IN/VISIBLE: A Systemic Analysis of HIV/AIDS, COVID-19, and Endocrine Disrupting Chemicals in Society by Sarah Sullivan

IN/VISIBLE A SYSTEMIC ANALYSIS OF HIV/AIDS, COVID-19, AND ENDOCRINE DISRUPTING CHEMICALS IN SCIENCE & SOCIETY

BY DRAKE HIPE, MIKE MATTHEWS, SHEEL SHAH, EDWARD SUAREZ, AND SARAH SULLIVAN SOCIETY & GENETICS 108: FALL 2020

land acknowledgement As a land grant institution, the students of Society & Genetics 108 at UCLA acknowledge the Gabrielino/ Tongva peoples as the traditional land caretakers of Tovaangar (Los Angeles basin, So. Channel Islands).

ACT UP NY, 1991

letter from the authors

As the COVID-19 pandemic and ongoing strides for racial justice have recently taught us, examining the diverse factors that influence health has never been more important — while factors such as history and social determinants may manifest in disproportionate health outcomes for marginalized communities, they can also accumulate over time, resulting in disproportionate risks for such communities. The ongoing HIV/AIDS epidemic, COVID-19 pandemic, and health crisis involving exposure to EDCs are gleaming manifestations of this phenomenon – their impacts unequally affect certain individuals and stress the need for intersectional change and advocacy. As people not living with HIV, we, as authors, recognize that we are adopting an external perspective to the AIDS epidemic and the social determinants that create an unequal health burden for those affected by HIV/ AIDS. Our goal is to present unbiased reporting of facts and data in regards to HIV/AIDS, COVID-19 and the effects of exposure to EDCs to draw conclusions about the overlapping effects of these diseases and the social institutions that shape them. Both the individual privileges and oppressions we are awarded inherently shape our perceptions of and perspectives on each of these health crises, and we actively seek to deconstruct unconscious stigma in our own research and writing. Specifically, we aim to show that EDCs, COVID-19, and HIV/AIDS are inextricably linked. Exposure to EDCs from an early age has been implicated in changes to respiratory health, endocrine system function, and immune system function. Moreover, based on current data respiratory distress and decreased immune system function are known to exacerbate the symptomatology associated with COVID-19. Similarly, the very treatments that are used to combat HIV/AIDs— antiretroviral therapy—have been linked to downstream changes in endocrine system function, ranging from hormonal dysregulation to metabolic changes that could potentially predispose individuals to more severe cases of COVID-19. At the same time all of these health conditions are unequally distributed throughout the population and influenced by a variety of social and historical determinants. Through this project we hope to illuminate these determinants and highlight the need for interdisciplinary approaches to addressing these ongoing issues. There are currently no cures for COVID-19, HIV/AIDS, or ailments due to EDC exposure. However, understanding the roots of disproportionate health outcomes and addressing them through an interdisciplinary lens can help reduce the health disparity gap, specifically within marginalized communities. Through analysis of the intersectionality between HIV/ AIDS, COVID-19, and EDCs, we hope this knowledge can shed light on flaws within our society and illuminate innovative solutions and effective policies as we continue to forge a path forward. Drake Hipe, Mike Matthews, Sheel Shah, Edward Suarez, and Sarah Sullivan

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in/visible illnesses

table of contents 03

classification of terms

you should say this, not that

history 05 social context through poetry

05 07

dealing with unprecedence

a brief timeline of events

biology 13 15

the endocrine system and disruptors

hiv: stages of infection, prophylaxis and treatment, and endocrine effects

biology of covid-19 and why some are more affected than others

diabetes: a biological link between edcs, hiv/aids, and covid-19

an introduction to viruses

ivan sull ah sar

25 28 31

by art

social determinants bearing an unequal burden economics and inequities hiv: activism, drugs, and evolved understandings

concluding remarks

original cover art by sarah sullivan

classification of terms by sarah sullivan

HIV/AIDS

HIV: human immunodeficiency virus HIV is a virus that attacks human immune cells that fight off infections.

PEP: post-exposure prophylaxis PEP is an antiretroviral medication taken after exposure to HIV in order to prevent contraction of the virus.

AIDS: acquired immunodeficiency syndrome AIDS refers to the latest stage of HIV infection in which an individualâ&#x20AC;&#x2122;s count of CD4 cells (a white blood cell of the immune system) falls below 200 cells per cubic millimeter of blood or if they develop an opportunistic infection.

U = U: undetectable = untransmittable If a person living with HIV using ARTs maintains an undetectable viral load they are unable to transmit HIV to their sexual partners.

ART: antiretroviral therapy Treatment that uses antiretroviral (ARV) medications to suppress the viral load of HIV within the body to reduce symptoms of the virus, restore immune function, prevent progression of the virus, and prevent transmission of HIV.

MSM: men who have sex with men Any male-identifying individual who engages in sexual activity with other self-identified men. This term avoids identity labels and only specifies sexual activity, not sexual orientation, and is used from a public health standpoint to identify members of the population who may engage in same-sex sexual activity while not identifying as queer, gay, bisexual, or LGBTQ+.

PrEP: pre-exposure prophylaxis PrEP is an antiretroviral medication people not living with HIV can take in order to reduce their risk of contraction if they are exposed to the virus.

STD/STI: sexually transmitted disease/infection Any disease or infection that can be passed from one person to another via sexual contact. However, not all STDs or STIs are only transmitted via sexual activity.

COVID

COVID-19: coronavirus disease 2019 An infectious respiratory disease caused by the coronavirus SARS-CoV-2. Stands for corona virus disease 2019, the year which it was discovered. SARS-CoV-2: severe acute respiratory syndrome coronavirus 2 The specific virus that causes COVID-19, part of a larger family of viruses called coronaviruses. coronavirus: A group of RNA viruses that cause respiratory illnesses, named for their distinct crown-like spikes of glycoproteins on their surface.

EDCs

EDC: endocrine disrupting chemicals Chemicals or groups of chemicals found in the environment that alter the function of the bodyâ&#x20AC;&#x2122;s hormones. BPAs: bisphenol A

DDT: dichlorodiphenyltrichloroethane PAH: polyaromatic hydrocarbon PCB: polychlorinated biphenyl A nurse conducts a drive-thru COVID test in New York. Brendan McDermind, 2020

SOURCES: HIV.gov. (2020, June 05). What Are HIV and AIDS?. https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/what-are-hiv-and-aids Centers for Disease Control and Prevention. (2019, October 30). HIV: Terms, Definitions, and Calculations. https://www.cdc.gov/hiv/statistics/surveillance/terms.html National Institutes of Health. (2017, October 23). Sexually Transmitted Diseases. MedlinePlus. https://medlineplus.gov/sexuallytransmitteddiseases.html The University of Virginia. (2020, October 2). Coronavirus & COVID-19: Glossary of Terms. UVAHealth. https://uvahealth.com/services/covid19-glossary

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YOU SHOULD

SAY THIS NOT THAT

A SHORT GUIDE ON LANGUAGE AROUND HIV/AIDS. B Y S A R A H S U L L I VA N

Los Angeles Public Library, 1989

Language has played a significant role in perpetuating stigma surrounding HIV/AIDS, particularly though its use of deprecating language to describe individuals and populations living with or at risk of HIV. Below are a few terms that should be used to avoid potentially harmful language.

PERSON INFECTED WITH HIV/AIDS

PERSON LIVING WITH HIV/AIDS, AN HIV-POSITIVE PERSON

It is important to use “people-first language” when discussing an individual’s health status because it focuses on the person, not their illness or disability. This maintains autonomy and avoids victimization or vilification of the individual.

TO CATCH HIV/AIDS, TO BE INFECTED WITH HIV/AIDS

TO ACQUIRE HIV, TO BE DIAGNOSED WITH HIV

T he verbs infect, spread, or pass infers judgement on an individual living with HIV as someone who is dangerous in the general population due to their positive status or as someone who may intentionally perpetuate the transmission of HIV.

BODILY FLUIDS

FLUID OF TRANSMISSION (BLOOD, SEMEN, PRE-EJACULATE, VAGINAL FLUIDS, RECTAL FLUIDS, BREAST MILK)

Using the term “bodily fluids” without specifying that it is a fluid that transmits HIV perpetuates the idea that all bodily fluids can transmit HIV when in reality, many (such as saliva, sweat, or urine) cannot. This misinformation has spread fear of contact with and discrimination against individuals living with HIV.

DIED OF AIDS

DIED OF AIDS-RELATED COMPLICATIONS, DIED OF AIDS-RELATED ILLNESSES

It is impossible to “die of AIDS.” HIV weakens the immune system and makes it susceptible to further life-threatening illnesses or infections, but AIDS is never the sole cause of death in a person living with HIV/AIDS.

FULL-BLOWN AIDS

JUST AIDS OR LATE-STAGE HIV

There is no such thing as “full-blown AIDS” – there is only Stage 3 HIV, referred to as AIDS, when an individual living with HIV’s CD4 count drops below 200 cells/mm3.

SOURCES: Centers for Disease Control and Prevention. (2020, July 30). A Guide to Talking About HIV. Stop HIV Together. https://www.cdc.gov/stophivtogether/library/stop-hiv-stigma/fact-sheets/ cdc-lsht-stigma-factsheet-language-guide.pdf

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in/visible illnesses: history

A BRIEF TIMELINE OF EVENTS BY EDWARD SUAREZ

HIV/AIDS Epidemic: 1981: First reported case of what we will come to know as HIV/AIDS among gay men and people who injected drugs.

1983: CDC identified all major routes of transmission, and the following year, the cause of the virus was found to be HTLV-III/LAV.

1987: FDA approves the first anti-retroviral drug to treat HIV, called AZT. In the same year, WHO launches the Global Program on AIDS to raise awareness and provide research and treatment assistance.

1990: Americans with Disabilities Act (ADA) established, granting some protection from discrimination for those living with HIV.

1995: FDA approves highly active antiretroviral treatment (HAART), which brought deaths related to HIV/AIDS to a 60-80%

1996: UNAIDS was established to bring awareness and advocacy to a global stage; called for a coordinated response across the United Nations.

Endocrine Disrupting Chemicals: 1923: Pharmaceutical research develops the first bioassay, which measures the effects of a substance on living cells and tissues.

1962: Rachel Carson published Silent Spring, which created a link between reproductive health issues and chemical exposures in nature, specifically with DDT.

COVID-19: December 2019: Wuhan, China officials confirm dozens of cases of pneumonia; we will come to know these as the first cases of COVID-19.

1971: Diethylstilbestrol (DES) approved for at-risk women to prevent miscarriages, which was later revoked by the FDA after it was associated with vaginal cancer in daughters of young-adult who were exposed during gestation.

1996: US Food Quality Protection Act and amendments to Safe Drinking Water Act passed in an effort to identify endocrine disrupting chemicals. EPA eventually develops the Endocrine Disrupting Screening Program (EDSP) which places emphasis on science and risk in screening for potential EDCâ&#x20AC;&#x2122;s.

March 2020: Researchers administer the first shot in a clinical trial of a COVID-19 vaccine March 15: CDC releases guidelines that recommended the cancellation of any events with more than 50 people. March 18: US closes its borders to all travel considered nonessential to the US. March 18: Trump signs Family First, Coronavirus Response Act which provided unemployment and food aid.

April 2020: Donald Trump halts funding of 400 million USD to the World Health Organization. By now, about 95% of all Americans are under lockdown.

1998: Organization for Economic Co-operation and Development (OECD), a partnership between Japanese and U.S. governments, established to promote screening and testing of EDCâ&#x20AC;&#x2122;s.

May 2020: Several countries who had successful containment, like New Zealand and Thailand, began easing lockdown restrictions; COVID cases spike in Brazil.

March 27: Stimulus Bill passes.

SOURCES: A Timeline of COVID-19 Developments in 2020. (n.d.). Retrieved December 01, 2020, from https://www.ajmc.com/view/a-timeline-of-covid19-developments-in-2020 Endocrine Timeline: Enhancing Scientific Understanding. (2017, December 14). Retrieved December 01, 2020, from https://www.endocrinescience.org/endocrine-timeline-near ly-100-years-enhancing-scientific-understanding/

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These three timelines focus on the United States’ governmental and scientific response to each event. Each timeline highlights key measures adopted to combat its specific public health crisis as well as the progression of scientific intervention in order to portray the competence, or lack thereof, of the response. These timelines provide a foundation for assessing the response as either sufficient or lacking, especially when looking at these public health crisis as spanning over a period of time to visualize the speed and urgency of government action.

2001: United Nations established a global fund to minimize virus spread via prevention, treatment, and buying medication. First round of funding resulted in 600 million USD.

2003: President Bush announced the United States President’s Emergency Plan For AIDS Relief (PEPFAR), a 5 year-plan with 15 billion USD in funding to address AIDS in countries with most cases of AIDS.

2002: Various international organizations come together to publish the State of the Science Report on Endocrine Disrupting Chemicals, which details a definition of EDC’s, claims the existence of EDC’s, but concludes that there is insufficient evidence to establish EDC’s as harmful to human health.

August 2020: CDC updated guidelines for testing but reverses itself later on.

September 2020: US rejects partnering with WHO in a global effort to create a vaccine.

2010: A travel ban that banned HIV-positive individuals from traveling to the United States was lifted.

2009: U.S. EPA’s Endocrine Disruptor Screening Program mandates test orders for manufacturers of EDSPs list 1 chemicals, which included 67 pesticides or high volume pesticide inserts.

An interdisciplinary lens highlights parallels between each health crises, which will be discussed later on. Because these events share key traits, comparing actions that have tangible influence on public health can grant insight on which modes of actions can optimize these outcomes. Furthermore, the history of EDC’s is comparably less developed, so the timelines of HIV/AIDS Epidemic and COVID-19 Pandemic can provide a reliable method of predicting the course of EDC and its effects on public health based on government and scientific responses.

2012: FDA approves PrEP as a preventitive measure.

2013: US EPA suggests that EDSP list 2 chemicals should be screened with tier 1 assays.

October 2020: Trump and First Lady both test positive for COVID-19, Trump is admitted to a hospital. October 5: Trump leaves hospital and receives some treatment at home. October 22: Remdesivir is the first drug approved by the FDA for COVID-19 treatment.

2014: UNAIDS establishes “fast track” program to dramatically ramp up efforts to end the epidemic by 2030.

2017: U=U, undetectable = untransmittable was a slogan adopted to destigmatize HIV/ AIDS.

2015: EPA makes progress with EDSPs with the results of the screening tests of 52 list 1 chemicals published. EPA announces a shift in methodology to maximize efficiency and minimize the amount of laboratory animals used.

November 2020: President-elect Biden publishes his COVID-19 plan as part of his transition into presidency; Pfizer publishes vaccine results with 90% efficacy. November 16: Moderna also publishes its results, revealing that its vaccine had a 94.5% efficacy

SOURCES (CONTINUED): History of HIV and AIDS overview. (2019, October 10). Retrieved December 01, 2020, from https://www.avert.org/professionals/history-hiv-aids/overview Muccari, R., Chow, D., &amp; Murphy, J. (2020, November 30). Coronavirus timeline: Tracking the critical moments of Covid-19. Retrieved December 01, 2020, from https://www.nbcnews. com/health/health-news/coronavirus-timeline-tracking-critical-moments-covid-19-n1154341 Susie Neilson, A. (2020, September 29). A comprehensive timeline of the coronavirus pandemic at 9 months, from China’s first case to the present. Retrieved December 01, 2020, from https://www.businessinsider.com/coronavirus-pandemic-timeline-history-ma jor-events-2020-3

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in/visible illnesses: history

social context through poetry by edward suarez

Portraying societal perspectives of those most affected by public health crises – what were the predominant attitudes that surrounded these major events?

In the Time of Plague by N. Scott Momaday, 2020 We keep indoors. When we dare to venture out We are cautious. Our neighbors Smile, but in their eyes there is Reserve and suspicion. They keep their distance, As we do ours, in mute accord. Much of our fear is unspoken, For there is at last the weight of custom, The tender of rote consolation. We endure thoughts of demise And measure the distance of death. Death too wears a mask. But consider, there may well be good In our misfortune if we can find it. It is Hidden in the darkness of our fear. But discover it and see that it is hope And more; it is the gift of opportunity. We have the rare chance to prevail, To pose a resolution for world renewal. We can be better than we have ever been. We can improve the human condition. We can imagine, then strive to realize, Our potential for goodness and morality. We can overcome pestilence, war and poverty. We can preserve our sacred purpose. We can Determine who we are in our essential nature And who we can be. We are committed to this end For our own sake and for the sake of those Who will come after us. There is a better future, And we can secure it. Let us take up the task, and Let us be worthy of our best destiny.

Activist group ACT UP staged many protests in Los Angeles through the 1990s. Silence = Death, 1989

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A protestor uses a plague mask to protest wearing facial coverings. Getty Images, 2020

IN THE TIME OF PLAGUE N. Scott Momaday is a writer, poet, and novelist who won the 1969 Pulitzer Prize for fiction for “House Made of Dawn.” His poem is an optimistic view of humanity emerging victorious from the pandemic (Coronavirus Poems, 2020). In the Time of Plague fittingly compares COVID-19 with the Plague in how widespread COVID-19 has become. The first half of the poem takes on a more defeated tone as individuals are described to “keep indoors,” remain “cautious,” and “keep their distance.” Attitudes towards social distancing and wearing masks, practices known to minimize the spread of the coronavirus, is personified through death; the author claims that “Death too wears a mask,” and people are left to “measure the distance of death” and “endure [the] thoughts of demise.” The beginning of the poem depicts the prevailing mindset that most individuals living in the era faced: finding the balance between laxed social distancing for the sake of mental health and the possibility of contracting the virus. The second half takes on a more optimistic tone as the author contemplates, “we can improve the human condition... strive to realize our potential for goodness and morality.” This likely refers to racial and social tensions that resulted from quarantine, including tensions between individuals who do not believe in the efficacy of social distancing and tensions from the underlying racism against Asian Americans that COVID-19 exposed. The author suggests that coming together to defeat the virus through social distance will result in a society with a stronger moral backbone, which is further underscored when he asserts that “there is a better future, and we can secure it... let us take up the task, and let us be worthy of our best destiny.” In conclusion, although COVID-19 had uprooted virtually all Americans’ from their daily routines and exposed an ugly side of society, the author believes that it is an opportunity for growth.

Environmental Pollution exemplifies the disregard of the natural world Ringgold, 2017

There are Places You Don’t Walk at Night, Alone by Gil Cuadros, 1994 Manzanita, Hoover, Del Mar, The Detour’s After Hours. I told him you had to walk With an attitude. Leather isn’t thick enough for a Buck Knife Or a Corona Bottle, its end Jagged, twisted into A washboard stomach. Marc’s t-shirt turned red, The paramedics wouldn’t touch him. I filled in the holes, My fingers adding pressure On a hunter-green bandanna It changed to black, Warm in my hands. His eyes were open, His face rolled in my lap

Members of ACT UP stage a protest at the NIH. ACT UP, 1990

THERE ARE PLACES YOU DON’T WALK AT NIGHT, ALONE City of Gods is a collection of prose and poems that details the duality of HIV/AIDS epidemic as both devastating and empowering. Gil Cuadros lends visibility to an otherwise invisible group and sheds light on an existence in the age of AIDS and through a queer, chicano lens. One poem in particular detailed the stigmatization and violence that queer individuals faced in Los Angeles. “There are places you don’t walk at night” features three poems that detail the authors’ personal account of the violence they experienced in these locations. The excerpt claims “Marc’s t-shirt turned that “leather isn’t thick enough for a Buck knife or a Corona bottle,” red, The paramedics and continues to connect this vivid wouldn’t touch him. imagery of violence with Marc, - Gil Cuadros, There Are Places who, despite his t-shirt turning You Don’t Walk at Night, Alone red with blood, paramedics still refused to touch. Not only does this highlight the violence that openly queer individuals faced in a dangerous environment, it also reveals the stigmatization behind HIV/ AIDS as the paramedics refusing to touch the blood-soaken body could be interpreted as irrational fears of HIV/AIDS transmission. The author continues to describe harrowing details of filling up Marc’s as his clothes “changed to black,” and Marc eventually passing with “his eyes [were] open.” These vivid imagery serve to emphasize the death that followed Marc and many like him, not strictly because of HIV/AIDS but also because of the overt hate crimes against queer individuals, especially in underfunded neighborhoods of Los Angeles. In fact, at the end of the 1990s, this very poem served as a public service announcement on hate crimes for cable television (Gil Cuadros; Poet,Essayist Tackled AIDS Subject, 1996). Although these stigmatizations are not tied down with HIV/AIDS, they are connected because social perspectives of the disease linked it to queerness. As the poem describes, on top of the disease came not-sosubtle hate crimes that included the casual use of “faggot,” cat-calling, and physical and sexual harrassment. It is critical to understand the demeaning social attitudes towards HIV/AIDS to fully understand the scope that the virus had on both social and biological systems. IN/VISIBLE

Great Turmoil by Eli Clare, 2017 In the 1950s we used pigs at the Nevada Test Site to study the impact of radiation on humans, their skin resembling our own. Remember the extinct Passenger pigeon, Carolina parakeet, Ivory-billed woodpecker. They became Meat, plumes, collector items. I feel. Since the 1940s we’ve turned the eyes of rabbits into open sores as we develop cosmetics. Remember the air full Of toxins, the water turned To sludge, the wildfires And floods.

I feel great turmoil. Today we research the mucus that lines the lungs of elephant seals as a potential treatment, even cure, for cystic fibrosis. Remember the rivers That no longer run To the ocean, the great expanses Of forest now barren. I feel great turmoil about being human. We treat so many body-minds as if they matter only in service to our own. Remember the dams we’ve built, The prairies we’ve plowed under, The oil wells we’ve drilled. Any reckoning with personhood has to account for this destruction too.

Pigs used as test subjects for researching the effects of radiation human skin. Plumbbob Franklin, 1957

“We treat so many bodyminds as if they matter only in service to our own.” - Eli Clare, Great Turmoil GREAT TURMOIL Eli Clare’s Brilliant Imperfection: Grappling with Cure (published in 2017) includes a poetic excerpt that exposes society’s role in the degradation of the natural world. Immediately, he creates a connection between humans and pigs, imparting the connotations of filth and greed into humans. The first block of texts forces readers to reminisce about now-extinct animals, followed by the second block, which describes the increasingly unstable natural world. Then, the author describes the extinction of the natural world in the third block, and finally ends it with further destruction of nature in the final block. These images of destruction are juxtaposed by a reflection of how these destructive forces have benefited humanity, like in the case of “the eyes of rabbits” in cosmetics and the “mucus that lines the lungs of elephant seals” in the treatment for cystic fibrosis. These examples perfectly encapsulate the apathetic mindset around endocrine disruptors. Clare emphasizes the societal mindset that the threat of endocrine disrupting chemicals is merely a passing thought, especially when looking at the bigger picture of human progress. Societal outlook, therefore, seems to be blinded by the shortterm promise of progress while underestimating the long-lasting effects of EDCs. Clare ends the poem with “any reckoning with personhood has to account for this destruction too,” a powerful statement that suggests a human-role in taking accountability for a system that they greatly benefit from. The lack of understanding of the dangers of EDCs coupled with the prioritization of human progress allowed for EDCs to be pumped unrestrictedly into our environments and bodies. While activists recognize the potential harms of these chemicals, modernization accounts for the ubiquity of EDCs. Understanding how the unregulated use of chemicals for human progress and the attitudes that supported this blatant abuse of natural resources is essential in contextualizing the ubiquity of EDCs.

SOURCES: Clare, E. (2017). Brilliant imperfection: Grappling with cure. Durham, NC: Duke University Press. Coronavirus Poems to the Editor: ‘Death Too Wears a Mask’. (2020, May 22). Retrieved December 01, 2020, from https://www.nytimes.com/2020/05/22/opinion/letters/coronavirus-po ems.html Cuadros, G. (1994). City of god. San Francisco, CA: City Lights. Gil Cuadros; Poet, Essayist Tackled AIDS Subject. (1996, September 10). Retrieved December 01, 2020, from https://www.latimes.com/archives/la-xpm-1996-09-10-mn-42302-story.html Karalis Noel, T. (2020). Conflating culture with COVID-19: Xenophobic repercussions of a global pandemic. Social Sciences & Humanities Open, 2(1), 100044. https://doi.org/10.1016/j. ssaho.2020.100044 Valdiserri, R. O. (2002). HIV/AIDS Stigma: An Impediment to Public Health. American Journal of Public Health, 92(3), 341–342. https://doi.org/10.2105/AJPH.92.3.341

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COVID-19 patient being treated at Emerson Hospital in Concord, Massachusetts. Tommi Gill-Sammet, 2020/Illustration by Sarah Sullivan

IN/VISIBLE

in/visible illnesses: history

dealing with unprecedence by edward suarez

Flores, Mid 1980s Trailmix.Net/flickr

water bottles transition into using “BPA-free” materials.

Manufacturers of products like baby bottles and reusable

Mid 1980s ACT UP demonstration calling for a greater HIV response from the Reagan administration.

The United States government response to unprecedented crises have historically featured a degree of disconnect between policy and expertise, directly exacerbating health outcomes especially for underserved communities. These inadequate responses have previously been excused by a “lack of precedent,” a term that rids the government from the burden and repercussions of the resulting decimation of lives, economy, and society at large. The initial response to both the COVID-19 pandemic and HIV/AIDS epidemic reflected on this notion and illustrated how the blatant disregard of scientific institutions have contributed to widespread disaster; endocrine disrupting chemicals (EDCs) seem to follow the same path as the interplay of stakeholders in industry, healthcare, and government amounts to little intervention in the developing crisis.

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Donald Trump’s administration seemed to have waged a war on expertise, which reflected on his policies that fell short of containing the coronavirus during a critical time period where the virus was containable. Trump’s administration cycled through denial, misplaced optimism, and eventual complacency rather than implementing aggressive public health measures to minimize the virus. Rather than considering the World Health’s Organization’s (WHO) recommendations of mass testing, social distancing, and contact tracing early on, the United States seemed to adopt measures that merely suppressed deaths rather than minimized COVID-19 positive cases (COVID-19: Learning from Experience, 2020). In 2018, Donald Trump disbanded the Pandemic Response Team established by Obama despite opposition from bureaucratic experts that warned Trump of a flu pandemic as a likely threat. When COVID-19 finally reached the United States, Trump optimistically downplayed the virus and continued to do so despite warnings from world leaders, the Central Intelligence Agency (CIA), and the Health and Human Services (HHS). Finally, on March 15, Trump took the first significant step to minimizing the spread of the virus by recommending virtual learning for all students, despite the thousands of cases that have spread, largely undetected due to inadequate testing and contacting tracing, throughout the United States (Rutledge, 2020). However, the initial response was a patchwork of incoherent policies that strayed from scientific knowledge, which allowed the virus to grow past containment and disrupted the lives of the entirety of the United States. Likewise, HIV/AIDS epidemic’s poor initial response can be attributed to the miscommunication between government and scientific institutions. As in the case of COVID-19, HIV/AIDS response was most dreadful when the epidemic was most vulnerable to intervention. Again, claims of an “unprecedented” situation was undermined by the many outbreaks that CDC had effectively contained in the past; the science community generally understood how to contain viruses – it was simply a matter of translating science into policy. The director of the CDC at that time, Dr James Mason, was a public health physician by profession but answered to powerful government figures in Washington who generally had little understanding of the government’s role in disease control (Francis, 2012). This highlights an overarching idea of science being networked into politics and because of this, the faithful translation of science into the political realm is often misconstrued by politicians with different interests and backgrounds. Reagan and his administration seemed to not understand the severity of the growing HIV/AIDS epidemic. Reagan’s administration initially refused to implement HIVpreventative programs; when researchers from the CDC attempted to establish an AIDS Prevention Plan for the Nation, it was met

Passengers wearing masks during the COVID-19 pandemic in Beijing, China. Getty Images, 2020

“The United States government response to unprecedented crises have historically featured a degree of disconnect between policy and expertise, directly exacerbating health outcomes especially for underserved communities.” with rejection (Francis, 2012). Although HIV/AIDS prevention and treatment are prevalent today, the governmental early response to the epidemic was severely mishandled and accounted for an abundance of preventable suffering and death. Endocrine Disruptors have become ubiquitous with modern life, but the regulation thereof is minimal relative to its known capacity to cause environmental and physiological harm. As in the case of COVID-19 and HIV/AIDS response, endocrine disruptors are networked into politics; the added influence of corporations and capitalism serve only to complicate an already complex issue. Safety thresholds are often established by industries that have stakeholders within the industry itself, which casts doubt on the meaning of ‘safety’ through a public health lens. This disconnect between science and politics is even more evident when considering the history behind defining bisphenol-A (BPA) as deemed safe until later scientific findings deemed it as an endocrine disrupting chemical; safety, then, seems to be dependent not on the intrinsic nature of the chemical, but the political and industrial context within which the chemical exists (Vogel, 2013). The case of endocrine disruptors differs from that of COVID-19 and HIV/AIDS because the latter is very clearly a public health

risk while the former is a public health risk tied to many powerful industries. Thus, the lack of harmony between science and policy is even more exaggerated with EDCs. The first legally binding governmental response to EDCs came in the late 1990s. The EDSP of the EPA employed a two-tiered program to assess substance interaction with the endocrine system and the development of a concentration-response curve in animal models (Vogel, 2013). While this represents a major milestone in addressing the issue, it also comes decades after endocrine disrupting chemicals have already infiltrated the majority of the natural world. Furthermore, a lack of early international response prevents endocrine disruptors from being addressed as comprehensively as it should. The initial response to COVID-19, HIV/AIDS, and Endocrine Disruptors all featured a lack of connection between scientific expertise and governmental policies that amounted to unnecessary suffering and death in the case of COVID-19 and HIV/AIDS. The extent of damage that EDCs have and will continue to cause is still unknown, which begs the question: is it too late to intervene? Will the now-subtle effects of EDCs transform into disaster with the coming years? And at the root of it all, should the United States pursue more aggressive regulations of EDCs?

SOURCES: Francis, D. P. (2012). Deadly AIDS policy failure by the highest levels of the US government: A personal look back 30 years later for lessons to respond better to future epidemics. Journal of Public Health Policy, 33(3), 290–300. https://doi.org/10.1057/jphp.2012.14 Hecker, M., & Hollert, H. (2011). Endocrine disruptor screening: Regulatory perspectives and needs. 14. Rutledge, P. E. (n.d.). Trump, COVID-19, and the War on Expertise. American Review of Public Administration, 7. The Lancet. (2020). COVID-19: Learning from experience. The Lancet, 395(10229), 1011. https://doi.org/10.1016/S0140-6736(20)30686-3 Vogel, S. A. (2013). Is it safe? BPA and the struggle to define the safety of chemicals. Berkeley, CA: University of California Press.

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in/visible illnesses: biology

THE ENDOCRINE SYST E M A N D D I S RU P TO RS By Drake Hipe

WHAT IS THE ENDOCRINE SYSTEM? Many living organisms, including all mammals, fish, and birds, possess an endocrine system. Also known as the hormone system, the endocrine system is responsible for all biological processes in humans such as human development and bodily functions (EPA, 2017). The endocrine system is made up of three major parts: glands, hormones, and receptors. Major glands that help produce hormones include the hypothalamus, pituitary gland, thyroid gland, adrenal glands, pancreas, and gonads. In addition, the endocrine system relies on chemical messengers known as hormones, which are essential in regulating biological processes. Some well known examples of hormones include insulin, estrogen, and testosterone. Receptors can be found in organs and tissues and they are responsible for recognizing and responding to the hormones released by the endocrine system (EPA, 2017). One note is that cells and organs that are capable or releasing and responding to hormones can also serve as expanded endocrine functions. This ensures that even paracrine, autocrine, and juxtacrine functions are considered as well as the removal of the blood circulation for hormones as a prerequisite (Chrousos, 2007).

MECHANISMS OF EDCS An Endocrine Disrupting Chemical or Compound (EDC) is a natural or synthetic compound that disrupts

or affects homeostasis through the hormonal system. In 2002, the World Health Organization (WHO) had defined EDCs: “An endocrine disruptor is an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub)populations” (Combarnous, 2017). The introduction to the human body may come in a variety of forms such as “environmental or inappropriate developmental exposures”, which holds the potential to alter organism function and response. EDCs can affect one or multiple parts of the endocrine system and knowledge of their effects has grown over the years. Biologically, EDCs can affect not only various receptors but also “An endocrine enzymatic processes such as metabolism and disruptor is an biosynthesis. Endocrine exogenous substance disrupting chemicals or mixture that alters primarily interfere with function(s) of the the endocrine system via two mechanisms: endocrine system and The first is to directly consequently causes interfere with the adverse health effects receptors of certain in an intact organism, hormones ultimately or its progeny, or (sub) affecting downstream chemical processes. populations.” The second is to alter concentrations of endogenous (originating from the body) active hormones through “stimulation or inhibition of either their synthesis, or degradation, or availability.” The issue is that hormone-receptor pairs are specialized, yet the introduction of thousands of molecules—ultimately becoming EDCs if they eventually

EDCs, COVID-19, & HIV/AIDS Endocrine

disrupting

chemicals

are

ubiquitous

the

environment and in our consumption. They can be found in our food, our water, and our air. Thousands of products contain EDCs including skin products, hair products, clothing, furniture, and even in electronics. Even if an individual were to be conscious of EDCs within products, it is nearly impossible to avoid. They reside within each and every one of us, yet we do not fully understand the extent of their influence on our bodies—there is much to be desired regarding its effects on viruses such as COVID-19 and EDCs are found everywhere in the environment, including plastics and the water we drink. Getty Images

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HIV. There are many EDCs found within our bodies so it makes it quite hard to study the effects of specific EDCs. However...

affect the hormonal system—that have not been selected against during human evolution are able to “more or less, accommodate the receptors binding site and promote receptor activation or inactivation” (Combarnous, 2017). Many EDCs can be found as ingredients to synthetic products, byproducts of industrial processes, or even natural chemicals found in human and animal food. Exposure to EDCs is correlated to environmental conditions and their presence in human lives remains persistent and widespread (Diamanti-Kandarakis et al., 2009). Due to the lack of extensive, long-term studies as well as the difficulty in studying EDCs mixture exposure within humans, there is still much work to be done in order to fully understand the extent that endocrine disruptors exert their influence within humans.

WHY DO THEY MATTER? EDCs exert actions which can affect our bodies in many ways. Their ability to alter the hormonal balance of the body is associated with adverse reproductive and developmental issues in humans. Still, they are found everywhere from the food humans eat to the environments that surround and sustain humans, consequently leading to higher and prolonged EDC exposure. Important issues in endocrine disruption include exposure age (human stage of development), exposure latency, effects of mixture EDC exposure, nontraditional dose-response dynamics such as long-term, low dose exposure, and transgenerational, epigenetic effects (Diamanti-Kandarakis et al., 2009). There is still much work to be done in thoroughly understanding the extent that EDCs exert their effects especially as the environment, people, and patterns of EDC production are constantly changing. However, a better understanding of the complexities of EDC interactions as well as the relationship between EDCs and health outcomes can help inform and shape better policies and approaches to preventing and treating health, diseases, and illnesses.

The Hormonal System from The Endocrine Society

continued from page 13... we do understand that the endocrine system, or hormonal system, is vital to regulating the body and its functions—including the immune system. Further long-term research exploring EDC’s effects on susceptibility to pathogenic agents can shed light on possible interventions directed at hormone regulation or endocrine disrupting mechanisms to mitigate or prevent detrimental health effects caused by viruses. Exploring the intersectionality between endocrine disruption and viruses, as well as the parallels between HIV and COVID, opens avenues of healthcare directed at biological and medical solutions while maintaining awareness of social implications. The next few pages explores and draws connections between the mechanisms of endocrine disrupting

SOURCES: Chrousos G. P. (2007). Organization and Integration of the Endocrine System. Sleep medicine clinics, 2(2), 125–145. https://doi.org/10.1016/j. jsmc.2007.04.004

chemicals to HIV and COVID-19. There are multiple links that can be drawn such as the intersectionality of diabetes as an adverse health effect. Yet, there is understandably still so much to learn and explore about EDCs and

Combarnous, Yves (2017). Endocrine Disruptor Compounds (EDCs) and agri culture: The case of pesticides. Comptes Rendus Biologies, 406-409. https//doi.org/10.1016/j.crvi.2017.07.009

pathogens. The contents of this magazine are curated

Diamanti-Kandarakis, E., Bourguignon, J. P., Giudice, L. C., Hauser, R., Prins, G. S., Soto, A. M., Zoeller, R. T., & Gore, A. C. (2009). Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocrine re views, 30(4), 293–342. https://doi.org/10.1210/er.2009-000

EDCs, COVID, and HIV, but to open new perspectives and

Environmental Protection Agency (EPA). (2017). What is the Endocrine System? Endocrine Disruption. https://www.epa.gov/endocrine-disrup tion/what-endocrine-system

importance of continuing to study EDCs, which do not

not to confidently answer the intersectionality between avenues of care in handling endocrine disruptors and its connections to illnesses as well to remind people the pose immediate health risks.

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in/visible illnesses: biology

AN INTRODUCTION TO VIRUSES MIKE MATTHEWS Perhaps the first thing that needs to be explained in order to understand the biology of both HIV/AIDs and COVID-19 is what a virus is and how it works. A virus is a microscopic infectious agent composed of genetic material (DNA or RNA) enclosed in a protein coat. A virus is unable to reproduce by itself and instead must reproduce by injecting its genetic material into a host cell. From there a virus may employ one of two different strategies. In a lytic cycle, the viral DNA uses the host cell’s machinery to replicate and form proteins. The replicated viruses then cause the cell to lyse and the viruses are set free to infect other cells. In a lysogenic cycle, the injected viral DNA becomes incorporated into the host cell’s genome and each time the cell replicates its DNA, the viral DNA is also replicated and passed on to daughter cells. In this case, the virus may remain dormant for a period of time within its host’s genome before causing cell lysis and/or disease (National Geographic, 2019). Viruses cause disease by killing cells and/or disrupting normal cell function. Furthermore, many of the HIV STRUCTURE Dominguez, 2019 symptoms typically associated with viruses, such as fever, headache, and fatigue are due to our body’s immune systems working to fight off the infection (Drexler, 2010). SOURCES: Dominguez, M. (2019, July 23). HIV Structure [Digital image]. Retrieved fromhttps://step1.medbullets.com/ immunology/105067/human-immunodeficiency-virus-acquired-immunodeficiency-syndrome Drexler, M., & Medicine (US), I. of. (2010). How Infection Works. In What You Need to Know About Infectious Disease. National Academies Press (US). https://www.ncbi.nlm.nih.gov/books/ NBK209710/ National Geographic Society. (2019, May 14). Viruses. Retrieved November 20, 2020, from https://www.nationalgeographic. org/encyclopedia/viruses/

COVID-19 STRUCTURE The Week, 2020

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TheWeek. (2020, June 30). [Coronavirus Structure]. Retrieved from https://www.theweek.in/news/health/2020/06/30/xrays-sizeup-coronavirus-structure-at-room-temperature.html

in/visible illnesses: biology

HIV:

STAGES OF INFECTION, PROPHYLAXIS AND TREATMENT, AND ENDOCRINE EFFECTS.

BY SHEEL SHAH

PLACING HIV/AIDS IN CONVERSATION WITH EDCs AND COVID-19 At the outset of this article, I would like to establish its central aims: i) to examine the basic biology and etiology of HIV/AIDS, while at the same time ii) tying it back to the crux of this magazine by placing it in conversation with EDCs and COVID-19. This is because each of these seemingly distinct phenomena are inextricably intertwined; left untreated, HIV can quickly progress to AIDS in which opportunistic infections exploit the compromised immune and endocrine function of patients living with the virus, whereas current-day antiretroviral therapies employed in HIV’s use have been implicated in downstream immune system changes, metabolic abnormalities, and in certain cases, even hormonal dysregulation (such as altered estradiol levels in pregnant females living with HIV) (McDonald et al., 2018). Tying this back to COVID-19 paints an even more holistic picture; the risk of

disease for both HIV and COVID-19 is significantly elevated in BIPOC and other marginalized, under-resourced, and disenfranchised groups (Juthani & Forman, 2020d). These roots of disease occurrence are further exacerbated by current understandings of COVID-19’s function, which suggests that its symptomology and risk is elevated for those over the age of 75 and those with pre-existing health conditions such as diabetes, respiratory failure/physiological inadequacy, kidney failure chronic obstructive pulmonary disease (COPD) (Juthani & Forman, 2020d). This highlights a key point: those living with HIV carry the risk of endocrine disruption through antiretroviral therapy, which could conceivably elevate their risk of suffering adverse symptomology upon acquisition of COVID-19.

THE BASIC BIOLOGY OF HUMAN IMMUNODEFICIENCY VIRUS (HIV), AND THE PHASES OF DISEASE EXPRESSION HIV has gained a tremendous deal of awareness in recent decades, notably after its historic stigmatization (and the downstream consequences observed) during its rapid spread in the 1980s and 1990s. An understanding of the basic biology underlying HIV can be beneficial in understanding its effects, proposed treatments, and challenges perpetuating its spread today. HIV belongs to a group of viruses termed retroviruses, specifically lentiviruses, which are known to lead to disease expression gradually (CDC, 2020c). Since the virus is unable to replicate independently, it infects lymphocytes of the immune system known as T-lymphocytes (or ‘helper T-cells’). This is significant because T-lymphocytes (often identified by a protein marker on their coat termed CD4) are important cell “signalers” or “activators” of and within the immune system; they activate cytotoxic T-cells (CD8 cells) and B cells in the immune response, which then serve to fight pathogens impacting the body (CDC, 2020c). When an individual is first infected with HIV (most commonly through unprotected sex with an infected partner) he/she/they experiences a rapid increase in the viral load of HIV; this is accompanied by a subsequent decline in the endogenous levels of T-lymphocytes (which are forced into programmed cell death following infection with HIV). This stage of high viral load and decreasing CD4/helper T-cells is typically referred to as the first phase of HIV infection. It is during this phase when individuals are considered the most “contagious” and when those living with the virus have the highest probability of transmitting HIV to potential partners. Individuals in this stage typically experience flu-like symptoms (a phenomenon formally termed acute HIV syndrome, which some have described as the “worst flu of their lives) whereas others may experience significantly milder symptomology (Khan Academy Medicine, 2015b); that said, lymph nodes are typically swollen at this stage and perhaps a key indicator to visit a physician. In the second phase of HIV, the immune system begins “seroconversion”— or the production of antibodies against HIV. In this second phase of HIV

The three stages of HIV infection and the associated CD4 and HIV RNA at each stage. WebMD, 2020

infection (often termed the “latency phase”) the viral load begins to stabilize as does the CD4 cell count. Those living with HIV typically appear asymptomatic during this phase of the infection; and, without treatment, the virus slowly reduces the number of T-lymphocytes in the body (Khan Academy Medicine, 2015b). This phase is relatively lengthy, and, without treatment, typically lasts around ten years. Failure to take action can then lend to the final stage of HIV, which is when the body reaches a critically low level of T-lymphocytes, and, accordingly, becomes susceptible to infections by pathogens that typically would not thrive in those with a functioning immune system; the near absence of T-lymphocytes creates a virtually absent/ineffective immune system, rendering heightened susceptibility to such “opportunistic” infections, thereby culminating in the final stage of HIV infection termed acquired immunodeficiency syndrome or AIDS (CDC, 2020c; Khan Academy Medicine, 2015b). IN/VISIBLE 16

WHY IS HIV SO EVASIVE?

The crown-like spikes of a coronavirus. Henderson et al., 2020

HIV poses a particularly difficult public health challenge because it evades the typical checkpoints of the human immune system. First, the original, RNA genetic component of HIV integrates itself into the DNA of human immune system cells; these cells (termed “latently-infected” cells) often surpass recognition by the immune system, and persist until cell death. Notably, these cells may also remain dormant for extended durations of time—that is until they are stimulated to replicate (the nature of such stimulation still remaining relatively ambiguous) (Kuo & Lichterfeld, 2018). Since a portion of these cells are long-lasting memory T-cells, a “reservoir” of latently-infected cells becomes established—and often bypasses suppression with antiretroviral medications (Kuo & Lichterfeld, 2018).

MINIMIZING THE SPREAD AND IMPACT OF HIV: PROPHYLAXIS AND TREATMENT Prophylaxis measures are defined as those used to stop or prevent disease; these typically hold significant public health potential in continuing to minimize the rates of disease transmission. In the context of HIV, two measures of prophylaxis are worth mentioning—pre-exposure prophylaxis (or PrEP) and post-exposure prophylaxis (or PEP). PrEP refers to the daily use of antiretroviral medication to prevent the acquisition of HIV; it is used solely by those who are negative for HIV, and fear potential exposure to the virus either through sexual activity or intravenous drug use (CDC, 2020b). It is worth mentioning here that while the LGBTQIAA+ is certainly at a disproportionately higher risk for HIV infection, as are ethnic and gender minorities, the virus is not confined to these populations; as such, PrEP is a plausible preventative modality for all those who are at risk of HIV infection. The FDA has approved two medications for pre-exposure prophylaxis: Truvada (emtricitabine in combination with tenofovir disoproxil fumarate) and Descovy (emtricitabine in combination with tenofovir alafenamide) (CDC, 2020b). The CDC currently boasts an approximately 99% effectiveness rate for those using approved PrEP medication (CDC, 2020b). On the contrary, PEP is a treatment modality for those who believe they have been exposed to HIV; it is prescribed within 72 hours of viral exposure and combines three anti-retroviral medications in a 28-day treatment in an effort to limit the latently-

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infected HIV cells and HIV viral reservoir within the body (CDC, 2020a). Assuming such preventative modalities are not employed early enough to prevent infection, the first-line treatment modality for those with HIV is anti-retroviral therapy (ART)—which typically makes use of several anti-retroviral medications used in combination. Treatment with more than one anti-retroviral drug is a hallmark feature of ART—it diminishes the likelihood of HIV becoming resistant to any one particular drug, thereby decreasing the likelihood of acquiring immune deficiency (Khan Academy Medicine, 2015a). ART is effective because it inhibits the fusion (through fusion inhibitors), reverse transcription (through nucleoside reverse transcriptase inhibitors [NRTIs] and nonnucleoside reverse transcriptase inhibitors [NNRTIs]), integration (through integrase inhibitors), and protein production (through protease inhibitors) of HIV in CD4 T-cells; it attacks the typical mechanisms used by these viral pathogens to proliferate, in effect minimizing their impact within the body (Khan Academy Medicine, 2015a). An important caveat of ART, however, is that it necessitates consistency and compliance to remain effective, and is by no means a cure—it is unable to destroy latently-

National Library of Medicine, 2020

infected cells that have already formed the HIV reservoir in early stages of the infection (Khan Academy Medicine, 2015a). ART is particularly significant in the context of this article because while it certainly plays a key role in minimizing the health consequences associated with HIV, it is known for its endocrine-disrupting effects—a topic which we will cover next.

A CLOSER LOOK: ENDOCRINE DISRUPTING CHEMICALS OF HIV AND ART At the outset of this article, HIV was placed in conversation with EDCs and COVID-19; specifically, how its etiology and potential treatment could lead to downstream endocrine disruption, thereby elevating the risk of severe illness upon acquisition of COVID-19. This section will more thoroughly examine the specific endocrine disrupting effects of HIV and treatment modalities that prove effective in its management. At its onset, the vast majority of endocrine disrupting properties associated with HIV were the result of opportunistic infections acquired in phase 3 of the infection, resulting in downstream changes to pituitary, adrenal, metabolic, and gonadal function (Zaid & Greenman, 2019). In the era of antiretroviral therapy, however, there are a new set of challenges; as a peer reviewed chapter in Endocrine Manifestations of HIV infections makes clear both “protease inhibitors and NNRTIs are associated with multiple abnormalities in glucose and lipid metabolism, such as insulin resistance, increased triglycerides, and increased levels of low-density lipoprotein cholesterol” (Girei & Fatima, 2013). Indinavir—a type of antiretroviral medication (ARM)—has also been implicated in causing the most insulin resistance, whereas another ARM, ritonavir, is thought to cause the most hypertriglyceridemia (Girei & Fatima, 2013).

SOURCES:

Mechanisms of Endocrine dysfunction in patients with HIV.

Common Endocrine abnormalities in HIV infected patients. (Girei & Fatima, 2013)

Centers for Disease Control and Prevention. (2020a, May 13). Learn About PEP | Preventing New HIV Infections | Clinicians | HIV | CDC. Post-Exposure Prophylaxis (PEP). https://www. cdc.gov/hiv/clinicians/prevention/pep.html Centers for Disease Control and Prevention. (2020b, May 19). Learn About PrEP | Preventing New HIV Infections | Clinicians | HIV | CDC. Pre-Exposure Prophylaxis (PrEP). https:// www.cdc.gov/hiv/clinicians/prevention/prep.html Centers for Disease Control and Prevention. (2020c, November 3). About HIV/AIDS | HIV Basics | HIV/AIDS | CDC. About HIV. https://www.cdc.gov/hiv/basics/ whatishiv.html Girei, B. A., & Fatima, S.-B. (2013). Endocrine Manifestations of HIV Infection. Current Perspectives in HIV Infection. https://doi.org/10.5772/52684 Henderson, L. J., Reoma, L. B., Kovacs, J. A., & Nath, A. (2020). Advances toward Curing HIV-1 Infection in Tissue Reservoirs. Journal of Virology, 94(3). https://doi.org/10.1128/JVI.0037519 Juthani, P. V., & Forman, H. (2020, December 1). Five lessons from the AIDS epidemic on how to cope with COVID-19. USA TODAY. https://www.usatoday.com/story/opinion/2020/12/01/ covid-lessons-from-hiv-epidemic-world-aids-day-column/6458569002/ Khan Academy Medicine. (2015, June 26). Treating HIV: Antiretroviral drugs | Infectious diseases | NCLEX-RN | Khan Academy. https://www.youtube.com/watch?v=GR9d9wrOl5E&ab_ channel=khanacademymedicine Khan Academy Medicine. (2015b, June 26). What is HIV and AIDS | Infectious diseases | NECLEX-RN | Khan Academy. https://www.youtube.com/watch?v=17pfZUlAqow&ab_ channel=khanacademymedicine Kuo, H.-H., & Lichterfeld, M. (2018). Recent progress in understanding HIV reservoirs. Current Opinion in HIV and AIDS, 13(2), 137–142. https://doi.org/10.1097/ COH.0000000000000441 Kuo, H.-H., & Lichterfeld, M. (2018). Recent progress in understanding HIV reservoirs. Current Opinion in HIV and AIDS, 13(2), 137–142. https://doi.org/10.1097/ COH.0000000000000441 Manoto, S. L., Lugongolo, M., Govender, U., & Mthunzi-Kufa, P. (2018). Point of Care Diagnostics for HIV in Resource Limited Settings: An Overview. Medicina, 54(1), 3. https://doi. org/10.3390/medicina54010003 McDonald, C. R., Conroy, A. L., Gamble, J. L., Papp, E., Hawkes, M., Olwoch, P., Natureeba, P., Kamya, M., Silverman, M., Cohan, D., Koss, C. A., Dorsey, G., Kain, K. C., & Serghides, L. (2018). Estradiol Levels Are Altered in Human Immunodeficiency Virus-Infected Pregnant Women Randomized to Efavirenz-Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 66(3), 428–436. https://doi.org/10.1093/cid/cix772 National Library of Medicine. (2020). HIV Prevention | Continue the Conversation! https://news.nnlm.gov/nacc/hiv-prevention-prep-vs-pep/ Zaid, D., & Greenman, Y. (2019). Human Immunodeficiency Virus Infection and the Endocrine System. Endocrinology and Metabolism, 34(2), 95–105. https://doi.org/10.3803/ EnM.2019.34.2.95

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in/visible illnesses: biology MUCH? COVID-19 is known to affect individuals in significantly different ways, causing mild symptoms in some while resulting in death in others. According to the World Health Organization, adults 60 and older, individuals with lung or heart disease, individuals with diabetes, and individuals with conditions that affect their immune system are considered high risk when it comes to COVID-19 (WHO, 2020). There are a number of biological explanations for such differential COVID-19 risks and outcomes among individuals.

BIOLOGY OF COVID-19 Why some are affected more than others and why EDCs matter. By Mike Matthews

WHAT IS COVID-19 HOW IS IT SPREAD?

AND

Coronaviruses are a specific family of viruses known for having crown-like spikes on their protein surface which they use to help them gain entry into cells. SARS-CoV-2, better known as COVID-19, is a coronavirus that uses its spikes to enter epithelial cells by way of a receptor known as Angiotensin Converting Enzyme II (ACE2). ACE2 plays a critical role in homeostasis throughout the body and is particularly important for maintaining fluid-salt balance and blood pressure. ACE2 is also critical for cardiac function and for beta cell function which is necessary for the production and secretion of insulin (Clutter, 2020). In the body, ACE2 is expressed in epithelial cells of the lungs, small intestine, arteries and veins, and in arterial smooth muscle cells (Hamming et al., 2004). Provided that COVID-19 gains entry

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The crown-like spikes of a coronavirus. WebMD, 2020

into cells via ACE2, cells and tissues that express ACE2 are susceptible to infection and destruction by COVID-19. Given that ACE2 is expressed in the lungs, the lungs are an optimal site for COVID-19 infection through inhaled respiratory particles (Clutter, 2020). That being said, COVID-19 is primarily spread via respiratory droplets released when an infected person coughs, talks, sneezes, or breathes while in close contact with another person (CDC, 2020). COVID-19 can cause a number of symptoms which vary from person to person. These symptoms include coughing, shortness of breath, difficulty breathing, fever, muscle and body aches, vomiting, diarrhea, and loss of taste or smell among other things (CDC, 2020). As with other viruses, these symptoms result from cell and tissue damage along with the body’s own immune response. Furthermore, in some cases of COVID-19 individuals have continued to display an immune response after the virus has been controlled which results in a widespread inflammatory response known as a “cytokine storm.” This is particularly dangerous as it can cause significant damage to the lungs and other organs and ultimately lead to death (Weill Cornell Medicine, 2020). WHY DO COVID-19 OUTCOMES DIFFER SO

At the biological level, differences in COVID-19 outcomes among individuals are largely due to differences in immune system function. One reason why the elderly are particularly at risk is because immune system function declines with age leaving the body less equipped to fight off infections like COVID-19. Reduced immune system functioning is also why individuals with diabetes or individuals on immune-suppressing drugs are also particularly susceptible to severe COVID-19 infection (Live Science, 2020). In cases of lung and heart disease, individuals with these conditions are less able to withstand the biological stresses associated with COVID-19. Since COVID-19 attacks the lungs, it becomes more difficult for the body to obtain oxygen and the heart must work harder to pump oxygenated blood throughout the body. As a result, individuals with conditions that compromise lung and heart function, such as lung disease, asthma, and heart disease, are at risk for severe COVID-19 complications (Live Science, 2020).

“At the biological level, differences in COVID-19 outcomes among individuals are largely due to differences in immune system function.”

The ACE2 receptor has also been examined as a potential reason why some individuals fare worse than others when infected with COVID-19. For one thing, it has been hypothesized that men may be dying from COVID-19 at higher rates than women because the gene for ACE2 is located on the X chromosome. Provided that women have two X chromosomes while men only have one, females may have the ability to compensate for harmful ACE2 variants whereas men do not (Zimmer, 2020). Furthermore, diabetes, hypertension, cardiovascular disease and obesity are all associated with increased ACE2 expression and this may allow for more COVID-19 entry points in cells throughout the body leading to more severe infection (Wallis, 2020). EDCs AND COVID-19 Although current research is limited, evidence has suggested that exposure to EDCs may also influence COVID-19 outcomes. For example, a recent study in which scientists employed a computational systems biology approach to examine whether or not there

are proteins that are associated with both EDCs and COVID-19 outcomes found several biological pathways that are influenced by EDCs and that may also be involved in COVID-19 severity. Of these pathways, two that were found to be of particular importance were the Th17 and AGE/RAGE signaling pathways, both of which are involved in inflammation. While the researchers did not implicate specific EDCs, this work represents an important first step in the investigation of the relationship between EDCs and COVID-19 (Wu et al., 2020). Other research has focused on how exposure to EDCs can lead to severe Covid-19 outcomes by raising the risk of chronic illnesses and/or by affecting immune system function. For example, a number of studies have associated EDCs with metabolic disorders including obesity and diabetes along with other chronic illnesses such as cancer. This is significant because all of these conditions put individuals at higher risk for

complications from COVID-19 (Crawford, 2020). Moreover, research has linked a number of EDCs to reduced immune system function. These chemicals include a number of pesticides, polychlorinated biphenyls (PCBs), and polyaromatic hydrocarbons (PAHs) among others (Kostoff et al., 2020). Provided that immune system function is critical to overcoming COVID-19, exposure to these chemicals may be more harmful now than ever before.

“Research has linked a number of EDCs to reduced immune function. These chemicals include a number of pesticides, polychlorinated biphenyls (PCBs), and polyaromatic hydrocarbons (PAHs) among other things”

SOURCES: Clutter, C. (2020, June 5). The Biology and Immunology of COVID-19 Susceptibility. Retrieved November 20, 2020, from https://asm.org/Articles/2020/June/The-Biology-and-Immunology-of-COVID-19-Susceptibil

Lam, G. (2020, May 25). [Fighting Covid-19]. Retrieved from https://www.nytimes.com/2020/05/25/well/live/to-fightcovid-19-dont-neglect-immunity-and-inflammation.html

COVID-19 High risk groups. (2020, March). Retrieved November 20, 2020, from https://www.who.int/westernpacific/ emergencies/covid-19/information/high-risk-groups

Live Science Staff. (2020, June 19). Why COVID-19 kills some people and spares others. Here’s what scientists are finding. Retrieved November 20, 2020, from https://www.livescience.com/why-covid-19-coronavirus-deadly-for-somepeople.html

COVID-19: Why is it mild for some, deadly for others? (2020, April 17). Retrieved November 20, 2020, from https:// weillcornell.org/news/covid-19-why-is-it-mild-for-some-deadly-for-others Crawford, K. (2020, November 03). How Chemicals Like PFAS Can Increase Your Risk of Severe COVID-19. Retrieved November 20, 2020, from https://www.discovermagazine.com/health/how-chemicals-like-pfas-can-increase-yourrisk-of-severe-covid-19 Gaertner, J. (2020, May 14). [ACE2 binding SARS-CoV-2]. Retrieved from https://theconversation.com/what-is-theace2-receptor-how-is-it-connected-to-coronavirus-and-why-might-it-be-key-to-treating-covid-19-the-expertsexplain-136928 Hamming, I., Timens, W., Bulthuis, M. L. C., Lely, A. T., Navis, G. J., & van Goor, H. (2004). Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. The Journal of Pathology, 203(2), 631637. https://doi.org/10.1002/path.1570

Wallis, C. (2020, August 20). Why Some People Get Terribly Sick from COVID-19. Retrieved November 20, 2020, from https://www.scientificamerican.com/article/why-some-people-get-terribly-sick-from-covid-19/ WebMD.(2020, September 29). [Coronavirus structure]. Retrieved from https://www.webmd.com/lung/coronavirus What you should know about COVID-19 to protect yourself and others. (2020, June 6). Retrieved November 19, 2020, from https://www.cdc.gov/coronavirus/2019-ncov/downloads/2019-ncov-factsheet.pdf Wu, Q., Coumoul, X., Grandjean, P., Barouki, R., & Audouze, K. (2020). Endocrine disrupting chemicals and COVID-19 relationships: A computational systems biology approach. MedRxiv. https://doi.org/10.1101/2020.07.10.20150714 Zimmer, K. (2020, February 24). Why Some COVID-19 Cases Are Worse than Others. Retrieved November 20, 2020, from https://www.the-scientist.com/news-opinion/why-some-covid-19-cases-are-worse-than-others-67160

Kostoff, R. N., Briggs, M. B., Porter, A. L., Hernández, A. F., Abdollahi, M., Aschner, M., & Tsatsakis, A. (2020). The underreported role of toxic substance exposures in the COVID-19 pandemic. Food and Chemical Toxicology, 145, 111687. https://doi.org/10.1016/j.fct.2020.111687

COVID-19 binding to ACE2 receptor. Gaertner, 2020

Lam, 2020

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in/visible illnesses: biology

DIABETES MELLITUS

A BIOLOGICAL LINK BETWEEN EDCs, HIV/AIDS, AND COVID-19

Adobe Stock, 2020

BY MIKE MATTHEWS

WHAT IS DIABETES? Diabetes mellitus is a chronic health condition that occurs when the body cannot properly process glucose due to an inability to effectively produce or use insulin, the hormone that allows cells to take in glucose from the bloodstream for energy. Untreated, diabetes leads to abnormally high blood sugar which can cause a number of long-term health problems including cardiovascular disease, nerve damage, kidney damage, eye damage, foot damage, skin conditions, Alzheimerâ&#x20AC;&#x2122;s disease, and Depression (Mayo Clinic, 2020).

factors play a role in the development of type 2 diabetes, a number of other factors have also been implicated including physical inactivity and being overweight and/or obese. Type 2 diabetes is most often diagnosed in adults although today more children are being diagnosed with the condition likely due to the increasing rate of childhood obesity in the US (Mayo Clinic, 2020).

As of 2018, more than 34.2 million, or approximately 1 in 10 Americans were living with diabetes and an additional 88 million American There are two main types of diabetes: type 1 and type 2. In type 1 adults were prediabetic. Moreover, diabetes was most prevalent diabetes, the pancreas does not produce enough insulin or produces no among racial and ethnic minorities with American Indians/Alaska insulin at all. Type 1 diabetes is thought to be caused by an autoimmune Natives, Hispanics, and non-Hispanic blacks having the highest reaction in which the body percentage of existing cases destroys the insulin producing (National Diabetes Statistics beta-cells in the pancreas. Genetic Report, 2020). For the purposes of factors can predispose individuals our project, diabetes is significant to developing type 1 diabetes because it represents an important and although type 1 diabetes biological connection between can occur at any age, it is most EDCs, HIV/AIDs, and COVID-19 often diagnosed in children and as it demonstrates how all three young adults. Type 1 diabetes is conditions are related via their less common than type 2 and it effects on both metabolism and accounts for approximately 5-10% immune system function. More of cases (CDC, 2020). specifically, exposure to EDCs can influence the development Type 2 diabetes is caused by the of diabetes, people living with body developing a resistance HIV/AIDs are more likely to to insulin. In response to this have type 2 diabetes than resistance, the pancreas overthe general population, and produces insulin which over time individuals with diabetes are can damage beta-cells to the point at risk of developing severe Age-adjusted prevalence of diagnosed diabetes by race and sex among that they may no longer be able adults aged 18 years or older, US, 2017-2018. complications from COVID-19. CDC, 2020 to produce insulin. While genetic

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EDCs AND DIABETES Regarding the connection between EDCs and Diabetes, a growing body of research suggests that exposure to EDCs can promote the development of diabetes. For example, a number of cross-sectional studies have shown that high levels of persistent organic pollutants

(POPs) in humans is associated with diabetes. Furthermore, a meta-analysis of all of the cross-sectional and prospective studies on the relationship between EDC exposure and diabetes prevalence published in 2016 found significant relationships between levels of dioxins, polychlorinated biphenyls (PCBs), organochloride pesticides, bisphenol A (BPA) and diabetes prevalence. Finally, a meta-analysis of seven mother-child cohorts published in 2017 found a positive relationship between prenatal exposure to Dichlorodiphenyltrichloroethane (DDT) and subsequent weight gain in children (Lind and Lind, 2018). This is relevant because as previously mentioned, being overweight is a risk factor for the development of type 2 diabetes.

Insulin secretion in pancreatic beta-cells. Almekinder, 2016

HIV/AIDS AND DIABETES

The connection between EDC exposure and diabetes is also supported by a number of experimental studies. For example, several experimental studies in rodents have shown that developmental exposure to EDCs can affect the development of the pancreas and its insulin producing beta-cells leading to impaired

HIV/AIDs relates to diabetes because individuals living with HIV/ AIDs are more likely to develop diabetes than uninfected individuals. While statistical estimates vary, one study, which used nationally representative survey data (2009-2010) from the Medical Monitoring Project and the National Health and Nutrition Examination Survey found that diabetes prevalence was 3.8% higher in adults living with HIV/ AIDs compared with adults from the general population (HernandezRomieu et al., 2017). Furthermore, a different study which used data from the 2005 Multicenter AIDs Cohort Study of gay and bisexual men with and without HIV found that men with HIV were four times more likely to have diabetes than men without HIV, and that this statistic remained even after controlling for other diabetes risk factors such as age and body mass index (Sarkar and Brown, 2019).

glucose metabolism in adult rats. Moreover, experiments on zebrafish embryos showed that developmental exposure to a number of EDCs including PCBs, phthalates, arsenic, and perfluorooctanesulfonic acid (PFOS) affected the development of the pancreas and pancreatic beta-cells. Provided that pancreatic beta-cells produce insulin, which is required for proper glucose metabolism it’s easy to see how improper pancreatic development due to EDC exposure could lead to the development of diabetes in humans. Given the relationship between EDC exposure and diabetes, it’s possible that EDCs could be partially responsible for the unequal distribution of diabetes in the US. As previously mentioned, diabetes in the United States is most common among Native American, Non-Hispanic Black, and Hispanic American adults (Spanakis and Golden, 2014). Furthermore, it is well documented that EDC exposure is pattered along racial lines and studies have shown that exposure to chemicals like phthalates, BPA, parabens, and polybrominated diphenyl ethers is greater in non-white Americans (James-Todd et al., 2016). That being said, it’s very possible that EDCs may play a role in the unequal distribution of diabetes in the United States.

C and hepatitis C is known to raise the risk of diabetes development. Furthermore, the chronic inflammation that is associated with HIV can also raise one’s risk of diabetes (Sarkar and Brown, 2019). While it may be a stretch to imply that HIV/AIDs has significantly impacted the prevalence and distribution of diabetes in the United States, the risk of diabetes is nevertheless a significant aspect of the HIV/ AIDs experience and it is one way in which HIV/AIDs is connected to EDCs and COVID-19.

There are a number of reasons why individuals living with HIV/ AIDs are more prone to diabetes. One major risk factor for diabetes development in people living with HIV/AIDs is treatment with older generation antiretroviral therapies (ART) including protease inhibitors (PI), nucleoside reverse transcriptase inhibitors, and integrase strand transfer inhibitors (Sarkar and Brown, 2019). This association between older generation ARTs and diabetes is supported by a number of different epidemiological studies and while treatment with newer generation ARTs is less likely to be associated with diabetes, newer generation ARTs are still associated with lipodystrophy, or abnormal fat distribution, and weight gain, both of which increase the risk of diabetes (Sarkar and Brown, 2019). In addition to ARTs, there are a number of other HIV/AIDs associated risk factors for diabetes. For one thing, approximately 25% of people living with HIV/AIDs in the United States are co-infected with hepatitis

Risk factors for insulin resistance and type 2 diabetes. Duncan, 2020

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Davis, 2020

COVID-19 AND DIABETES The relationship between COVID-19 and diabetes is bidirectional. On the one hand, individuals with diabetes are at higher risk than the general population for severe health complications and/or death due to COVID-19. On the other hand, evidence is emerging which suggests that COVID-19 can promote the development of new-onset diabetes. According to the Center for Disease Control and Prevention, adults of any age with type 2 diabetes mellitus are at, "increased risk of severe illness from the virus that causes COVID-19" and adults of any age with type 1 diabetes, "might be at an increased risk for severe illness from the virus that causes COVID-19" (CDC, 2020). It's important to note that this recommendation does not mean that individuals with diabetes are more likely to become infected with COVID-19, but rather that of individuals already infected with COVID-19 those with diabetes are more likely to develop severe complications as a result of the virus than those without diabetes. There are a number of potential biological reasons for this disparity. For one thing, diabetes is associated with a number of other comorbidities that increase the likelihood of COVID-19 complications. These comorbidities include old age, hypertension, cardiovascular disease, and obesity. Furthermore, it has been hypothesized that a dysregulated inflammatory innate and adaptive immune response may occur in response to COVID-19 in patients with diabetes and this impaired response may lead to system wide tissue damage along with respiratory and multiorgan failure. Moreover, provided that low-grade chronic inflammation

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â&#x20AC;&#x153;Diabetes represents an important biological connection between EDCs, HIV/AIDs, and Covid-19 as it demonstrates how all three conditions are related via their effects on both metabolism and immune system function. More specifically, exposure to EDCs can influence the development of diabetes, people living with HIV/AIDs are more likely to have type 2 diabetes than the general population, and individuals with diabetes are at risk of developing severe complications from Covid-19.â&#x20AC;?

is a symptom of diabetes and that inflammation can promote a cytokine storm, individuals with diabetes are more likely to experience a COVID-19 induced cytokine storm than individuals without diabetes (Apicella et al., 2020). As previously discussed, a cytokine storm is a severe immune reaction characterized by excessive release of pro-inflammatory cytokines. Cytokine storms can lead to multiple organ failure and can be life-threatening in some cases (National Cancer Institute, 2020). Finally, given that COVID-19 binds to ACE2 receptors which are expressed in pancreatic beta-cells among other locations, infection with COVID-19 can impair insulin secretory capacity and consequently promote the development of diabetic ketoacidosis and/or hyperglycemic hyperosmolar syndrome both of which represent significant health complications for diabetic individuals. The impairment of beta-cell function due to COVID-19 is also the main reason why infection with COVID-19 could possibly lead to the development of diabetes in previously non-diabetic individuals though more research is needed (Apicella et al., 2020). Given the biological relationships between COVID-19 and diabetes, it's clear why diabetes represents a significant risk factor when it comes to COVID-19 and why COVID-19 may contribute to the development of new-onset diabetes in non-diabetic individuals.

PUTTING IT ALL TOGETHER Diabetes remains an important health issue in the United States and throughout the world and it represents a significant link between the three health issues discussed in this project. Specifically, diabetes shows how EDCs, HIV/AIDs, and COVID-19 are all related in that each can influence both metabolism and immune system function. In this way, the three health conditions can interact with each other in varying ways to influence health outcomes as discussed throughout this project. All things considered, this case study of diabetes demonstrates how even from a strictly biological perspective, health and disease do not exist in isolation. That is, the various biological links between these seemingly unrelated health conditions show how every health issue exists within a larger biological context and this becomes even more complex when one begins to consider other factors such as history and social determinants as we attempt to do throughout this project. That being said, the importance of employing a holistic approach when evaluating any and all health conditions cannot be overstated.

“The various biological links between these seemingly unrelated health conditions show how every health issue exists within a larger biological context.”

Adobe Stock, 2019

SOURCES Adobe Stock. (2019, May 30). [Interconnectedness]. Retrieved from https://www.callcentrehelper.com/interconnectedness-solution-own-problem-142672.htm Almekinder, E. (2016). [Insulin secretion in pancreatic beta cells]. Retrieved from https://www.thediabetescouncil.com/beta-cells-diabetes/ Apicella, M., Campopiano, M. C., Mantuano, M., Mazoni, L., Coppelli, A., & Del Prato, S. (2020). COVID-19 in people with diabetes: Understanding the reasons for worse outcomes. The Lancet Diabetes & Endocrinology, 8(9), 782–792. https://doi.org/10.1016/S2213-8587(20)30238-2 CDC. (2020, February 11). Coronavirus Disease 2019 (COVID-19). Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019-ncov/need-extra precautions/ people-with-medical conditions.html Davis, K. (2020, November 4). [Covid-19 and diabetes]. Retrieved from https://www.medicalnewstoday.com/articles/covid-19-and-diabetes Definition of cytokine storm—NCI Dictionary of Cancer Terms—National Cancer Institute (nciglobal,ncienterprise). (2011, February 2). [NciAppModulePage]. https://www.cancer.gov/ publications/dictionaries/cancer-terms/def/cytokine-storm Diabetes. (2020, October 30). Retrieved November 30, 2020, from https://www.mayoclinic.org/diseases-conditions/diabetes/symptoms-causes/syc-20371444 Duncan, A. (2015). Chapter 21—Dietary Interventions in People with HIV and Diabetes. In R. R. Watson (Ed.), Health of HIV Infected People (pp. 389–399). Academic Press. https://doi. org/10.1016/B978-0-12- 800769-3.00021-4 Hernandez-Romieu, A. C., Garg, S., Rosenberg, E. S., Thompson-Paul, A. M., & Skarbinski, J. (2017). Is diabetes prevalence higher among HIV-infected individuals compared with the general population? Evidence from MMP and NHANES 2009–2010. BMJ Open Diabetes Research & Care, 5(1). https://doi.org/10.1136/bmjdrc-2016-000304 James-Todd, T. M., Chiu, Y.-H., & Zota, A. R. (2016). Racial/ethnic disparities in environmental endocrine disrupting chemicals and women’s reproductive health outcomes: Epidemiological examples across the life course. Current Epidemiology Reports, 3(2), 161–180. https://doi.org/10.1007/s40471-016-0073-9 Lind, P. M., & Lind, L. (2018). Endocrine-disrupting chemicals and risk of diabetes: An evidence-based review. Diabetologia, 61(7), 1495–1502. https://doi.org/10.1007/s00125-018-46213 Murphy, C. S., & McKay, G. A. (2013). HIV and diabetes. Diabetes Management, 3(6), 495–503. https://doi.org/10.2217/dmt.13.52 National Diabetes Statistics Report, 2020. (2020, February 11). Retrieved November 30, 2020, from https://www.cdc.gov/diabetes/library/features/diabetes-stat-report.html Sarkar, S., & Brown, T. T. (2000). Diabetes in People Living with HIV. In K. R. Feingold, B. Anawalt, A. Boyce, G. Chrousos, W. W. de Herder, K. Dungan, A. Grossman, J. M. Hershman, H. J. Hofland, G. Kaltsas, C. Koch, P. Kopp, M. Korbonits, R. McLachlan, J. E. Morley, M. New, J. Purnell, F. Singer, C. A. Stratakis, … D. P. Wilson (Eds.), Endotext. MDText.com, Inc. http://www.ncbi.nlm.nih.gov/books/NBK545886/ Spanakis, E. K., & Golden, S. H. (2013). Race/Ethnic Difference in Diabetes and Diabetic Complications. Current Diabetes Reports, 13(6). https://doi.org/10.1007/s11892-013-0421-9 Stock.adobe.com. (2020, February 4). [Blood glucose monitoring]. Retrieved from https://news.yale.edu/2020/02/04/studies-suggest-new-path-reversing-type-2-diabetes-and-liverfibrosis Type 1 Diabetes. (2020, March 11). Retrieved November 30, 2020, from https://www.cdc.gov/diabetes/basics/type1.html Type 2 diabetes. (2020, August 26). Retrieved November 30, 2020, from https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/symptoms-causes/syc-20351193

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in/visible illnesses: social determinants

bearing an unequal burden

Outstretched hands hold out red ribbons, symbolic of HIV/AIDS> Shutterstcok Images

by sarah sullivan

Examining the social determinants of health in the AIDS epidemic, COVID-19 pandemic, and effects of endocrine disrupting chemicals in the United States. In the United States, roughly 1 in 2 Black men who have sex with men (MSM) and 1 in 4 Latino MSM will be diagnosed with HIV, compared to only 1 in 11 white MSM (CDC, 2016). As the COVID-19 pandemic grows at unprecedented rates with no signs of slowing down, Black Americans are nearly three times as likely to be infected with COVID-19 and almost twice as likely to die from the virus than white Americans (Johns Hopkins Center for Health Equity, 2020), and a 2018 study on racial disparities in disease burden due to exposure to EDCs found that Black and Latino populations bear a notably higher share of financial costs of EDC exposure-related diseases than nonHispanic white populations (Attina et al., 2018). For most healthcare professionals, these statistics are far from surprising. History is, if nothing else, at least consistent. For past epidemics and public health crises, disparities tend to follow differences in a populationâ&#x20AC;&#x2122;s social determinants of health: access to education and healthcare; community and social contexts (such as race, ethnicity, gender and sexual orientation, and resulting discrimination); economic stability; and their neighborhood and environment (such as housing quality, access to healthy food, safe water, transportation, and exposure to pollutants) (CDC, 2020). By examining each social factor that creates health disparities independently and through symptomatic reports of HIV, COVID-19, and diseases caused by exposure to EDCs, scientists and

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medical professionals can begin to deconstruct the institutional systems driving these unequal burdens instead of just treating their consequences.

HIV/AIDS: From the start of the epidemic, the burden of HIV has never been shared equally. Originally labelled gay-related immunodeficiency (GRID) by researchers, HIV/AIDS has traditionally targeted MSM due to the methods by which HIV is transmitted, not inherent biological differences between gay and straight men. Nearly 40 years after the first clusters of HIV-related Kaposiâ&#x20AC;&#x2122;s Sarcoma and pneumonia were discovered in the United States, HIV transmission is still concentrated in sexual minorities and communities of color despite overall declining rates of infection. In 2018, 69% of all new HIV diagnoses were found in MSM, with Black MSM accounting for 25% and Latino MSM accounting for 20% of the total diagnoses across all sexualities. Additionally, transgender individuals and people who inject drugs continue to be overrepresented in HIV diagnoses rates across all regions of the US (HIV.gov, 2020). Most Americans living with HIV tend to reside in large coastal urban areas or throughout the southeastern area, particularly in rural areas with poor access to testing or treatment. In 2011, the CDC reported that HIV is almost unilaterally concentrated in low-income communities in both urban and rural areas as well as among those who are unemployed and possess less than a high school education (Pellowski et al., 2013). 44% of all new HIV infections were found in African Americans, despite the fact that African Americans constitute only 14% of the total US population. Despite their

Individuals line up to get tested fof COVID-19 in Calexico, CA., a town near the U.S.-Mexico Border. Mario Tama/Getty Images

heightened risk of exposure to HIV, Black Americans tend to be less aware of their positive status, with roughly 91% of Black MSM who tested positive previously unaware of their status in comparison to only 60% of white MSM. In the southern United States, legal policies such as the unavailability of Medicaid and low health insurance rates drive an average HIV prevalence well over three times as high as the national rate (Sutton et al., 2017). Despite innovations in ARTs and preventative medication such as PrEP and PEP, lack of access to care continues to prevent an equal distribution of these treatments. HIV transmission follows a largely cyclical pattern: institutional racism, socioeconomic inequality, and residential segregation tend to concentrate Black and Latino populations in lower-income communities with poor access to health education and resources, resulting in a higher prevalence of HIV within their social networks, and thus creating a positive feedback loop of increasing transmission rates. Homophobia and stigma surrounding sexual practices underscore each of these factors, discouraging regular testing and open discussion of potential exposures to STDs out of fear of discrimination or social ostracization (Earnshaw et al., 2013).

COVID-19: Nearly all race-based reporting of COVID-19 related morbidity statistics have shown that Black Americans and other communities of color are facing an unequal burden of the coronavirus pandemic. In Louisiana, for example, early reports showed that Black Americans made up 70% of all COVID-19 deaths despite only accounting for 32% of the population (Louis-Jean et al., 2020). This pattern of inequality is seen repeatedly across nearly every geographic region in the US due to underlying disadvantages in access to proper medical care. African Americans are also more likely to reside in overpopulated areas and work in essential, minimum wage jobs such as in factories, public transportation, retail, or prisons that prohibit adequate social distancing measures. Furthermore, the psychological and emotional stresses of institutional racism may play a role in Black Americans vulnerability to COVID-19. Stress due to discrimination may increase the likelihood of high blood pressure, a pre-existing condition that heightens an individual’s risk to more severe COVID-19 symptoms, or overt racism – such as George Floyd’s homicide due to cardiopulmonary arrest caused by law enforcement after being diagnosed with COVID-19 – may increase mortality rates as well (Louis-Jean et al., 2020).

Among the 42 states reporting data for Hispanic Americans, COVID-19 rates for Hispanics were over two times higher in 30 states and over four times higher in eight more. Differences in incidence rates can be largely attributed to their overrepresentation in essential jobs with lower wages. Crowded housing and transportation, poor social distancing measures, poor public health education, and nearly nonexistent access to healthcare and health Despite innovations in insurance has caused ARTs and preventative COVID-19 rates to d i s p r o p o r t i o n a t e l y medication such as PrEP skyrocket among and PEP, lack of access to migrant Latino care continues to prevent farmworkers in the United States (Quandt et an equal distribution of al., 2020). these treatments. In a population with considerably less visibility, preliminary research from 23 states has shown that COVID-19 incidence is around 3.5 times higher for Native Americans than for white Americans (Hatcher et al., 2020). Though research within Indigenous communities on COVID-19 has been limited, Native Americans have long-since born the greatest burden of health-based inequalities while receiving some of the least medical attention and health resources out of all minority groups (Curtice & Choo, 2020). Systemic underreporting of health events stalls outside medical assistance, resulting in decreased availability of personal protective equipment, vital medical equipment such as ventilators, and the necessary medication and testing to mitigate the spread of COVID-19 within Indigenous communities.

EDCs:

A woman recieves a mammogram to detect breast cancer. Wikimedia Commons

Though it is more difficult to track the incidence rates of EDC exposure than HIV or COVID-19 infections, racial and other social determinants of health play a definitive role in adverse health outcomes attributed to EDCs. High rates of non-communicable diseases among ethnic minorities correspond with a higher likelihood to reside in low-income and fenceline communities with greater exposure to environmental chemical pollutants that have been hypothesized to cause those same illnesses. African American women are more likely to be diagnosed and die from breast cancer than white women, while exposure to EDCs such as polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) are linked to IN/VISIBLE

higher incidence rates of breast cancer (Brody et al., 2009). Numerous studies have found a positive correlation between unequal exposures to EDCs across ethnic groups, and a 2018 study on the disparities in environmental exposures to EDCs and diabetes risk in minority populations linked high exposure rates to BPA, PCBs, and phthalates among African American and Latino populations to increased diabetes diagnoses, especially within low-income communities (Ruiz et al., 2018).

UNEQUAL BURDENS: When examining differences in incidence rates of disease among different populations, it is crucial to not attribute statistical disparities to racial essentialism or biological differences between minority groups. Black Americans are not more likely to develop diabetes because they are inherently less healthy, but because they may live in areas with greater exposure to EDCs such as PCBs or air pollutants or use beauty products containing phthalates marketed towards women of color. Black and Latino populations may not be likely to be infected with COVID-19 because of their social habits but rather may be more likely to work in high-risk essential jobs, use public transportation, or live in more crowded housing due to socioeconomic differences caused by underlying systems of hierarchical racial oppression. And of course, gay men are not biologically wired to be more susceptible to HIV, HIV just happens to be more transmittible in male-to-male sexual contact. As we have seen from a statistical analysis of transmission and diagnoses rates, the same social determinants of health tend to drive the same disparities in incidences of HIV/AIDS, COVID-19, and EDC exposure-related illnesses. Without deconstructing the institutional systems of oppression and inequality that create these differences, disenfranchised and minority populations will always bear the greatest, unequal burden of disease.

Bebeto Matthews/Associated Press, 2020

SOURCES: Center for Disease Control National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. (2016, February 23). Half of black gay men and a quarter of Latino gay men project ed to be diagnosed within their lifetime. HIV.gov. https://www.hiv.gov/blog/half-of-black-gay-men-and-a-quarter-of-latino-gay-men-projected-to-be-diagnosed-within-theirlifetime Johns Hopkins Center for Health Equity. (2020, August 13) COVID-19 By the Numbers. The State of Black America. (https://nul.org/state-of-black-america Attina, T. M., Malits, J., Naidu, M., & Trasande, L. (2019). Racial/ethnic disparities in disease burden and costs related to exposure to endocrine-disrupting chemicals in the United States: an exploratory analysis. Journal of clinical epidemiology, 108, 34–43. https://doi.org/10.1016/j.jclinepi.2018.11.024 Centers for Disease Control and Prevention. (2020, August 19). Social Determinants of Health: Know What Affects Health. https://www.cdc.gov/socialdeterminants/index.htm HIV.gov. (2020, June 30). Overview: Data & Trends: U.S. Statistics. https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics Pellowski, J. A., Kalichman, S. C., Matthews, K. A., & Adler, N. (2013). A pandemic of the poor: social disadvantage and the U.S. HIV epidemic. The American psychologist, 68(4), 197–209. https://doi.org/10.1037/a0032694 Sutton, M. Y., Gray, S. C., Elmore, K., & Gaul, Z. (2017). Social Determinants of HIV Disparities in the Southern United States and in Counties with Historically Black Colleges and Univer sities (HBCUs), 2013-2014. PloS one, 12(1), e0170714. https://doi.org/10.1371/journal.pone.0170714 Earnshaw, V. A., Bogart, L. M., Dovidio, J. F., & Williams, D. R. (2013). Stigma and racial/ethnic HIV disparities: moving toward resilience. The American psychologist, 68(4), 225–236. https:// doi.org/10.1037/a0032705 Louis-Jean, J., Cenat, K., Njoku, C. V., Angelo, J., & Sanon, D. (2020). Coronavirus (COVID-19) and Racial Disparities: a Perspective Analysis. Journal of racial and ethnic health disparities, 7(6), 1039–1045. https://doi.org/10.1007/s40615-020-00879-4 Quandt, S. A., LaMonto, N. J., Mora, D. C., Talton, J. W., Laurienti, P. J., & Arcury, T. A. (2020). COVID-19 Pandemic among Latinx Farmworker and Nonfarmworker Families in North Car olina: Knowledge, Risk Perceptions, and Preventive Behaviors. International journal of environmental research and public health, 17(16), 5786. https://doi.org/10.3390/ijerph17165786 Hatcher, S. M., Agnew-Brune, C., Anderson, M., Zambrano, L. D., Rose, C. E., Jim, M., A., Baugher, A., Liu, G. S., Patel, S. V., Evans, M. E., Pindyck, T., Dubray, C. L., Rainey, J. J., Chen, J., Sad owski, C., Winglee, K., Penman-Aguilar, A., Dixit, A., Claw, E., Parshall, C., … McCollum, J. (2020). COVID-19 Among American Indian and Alaska Native Persons - 23 States, January 31-July 3, 2020. MMWR. Morbidity and mortality weekly report, 69(34), 1166–1169. https://doi.org/10.15585/mmwr.mm6934e1 Curtice, K., & Choo, E. (2020). Indigenous populations: left behind in the COVID-19 response. Lancet (London, England), 395(10239), 1753. https://doi.org/10.1016/S0140-6736(20)31242-3 Brody, J. G., Morello-Frosch, R., Zota, A., Brown, P., Pérez, C., & Rudel, R. A. (2009). Linking exposure assessment science with policy objectives for environmental justice and breast cancer advocacy: the northern California household exposure study. American journal of public health, 99 Suppl 3(Suppl 3), S600–S609. https://doi.org/10.2105/AJPH.2008.149088 Ruiz, D., Becerra, M., Jagai, J. S., Ard, K., & Sargis, R. M. (2018). Disparities in Environmental Exposures to Endocrine-Disrupting Chemicals and Diabetes Risk in Vulnerable Populations. Diabetes care, 41(1), 193–205. https://doi.org/10.2337/dc16-2765

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in/visible illnesses: social determinants

ECONOMICS AND INEQUITIES THE EFFECTS OF EDCS, COVID, AND HIV/AIDS ON ACCESS TO HEALTHCARE BY DRAKE HIPE When comparing EDCs to COVID & HIV, one observation stands out: health care is inaccessible—big business and pharmaceutical industries are profiting off of consumerism, regulations, and inaccessibility of the general public. Social determinants—which can be used to predict an individual’s ability to access healthcare and necessary medical treatments—for EDCs, COVID, and HIV/ AIDS have already been discussed extensively within this magazine. Oftentimes, access to quality and affordable care can be limited by barriers such as geography, psychosocial implications, and even socioeconomic status.

Due to medical limitations there currently are no cures for either EDC associated adverse effects such as diabetes, COVID, or HIV/AIDS. However, preventing infection across COVID, HIV/AIDS, and EDCs can help ease financial stress on communities and work towards avoiding spending significant funds in the first place. Avoiding a single HIV infection can save individuals over $220,000 during the course of their lifetime (Schackman et al., 2015). Assuming similarities between COVID and EDCs, preventing COVID infection or working on alleviating or addressing social determinants of EDCs can prevent

individuals and communities from expensive medical treatment costs, especially in a health care system that caters towards big business and pharmaceutical companies rather than patients that need the care. Utilizing an interdisciplinary approach that calls upon knowledge, experiences, and narratives, policy makers, medical providers, industry representatives, scientific experts, and even the general public can help address the roots of the inequities to care and even help prevent them in the first place. Endocrine disrupting chemicals come in two forms: they can be naturally-occuring

Adobe Stock Photo, 2020

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or created synthetically. Exposure to EDCs, especially in prolonged low-dose exposure, can create adverse side effects such as reproductive health issues and problems in development. According to a table from The Endocrine Society’s Introduction to Endocrine Disrupting Chemicals (EDCs), some known EDCs and their uses include pesticides (DDT), children’s products (lead), food contact materials (BPA, phenol), electronics and building materials (brominated , personal care products and medical tubing (phthalates), antibacterials (triclosan), and textiles and clothing (perfluorochemicals). With thousands of potential EDCs within over 85,000 different manufactured chemicals, this list is not a complete representation of all the numerous products and industrial processes that may include EDCs. The variety in products and processes give rise to a variety of EDC exposure routes such as food consumption, inhalation, or bodily transfers (mother to fetus across placenta or mother to infant via lactation). Endocrine disruptors have become widespread and pose potentially serious consequences to the hormonal systems, yet they still remain in the environment and in everyday products. A major reason for their continuous

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“EDCS ARE A GLOBAL AND UBIQUITOUS PROBLEM. EXPOSURE OCCURS AT HOME, IN THE OFFICE, ON THE FARM, IN THE AIR WE BREATHE, THE FOOD WE EAT, AND THE WATER WE DRINK. OF THE HUNDREDS OF THOUSANDS OF MANUFACTURED CHEMICALS, IT IS ESTIMATED THAT ABOUT 1000 MAY HAVE ENDOCRINEACTING PROPERTIES.” - THE ENDOCRINE SOCIETY presence is the influence of big business and industry, ultimately affecting access and costs to equitable health care. The thousands of manufactured chemicals that potentially may serve as EDCs are associated with several disabilities and diseases. In fact, treating these disabilities and diseases identified by exposure-response relations is rather costly, costing the U.S. roughly $340 billion dollars in 2010 alone (Merrill). Many of the adverse health outcomes associated with endocrine disruptors are also correlated to HIV and

COVID. Though the extent of EDCs effects aren’t fully understood, the damage is still there and costs are often driven by EDCs such phthalates from plastics as well as pesticides. Healthcare for HIV, specifically treatment drugs, remains expensive for PLWHA. As of 2016, the HIV drug market was worth over $24 billion, much of it representing sales of antiviral agents and antiinfectives, and it is only projected to grow higher in future years (Gubernick, 2016). Advances and breakthroughs in therapies and medicine such as AZT and antiretroviral treatment (ART) do not come with cheaper price tags. In 2012, US average wholesale prices for initial ART regimens, a mainstay for everyone who is living with HIV, ranged from approximately $25,000 to over $35,000. By 2018, the initial ART regime had risen to ranges of $36,000 to $48,000 displaying an increase of around 34%—much faster than the rate of inflation. In clinical settings, average annual costs for these treatments rose from approximately $26,000 to just under $40,000 at an increase of about 53% (Shaw, 2020). It should never be the patients’ responsibility to choose between saving money and getting equitable, quality care,

which is indicative of an inherently flawed medical system. Even with several more options for antiretroviral treatment, accessibility has not increased with it as the United States leads the world in having the highest costs for ART. In conjunction with social determinants and socioeconomic status, this may be problematic in ensuring quality healthcare over the entire United States population for PLWHA. The high costs for COVID treatments are inaccessible when there is a shortage of medical beds, staff, and other equipment needed to handle the COVID pandemic. This leaves many Americans hesitant to get tested or head to the emergency room. Testing alone can range from $20 to $850 (Wapner, 2020). The unprecedented pandemic in COVID has psychosocial implications on getting proper treatments. Again like HIV/AIDS and EDCs, this also makes it difficult for marginalized communities and people with low socioeconomic status to be able to afford or cope with COVID-19. The medical system as it stands revealed its deep flaws in addressing health disparities in the United States. COVID-19 disproportionately affected those with marginalized identities or low socioeconomic status. Much like HIV/AIDS and EDCs, the people needing COVID treatments are at a disadvantage when it comes to affording or even accessing necessary health care treatments. High medical costs and drug treatment prices are controlled by big business and industry, leaving many with two choices: find a way to afford their care or suffer through consequences of not seeking out treatment. Regardless, these consequences plague those exposed to EDCs, HIV, and COVID-19 and serve as barriers to equitable healthcare. This only serves to re-emphasize the need for an interdisciplinary approach as we tackle roots found in their intersectionality.

SOURCES: Chenneville, T., Gabbidon, K., Hanson, P., & Holyfield, C. (2020). The Impact of COVID-19 on HIV Treatment and Research: A Call to Action. International Journal of Environmental Research and Public Health, 17(12), 4548. MDPI AG. Retrieved from http://dx.doi.org/10.3390 ijerph17124548 Gore, A.C., Crews, D., Doan, L.L., Merrill, M.L., Patisaul, H., & Zota, A. Introduction to Endocrine Disrupting Chemicals (EDCs): A Guide for Public Interest Organizations and Policy-Makers. The Endocrine Soceity. (2014 December). https://www. endocrine.org/-/media/endosociety/files/advocacy-and-outreach/importantdocuments/introduction-to-endocrine-disrupting-chemicals.pdf Gubernick, S., Félix, N., Lee, D. et al. The HIV therapy market. Nat Rev Drug Discov 15, 451–452 (2016). https://doi.org/10.1038/nrd.2016.69 HIV.gov. Overview Data & Trends: U.S Statistics. HIV.gov via CDC. (2018). https://www. hiv.gov/hiv-basics/overview/data-and-trends/statistics Merrill, M.A. The economic legacy of endocrine-disrupting chemicals. The Lancet: Diabetes and Endocrinology. (2016). https://doi.org/10.1016/S22138587(16)302790 Schackman, B. R., Fleishman, J. A., Su, A. E., Berkowitz, B. K., Moore, R. D., Walensky, R. P., Becker, J. E., Voss, C., Paltiel, A. D., Weinstein, M. C., Freedberg, K. A., Gebo, K. A., & Losina, E. (2015). The lifetime medical cost savings from preventing HIV in the United States. Medical care, 53(4), 293–301. https://doi.org/10.1097/ MLR.0000000000000308 Shaw, Maggie. What IS the True Cost of the High Price of ART? The American Journal of Managed Care. (2020). https://www.ajmc.com/view/what-is-the-true-cost-of-thehigh-price-of-art Wapner J. Covid-19: Medical expenses leave many Americans deep in debt. BMJ. (2020, Aug 14); 370:m3097. doi: 10.1136/bmj.m3097. PMID: 32816817. Adobe Stock Photo, 2016

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in/visible illnesses: social determinants

hiv: activism, drugs, and evolved understandings THE FIRST, CONTENTIOUS, LANDMARK HIV DRUG: AZIDOTHYMIDINE, OR AZT

by sheel shah

In the anxious years after the onset of the HIV epidemic, the search for effective treatment modalities was rampant; millions were at the risk of fatal consequences, and infections were spreading rapidly. A defining feature of this race, however, was the contentions surrounding it: HIV was termed “GRID” for gay-related infectious disease, and its disproportionate impact on the queer community somehow overshadowed its significance. Nonetheless, public pressure (such as by political groups like ACT UP, covered next) and social activism helped draw attention to this issue and spur the race toward effective treatment. New York Historical Society

PLACING HIV ACTIVISM IN CONTEXT This article strives to detail the early pharmacological movements and activism surrounding the height of the HIV/AIDS pandemic within the United States; yet by doing so it shed lights on a seemingly more implicit occurrence: the lack of activism surrounding EDCs and perhaps even COVID-19. This last point is definitely worth mentioning, as it begs the question: what led to the activism surrounding the HIV/AIDS movement in particular? Perhaps, it was due to HIV’s disproportionate impact on marginalized communities, particularly the queer community. Or perhaps it was the profound lack of action taken upon its emergence—costing the lives of millions— because stigma, negligence, and hate overshadowed the significance of human life rightfully fueling unrest. Or perhaps it was the very magnitude and severity of HIV’s etiology, progressing from a benign fever to a bed-ridden condition of seeming ‘exploitation’ from even relatively harmless pathogens. Whatever the reasons, this inspires a more uplifting thought—how can we mobilize social activism, support, and awareness for “invisible” phenomena like the influence of endocrine disrupting chemicals (hidden in everything from sunscreen to plastics) and the global COVID-19 pandemic (which has seemingly divided Americans who argue in favor of public health from those who value individual freedom and autonomy)? Understanding and analyzing these parallels will help contextualize the activism surrounding the HIV/AIDS movement as we progress through this article.

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Amid researched treatment modalities was AZT—a compound initially developed in the 1960s in an effort to thwart cancer by interfering with cell replication. Yet despite its failed influence on these cancerous cells, it was re-purposed by the pharmaceutical company Burroughs Wellcome, who proved it was effective in thwarting viral activity in pre-clinical models (Park, 2017). Despite the perceived significance of this finding, this wasn’t enough: research had to prove its safety, generalizable efficacy, and

quantifiable success in human populations. While such processes were important, their projected time span was around 8-10 years—a duration that would prove catastrophic for the thousands already living with the virus (Park, 2017). Under enormous public pressure, the Food and Drug Administration (FDA) sped-up the review process for AZT; an action that has since come to light as incredibly contentious (Park, 2017; FDA, 2019). In clinical trials immediately predating its approval, AZT was shown to have severe side effects, including gastrointestinal damage, immune system damage, nausea, diarrhea, vomiting and migraines. That said, in 300 patients diagnosed with AIDS (important that it was already at this late stage of HIV infection), AZT was tested in a randomized, placebo-controlled trial; one group was given a placebo and another was administered AZT. In 16 weeks, the group administered AZT only had 1 death; the other had 19 (Park, 2017; FDA, 2019). The shocking disparity led to the halting of the trial and the push for AZTs emergency, immediate approval; it was deemed “relatively safe” as the perceived risks outweighed the then observed consequences, and the reasoning was that it would be unethical to hold such a promising treatment modality from the affected population. Just 20 months thereafter, on March 19, 1987, the FDA approved AZT as a “breakthrough” medication—there was

seemingly light at the end of the tunnel for those living with HIV (Park, 2017; FDA, 2019). Despite this data, the study remains contentious. Reports soon surfaced detailing that physicians were not adopting uniform treatment regimens; that some patients were being provided with blood transfusions to boost their immune response; and still others were supposedly “pooling pills” to ameliorate their chances of receiving some of the drug rather than simply placebos (Park, 2017). In other words, the study and its data was later found to be incredibly dubious. While this would have been traditionally unacceptable in accordance with the FDAs 8-10-year review process, AZTs expedited review nature overlooked these discrepancies; the result was a drug that had been inadequately tested yet still adopted as a first-line treatment modality, which soon proved to be incredibly ineffective. Those living with the virus not only suffered the horrific consequences associated with AZT—but most also realized that HIV had become resistant to this treatment modality soon after its administration (Park, 2017; FDA, 2019). The result was seemingly worse than before: most who received treatment not only suffered the fatal consequences associated with AIDS, but also those associated with AZT and HIV now resistant to this antiretroviral medication—a phenomenon described by some as “unbearable” (Park, 2017).

While antiretroviral therapy has since evolved to target HIV at various stages of its replication cycle (as previously discussed), other treatment measures are aimed at early diagnosis (especially for pediatric patients who acquired HIV through an affected mother), this was clearly not always the case. Current measures are focused on early diagnosis and treatment— capable of reducing HIV to undetectable and non-contagious levels in most patients—yet an understanding of the history surrounding HIV’s first treatment mechanisms is crucial nonetheless; it demonstrates the bioethical limitations of disease treatment, and the significance of testing the safety, efficacy, and generalizability of supposedly successful treatment modalities. These refined understandings of scientific practice and history afford crucial lessons in the era of COVID-19: how reputable are data published directly by pharmaceutical company and how do we eliminate the confounds posed by corporate bias and potentially skewed results? What is more effective—having a vaccine or thoroughly testing its safety? How do we go about finding a balance between these two idealistic conditions? How do we eliminate the monetization of a COVID-19 vaccine? How relevant are endocrine-disrupting effects of a potential vaccine, and how would we test for such long-term endpoints in such a short, urgent time-frame? The era of premature HIV treatment modalities may very well be over, but another chapter pertaining to COVID-19 is only beginning, and it is crucial we learn from our past mistakes; it is crucial that we find an effective balance between safety and public health.

“Just 20 months thereafter, on March 19, 1987, the FDA approved AZT as a “breakthrough” medication—there was seemingly light at the end of the tunnel for those living with HIV.” IN/VISIBLE

AIDS COALTION TO UNLEASH POWER (ACT UP): ONE OF MANY ACTIVIST GROUPS ADVANCING HIV/AIDS POLICY Amid the recent activism surrounding the Black Lives Matter movement and ongoing pleas for eradicating systemic inequity and racial injustice, it is worth mentioning the success of social activism at the height of the HIV/AIDS epidemic; it demonstrates the success of improving awareness, fighting for change, and making strides toward equality. ACT UP (which reclaims the narrative and rhetoric surrounding the upside down pink triangle used to mark “gays” in Nazi concentration camps through its upright pink triangle logo and slogan “SILENCE=DEATH”) is an international, grassroots, political and social activist group that pushed (and continues to push) for change through advocacy, research, policy, and direct action; these efforts are tailored specifically toward improving the lives and rights of those living with HIV (ACT UP, 2012; Aizenman, 2019). Amid its most salient goals were increasing the accessibility, coverage, and availability of HIV/AIDS treatment; eliminating the stigma and empowering those living with HIV/AIDS; and using activism as a form of enacting more inclusive, just, and fair policies at institutional, corporate, and governmental levels (ACT UP, 2012; Aizenman, 2019). A direct excerpt from ACT UP’s website detailing the organizations/governments against which it has protested is listed below; the excerpt details the widespread scope of the organization’s endeavors, and its success in lobbying against seemingly “impenetrable” regulatory bodies and governments to enact positive change (ACT UP, 2012). Disclaimer: the information below is directly from the ACT UP website, and is not original work. “Wall St pharmaceutical companies: for profiteering from people with AIDS by charging astronomically high prices for AIDS medicine FDA (Food and Drug Administration): for its years-long drug approval process, resulting in the deaths of thousands due to lack of access to potentially life-saving drugs CDC (Center for Disease Control): for its narrow definition of AIDS, which did not include infections that affect women and injection drug users NIH (National Institutes of Health): for its lack of prioritizing diverse types of AIDS treatments and for underrepresenting women and people of color in clinical trials President Bush Sr: for spending a billion dollars a day on the Gulf War after claiming there was little money to increase AIDS spending President Clinton and VP Gore: for refusing to lift the ban on

ACT UP protesters stage a “die-in” outside the FDA. J. Scott Applewhite

needle-exchange funding and for blocking generic production of AIDS drugs by poor countries and inadequate funding of global AIDS. The G8 (richest) countries: (through ACT UP’s alliance with Health Global Access Project and others) for their unwillingness to fund universal global AIDS drug access to all who need it. Mayors Koch and Giuliani, Governor Cuomo Sr: for their inaction and neglect regarding the AIDS crisis and for cuts to local and state AIDS services Health insurance companies: for their refusal to insurance many people with HIV/AIDS and their discriminatory rates for people with HIV/AIDS. Catholic Church: for its opposition to safe sex education in schools and its ineffective demonization of sex, condoms and AIDS.” (ACT UP, 2012)

The above list demonstrates ACT UP’s scope and perhaps the complexities perpetuating the disproportionate health impacts posed by HIV—how its historic stigmatization ties back to not only religion (the “Catholic Church) but to insurance companies, presidential mistreatment, supposedly reputed organizations like the FDA and CDC, and even pharmaceutical companies themselves. Their fights demonstrate perhaps a somber reality of the American healthcare model: it is complex, with multi-conglomerate, governmental, and religious influences that seem almost impossible to fight against. Yet as ACT UP’s success in pushing for parity in HIV/AIDS treatment, diagnosis and action has proven, social activism is not fruitless. Perhaps this glimmer of hope will inspire future activists—fighting for improved sustainability and research on topics ranging from the stigmatization of mental health to endocrine disrupting chemicals and beyond.

SOURCES: ACT UP. (2012). ACT UP Accomplishments and Partial Chronology | ACT UP NY. https://actupny.com/actions/, https://actupny.com/actions/ Aizenman, N. (2019, February 9). How To Demand A Medical Breakthrough: Lessons From The AIDS Fight. NPR. https://www.npr.org/sections/health-shots/2019/02/09/689924838/ how-to-demand-a-medical-breakthrough-lessons-from-the-aids-fight D’Andrea, G., Brisdelli, F., & Bozzi, A. (2008). AZT: an old drug with new perspectives. Current clinical pharmacology, 3(1), 20–37. https://doi.org/10.2174/157488408783329913 FDA. (2019). The History of FDA’s Role in Preventing the Spread of HIV/AIDS. https://www.fda.gov/about-fda/virtual-exhibits-fda-history/history-fdas-role-preventing-spreadhivaids Park, A. (2017, March 19). The Story Behind the First AIDS Drug, Approved 30 Years Ago. Time. https://time.com/4705809/first-aids-drug-azt/

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AP Photo, 2020

concluding remarks Given research limitations and relatively new understandings of COVID-19, EDCs, and HIV/AIDS, it is easy to overlook the significant health and social challenges perpetuated by each of these crises; to forget the complex histories and etiologies linked to each of these conditions; and to lose sight of the impetus for spurring positive change through action and advocacy. This sombre epiphany served as the inspiration for our magazine’s title—in/visible illnesses—rooted in the hope of creating a more transparent, sustainable, and healthy future, one step at a time. While this magazine’s exploration of the interactions and various factors that have influenced the crisis involving EDC exposure, the HIV/AIDS pandemic, and the COVID-19 pandemic represents just a fraction of the diverse factors that influence health, we nevertheless believe that it represents an important first step towards uncovering the interconnected nature of health, illness, and society. Above all else, we hope that this magazine demonstrates the need for an interdisciplinary approach to health and inspires real change. Last but not least we would like to extend our sincerest gratitude to our mentor, Dr. Rensel, who went out of her way to make Society and Genetics 108 as enriching as possible given the challenges posed by the COVID-19 pandemic, while unconditionally supporting us throughout the group project process. Dr. Rensel, we hope you enjoyed reading this magazine as much as we did creating it.

Drake Hipe, Mike Matthews, Sheel Shah, Edward Suarez, and Sarah Sullivan Society & Genetics 108: Fall 2020 IN/VISIBLE