Tuesday, December 1, 2015

World AIDS Day and how to science.

Part of learning “to science” is comparing popular media coverage of original research to the original research itself. This critical thinking exercise is extremely important, but hard to practice without a solid footing in research methods and how science is supposed to work. If you have a hobby-level interest in following science, consider taking one of those free online courses about research methods. It will help you to better understand new breakthroughs, controversial topics (eg. the vaccination debate), and government recommendations.


Inspired by a social media post by the Centers for Disease Control regarding news media spreading misinformation about their recently released data, in addition to World AIDS Day, here is one such paper I submitted in 2012. It has some interesting info on newer HIV research. Perhaps you will find it interesting, perhaps you won’t.  

Comparison of media to scientific data. Plus, bonus information on HIV/AIDS treatment breakthroughs.


Section 1: Media Article Summary

 Bardi, a writer for The University of California- San Francisco website, published an article detailing original research conducted at The University’s affiliate hospital, San Fransisco Veteran’s Memorial Hospital.  The article, titled Fighting Infections: Old Drug Reveals New Tricks and can be read on the University of California-San Fransisco website. The article opens with a short history on the use of interferon as a drug therapy. Interferon is useful in alleviating the symptoms of Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS)  (Bardi, 2012). It was, therefore, prescribed to HIV patients in the 1980s.  For the past 25 years, the reason interferon relieves HIV symptoms has remained a mystery. As a result, researchers stopped studying interferon as an antiretroviral and began researching other antiretroviral agents. These other antiretroviral agents have a mechanism of action that is clearly understood. However, due to a better understanding of immunobiology, researchers at the San Fransisco Affiliate Hospital have begun studying the mechanism of action for interferon again after two decades. A recent study addresses why in vivo interferon treatment is effective in relieving HIV symptoms.
The 2011 Pillai et al. study observed 20[mas1]  participants in the Swiss HIV Cohort Study. These participants treated both their HIV and diagnosed Hepatitis C (HCV) iinterferon. They were not taking any antiretroviral drugs to treat their HIV. This gave researchers a clear view of how interferon might affect HIV levels.
The study found that interferon increases the effectiveness of restriction factors. Restriction factors are a part of the immune system that act at[mas2]  an intrecellular level. Interferon is a hormone found naturally in host cells which aides in immune response. Antiviral doses of interferon have been shown to increase the effectiveness of the restriction factors APOBEC3[mas3]  and tetherine. APOBEC3 mutates virus particles. These mutations make it impossible for the virus to replicate in other host cells. Tetherine binds to virus particles while maintaining a bond with the host cell. This prevents the virus from invading new cells.
HIV produces two proteins that counter these restriction factors.  The protein, Vpu, acts against tetherin while another protein, Vif, fights APOBEC3. Despite the ability of HIV to fight restriction factors, doses of interferon used to treat HCV effectively lowered HIV levels in patients. This is a major first step in HIV treatment but is far from final.

Section 2:  Scientific Article Summary
             Pillai et al. in conjunction with the Swiss HIV Cohort study investigated why cytokine interferon-alpha (INF-α) is an effective antiviral in their 2011 study. This study was funded by The National Institute of Health and an American Recovery Act supplemental grant. Researchers gathered longitudinal data from a group of HIV/HCV infected participants.  The study plotted data of the HIV viral load in the participant’s blood plasma prior to, during, and post treatment. After analysis, researchers found that plasma viral levels dropped -0.921 log 10 copies/ml while the participant was taking INF-α. Plotting of shifts in CD4+ count showed no correlation between the drop in viral plasma load and a drop in CD4+. This is significant because it suggests that the drop in plasma viral load was probably due to increased restriction factors, rather than an immune response at a multicellular level.  This data is congruent with previous data, suggesting that INF-α prevents viremia, the passage of virus particles in to the blood stream. Prevention of viremia occurs at the cellular level due to restriction factors.
            Three restriction factors are present in the immune response to primate immunodeficiency viruses: apolipoprotein B mRNA editing enzyme, catalytic peptide 3 (APOBEC3), bone marrow stromal cell antigen 2 (BST-2/ tetherine), and Trim5α. In humans trim5α does not inhibit immunodeficiency viruses, however ,APOBEC3 has a profound effect. APOBEC3 protein induces a shift from cytosine to uracil during mRNA synthesis, causing the DNA to be replicated with adenine where guanine should be. This mutation prevents the virus from reproducing. Similarly, BST-2 is a transmembrane protein channel found on the lipid bilayer of cells. As the virons attempt to exit the cell, the BST-2 bonds to them while remaining bonded to the cell membrane, effectively trapping virus particles in the host cell. 
            The HIV evolved defenses to counteract these restriction factors. It uses 16-kDa viral protein U (Vpu) to counteract the BST-2 response. Vpu removes the BST-2 from the lipid bilayer. The decrease in BST-2 allows more virions to escape the host cell. HIV has also evolved a defense mechanism against APOBEC3. 23-kDa protein virion infectivity factor (Vif) destroys APOBEC3[mas4] .
Section 3: Critical Analysis
            The media article is written for leisure reading. It is a summary of a complicated research study.  Therefore, the audience for this article would include adults with an interest in health science. The majority of the audience probably does not have a vast knowledge of virology and immunology.  The media article effectively summarized the scientific article and can be used by an audience with limited scientific knowledge.
            Bardi did not make any claims beyond the original research; therefore, a novice reader could use this article to aid in the understanding of the original research. Or, since the article is quite accurate, a leisure reader can believe all the claims made in the media article, instead of having to consult the original research. Finally, the media article can be used to educate HIV/AIDS patients, in a quick and concise format, on a new treatment option.  
            The media article did not include information on the shortcomings of the study. For example, 20 participants is a very limited sample size.  Larger studies are generally more accurate. Also, an ideal study would examine how interferon works in patients who do not also have HVC. Without a discussion of the shortcomings of a study, the information can be misleading. Since this article is written for an audience without a vast scientific knowledge, it can be assumed that some of the readers may not know how to preform research These readers may not realize that 20 subjects is typically a pilot study and that more research should be done before any theories are created.   
Section 4: Applications
            Currently, there are few effective antivirals on the market. The antivirals we do have typically slightly decrease the duration and severity of the viral infection (CDC.Gov, 2012). A very important application for this data set is the development of a more effective antiviral. The mechanism of action for interferon can be applied to many other viruses.   A shorter duration of viral illness decreases the infectivity rate of the illness. Doctors and public health officials could use interferon to slow the spread of viral epidemics, including influenza. In an era where so many citizens are afraid to get vaccinated, public health officials will have to find other means of preventing disease transmission. Antivirals may be the key to supplementing the low vaccination rate.
While interferon cannot cure long-term viruses, like HIV,HCV, or herpes, it can drop the viral load to a low enough level that the patient no longer experience symptoms. Furthermore, a low viral load decreases the chances of spreading the virus. For example, if the blood viral load of HIV is low there is a decreased probability that the patient’s sexual partner will be exposed to the virus (Anema, Wood, & Montaner ,2008).
Public health officials can use interferon on both an epidemiological scale and a personal scale.  In the case of HIV and HCV, interferon can be used to decrease the rate of new infections. The ideal plan to decrease the infection rate would include three components: 1.education regarding HIV and HCV. 2.services for HIV and HCV infected individuals including needle exchanges and free condoms. 3 antiretroviral treatments capable of dropping the viral load below the rate that is high enough to spread the virus.
A drop in my viral load is associated with a decrease in symptoms. Therefore, interferon can be used to improve personal wellness by dropping the patient’s viral load. There are several antiretroviral treatments that drop the patient’s viral load already on the market. However, the HIV is constantly evolving defense mechanisms against antiretroviral treatments; therefore, we need a wide range of antiretroviral agents. Furthermore, the combination of several antiretroviral drugs is capable of decreasing the viral load further than if the patient uses only one drug at a time. Understanding how interferon works will make combining the drug with other drugs safer.  The addition of interferon to our arsenal of antiretroviral drugs is a public health break through.
Of course, all of these applications are only viable with more research on interferon. The Pillia et al. study was a great pilot study. Perhaps, with further study the researchers will find a way to combine interferon with a drug that inhibits Vpu and Vif. This combination would further increase the effectiveness of the restriction factors, APOBEC3 and BST-2. I am optimistic for the future of interferon.

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