Pharmacogenetic Medince and Ethical Issues for Patients with HIV AIDS

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 particular gene variant? in the major histocompatibility complex (MHC), called HLA-B*5701, as being the key factor in hypersensitivity to abacavir. Individuals with the HLA-B*5701 allele were found to be more likely to have a hypersensitivity reaction to abacavir” (yourgenome.com, 2016). The HLA-B*5701 allele isn’t 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 trials have now shown that screening patients for HLA-B*5701 before treatment has dramatically reduced the number of side effects being experienced from abacavir use. In individuals found to have the HLA-B*5701 allele, 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 patient’s 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 wasn’t 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: it’s 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 brings up 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 that racial differences in the response to heart failure treatment are due to underlying pathophysiological differences between ethnic groups. However, there has been considerable criticism of this approach, based primarily on whether race or ethnicity can be used as adequate markers of genetic differences and that this decision provides support for the concept of race as a distinct biological marker, with a risk of genetic discrimination” (Brice & Sanderson 2006). While genetic difference among distinct racial and ethnic groups do exist, these differences do not align with the superficial factors often used to describe them (Brice & Sanderson 2006). The bulk of research out there had made it clear that genetic differences between branches on the ethnic tree are generally slighter than the deviations within these groups. Hence, categorization by skin color, race or ethnic group is a shoddy stand-in for determining common ancestry by concrete genetic markers (Brice & Sanderson 2006). More and more evidence based on a host of research studies, shows that variations in genes have comparable consequences across classically classified racial groups (Singer et al., 2004). Thus, ethnicity and race do not offer a consistent snapshot of genetic make-up and definitely should not be a main tool in the stratification of drug development. Last of all, when focusing on genetic origins for distinctive treatment response, this type of pharmacogenetics could overshadow relevant factors such as lifestyle and socioeconomic status (Brice & Sanderson 2006).

Furthermore, most professionals within the field of healthcare and medicine are aware of the fact that drug companies are not often the most decent and morally upright organizations doing business today. Thus with the increase of pharmacogenetics, such as the testing done for the drug abacavir, there are concerns connected to drug stratification and orphan drugs (Trusheim et al., 2007). Once drug companies know that they can stratify patients into specific treatment groups, solely based on their genes, could provoke these firms to redirect their focus in a manner, which is less than equal. Once genetic testing commences, it means that pharmaceutical companies have a way to get precise intelligence on how to direct their efforts. If drug companies want to, they can create drugs for one ethnic type over another, or for patients that are easier to treat than others. If these companies wish they can ignore those with rare genetic codes or with unusual illnesses—hence, making genetic testing in this arena an ethical concern. Still most experts argue that pharmaceutical companies have the biggest interest in making the most substances that can treat the highest amount of population sub-collectives (Brice & Sanderson 2006). Such a move would make the most economic sense. However, if one looks at the “orphan drug” phenomenon, one can see that circumstances just aren’t that simple. Orphan drugs are substances developed to provide treatment to people who have exceedingly atypical conditions that often stump doctors, and they are largely something that forces the medical community to find solutions to greater challenges (Shieappati et al., 2008). Legislation of the last few decades has intended to provoke more research into these substances, by incentivizing companies for exploring them and other alternatives. However, the problem is that many of these drug companies are primarily money motivated and such a niche market is viewed as both unattractive and unprofitable. Thus, it’s no surprise that “some have raised concerns that pharmacogenetics may exacerbate the orphan drug problem, where potentially valuable drugs are not developed because they would not have a large enough market, thus denying treatment to certain groups” (Brice & Sanderson 2006). The orphan drug issue is going to remain a pertinent one for the health board, medical practitioners and the entire medical community, as many scholars argue research into these issues raises the bar of care and science (Wästfelt et al., 2006)

Health insurance companies know that it is illegal for them to deny coverage based on genetic testing or the results from such tests. “Since 2008, with the passing of the Genetic Information Nondiscrimination Act (GINA), the federal government has barred health insurance companies from denying coverage to those with a gene mutation. But the law does not apply to life insurance companies, long-term care, or disability insurance. These companies can ask about health, family history of disease, or genetic information, and reject those that are deemed too risky” (Farr, 2016). This is an example of how organizations can be influenced by the results of genetic information, and how it can impact the level of care or protection received, and how these things can redirect the path that research and development takes.

Autonomy

One of the major ethical pillars connected to this issue is that patients always need to exercise as much autonomy as they would like (Vogenberg et al., 2010). For the pharmacogenetic procedure described in this paper, it seems so simple and so preventative, that one might as well undergo the test, just to be on the safe side and to check that one does not have a sensitivity to abacavir. However, this viewpoint fails to acknowledge that some people find genetic testing unattractive. Some people get very nervous have their genetic code looked at and find it a very invasive and intrusive procedure to undergo. Many people are worried about the results of any genetic test getting leaked to employers, the government or the general public, and are particularly concerned about an incidental findings that might come up during genetic testing (Wolk et al., 2013). For some people, undergoing any sort of genetic test is like taking a nude photo and hoping it doesn’t get leaked on the Internet: it is something they are definitely not comfortable with. When this is the case, it’s important that the autonomy of the patient is perfectly respected. Autonomy is a basic patient right and it asserts that all decisions need to be free of coercion and reflect the will and desires of the patient. Whether or not to have a genetic test might seem like a “no-brainer” in the situation of determining potential hypersensitivity to abacavir, but to some people it might violate deeply held religious beliefs—or it might simply violate specific values and predilections. Furthermore, when it comes to the genetic testing of children and adolescents, it brings up a host of controversy about who should be able to decide whether or not to go through with the testing—the minor or the adult? (Wertz et al., 1994).

The patient has the right to make an informed decision and the medical professional has a duty to help that patient make the most informed decision possible (Vogenberg et al., 2010). The healthcare professional has a duty to provide all relevant information, in a manner that is not intended to sway the patient in particular direction. This is important, because some healthcare professionals view it as being in their best interest if the patient does take the genetic test to determine if the HLA-B*5701 gene exists: it saves, time, heartache and money, and many view it as simple preventative and diagnostic test. Likewise, it’s important to prevent family members from attempting to sway the individual in any way, as certain relatives can exercise a strong influence over a person and are definitely something that can influence voluntary decision-making.

Privacy

Privacy is a relatively major issue for many individuals and signifies something that can have intricate and sometimes devastating consequences for patients, their family members and communities. During the frank discussion the patient has with the health care provider, there needs to be clarity given as to how the very sensitive nature of the information collected will be protected. Genetic information is more sensitive and intimate than one’s fingerprints. It is presumed that the data will be stored electronically and there needs to be a discussion about the security of the database and the people who have access to it. The clinician needs to be able to provide detailed and specific assurances about how the patient’s privacy will be preserved without a doubt (Ellis et al., 2001). This information needs to be safeguarded and after it is collected, the patient might want to know who technically owns it, who else will have access to it, and it what other ways it will be interpreted, and finally how the patient will be protected from harm should the information ever be leaked (Robertson et al., 2001). Genetic tests such as the one for the HLA-B*5701 gene can sometimes reveal more genetic information about the person than intended. This needs to be accounted for in the discussion between patient and healthcare provider.

Justice

Justice remains an ethical issue in any form of genetic testing or psychogenetics. One key aspect of justice would be the fair and equitable access to genetic testing to people of all backgrounds—of all races and socioeconomic classes. It remains to be seen if all people who have HIV/AIDS have access to this form of testing. Universal healthcare does not exist in America, and certain genetic tests aren’t necessarily covered by insurance.

Beneficial or Cavalier Allocation of Resources

One of the bigger the questions to examine in regards to this issue is whether or not pharmacogenetics represents a wise or cavalier allocation of resources. The resources available in health and medicine research and development is very scarce. Some experts believe that “the cost of developing pharmacogenetics is a misallocation of increasingly scare societal funds, particularly given other pressing global needs such as providing clean air and drinking water or preventing global famine and infectious diseases” (Barash, 2013). Yet the counter to this argument is obvious: pharmacogenetics represents a massive possibility for bettering the treatment, prevention and eventual annihilation of disease. More than half a million people die in hospitals each year from Adverse Drug Events (ADEs): these are expensive events that cost hospitals around $5.6 million per year (Barash, 2013). The costs connected with treating patients who require hospitalization as a result of ADEs ranges from $1.5 to $5.5 billion dollars each year (Barash, 2013). Most experts are of the opinion that the bulk of these reactions are connected to genetic variants and that so many of these adverse events can be avoided by testing people for ADEs before putting them on powerful drugs or drug cocktails (Grosse et al., 2006). Genetic testing with pharmacogenetic medicine offers much promise for the future and has significant clinical utility—though not everyone agrees.

Controversial Clinical Utility and Who Should Determine