-B*5701 screening has a high level of generalizability and can be used with great success, regardless of race (Saag et al., 2008).

Ethical Issues

This type of testing might appear to be very simple: its designed to determine whether or not the individual contains a gene, which will cause them sensitivity to the substance, and provide unwanted side effects. In order to be certain that one does not have to deal with unwanted side effects, genetic testing for the HLA-B*5701 is ideal. However, it bringsup innate ethical concerns for all participants involved in the pharmacogenomic process. One of the major concerns connected with this genetic testing is that for this particular drug, abacavir, there are ethnic patterns to the hypersensitivity, with deviations between whites and ethnic minorities. being of African descent were associated with a nearly 40% reduction in the risk of hypersensitivity. In a study of 540 patients that included a predominance of ethnic and racial minorities, Hispanic ethnicity was associated with an OR of 2.77 when compared with other ethnic backgrounds. Patients of white race were found to be at significantly greater risk in another study of a population with a low percentage of ethnic minorities (Hewitt, 2002). The ethical issues that findings like this provoke is that when certain drugs are found to be more predisposed to one ethnic group over another, such differentiations can influence pharmaceutical companies. This is something that occurred with the marketing of BiDiL for the treatment of cardiac collapse in African Americans (Brice & Sanderson 2006). This was dubbed by insiders as the first ethnic drug as it was greenlit for use by one particular ethnic group. The US company NitroMed has claimed...

…thrombosis and embolism (Barash, 2013). As beneficial as Warfarin is, it does have a hand in causing ADEs. Roughly one third of patients receiving Warfarin carry variants in two genesCYP2C9 and VKORC1that put them at high risk of bleeding if given the standard dose. On August 16, 2007, the FDA cleared a genetic test for Warfarin sensitivity and updated Warfarins original labeling to say that variations in CYP2C9 and VKCOR1 can affect optimal dosing (Barash, 2013). This is a clear example of how theres still a lot to discover about the field of pharmacogenetics and how to medicate properly with this genetic information. Thus, foundational pillars need to be in place, such as how to appropriately deal with this sensitive genetic testing. These foundational pillars also include the best way to address so many of these ethical issues and to have open channels of communication.

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