AIDS Breaks Out - History

AIDS Breaks Out - History

(4/21/84) French scientists reported isolating the virus that caused Acquired Immune Deficiency Syndrome (AIDS). In 1984, 7,000 cases of AIDS had been reported in the United States; 3,300 of its victims were dead by the end of the year.

Pandemics That Changed History

In the realm of infectious diseases, a pandemic is the worst case scenario. When an epidemic spreads beyond a country’s borders, that’s when the disease officially becomes a pandemic.

Communicable diseases existed during humankind’s hunter-gatherer days, but the shift to agrarian life 10,000 years ago created communities that made epidemics more possible. Malaria, tuberculosis, leprosy, influenza, smallpox and others first appeared during this period.

READ MORE: See all pandemic coverage here. 

The more civilized humans became, building cities and forging trade routes to connect with other cities, and waging wars with them, the more likely pandemics became. See a timeline below of pandemics that, in ravaging human populations, changed history.

HIV Transmission and the History of HIV/AIDS

Acquired immunodeficiency syndrome (AIDS) is an older term for the symptoms and illness caused by infection with the human immunodeficiency virus (HIV). In the past, doctors referred to AIDS or "full-blown AIDS" as a separate and more serious phase of the infection. With modern treatments, HIV disease is managed as a long-term illness, and the use of "AIDS" to refer to a separate phase is no longer necessary. Therefore, HIV is now referred to as HIV disease or HIV/AIDS. HIV infects many cells in the body, but the most important ones that cause medical illness are the cells of the immune system.

What Causes HIV/AIDS?

HIV may cause a brief illness and rash during the very early phase of infection, and it may mimic many common virus infections like the common cold, influenza, or even mononucleosis. More often, early infection causes no symptoms, and the person infected is not aware. As HIV infects more and more immune cells over time, the immune cells start to decline and the person is not able to fight off infections. The lower the immune cells drop, the more and more unusual infections begin to occur. Eventually, the person seeks medical care, and HIV infection is often diagnosed at this point in HIV disease.

Research has also suggested that long-term infection with HIV causes long-term inflammation that may lead to conditions such as heart disease, diabetes, stroke, and more these conditions are found to occur at younger ages in those infected with HIV than in those who are not. Current health guidelines recommend HIV testing for all teens and adults who are sexually active or are exposed to blood and body fluid products. This is recommended at least once in a lifetime, each time a woman is pregnant, and more frequently if the person has risk factors for becoming infected with HIV.

By discovering HIV infection early, effective treatment can be offered to improve the long-term effectiveness of the treatments, prevent babies from being born with HIV or acquiring it from breastfeeding, prevent spread of infection to others, and reduce inflammation-related conditions like diabetes that may reduce quality of life and life span. Early detection of HIV infection also alerts doctors to screen for other diseases that are acquired in the same ways as HIV and may affect health.


What Is the History and Treatment of HIV/AIDS?

The syndrome caused by HIV was first recognized in the U.S. in the late 1970s. Research has confirmed that HIV evolved from a very similar virus, simian immunodeficiency virus, found in chimpanzees in West Africa. HIV is felt to have mutated and jumped to humans when chimpanzees were hunted for meat. This may have occurred as early as the 1800s, and HIV has slowly spread across the world, spreading faster with globalization and travel in recent times (since the 1980s).

In the late 1980s, the first drug treatment with azidothymidine (AZT) or retrovir, became available for treatment of HIV.

In the mid-1990s, antiretroviral therapy as a combination treatment of HIV infection with at least three medications revolutionized the management of this disease. The disease is much more easily controlled with antiretroviral therapy, and progression to advanced stages is now much less common. Today, HIV/AIDS is treatable by several combinations of medications, in some cases, with one combination pill a day.

What was once considered a "death sentence" is now a treatable chronic illness, much like diabetes or heart disease, as long as the person infected does not miss medication doses and keeps up with medical monitoring and recommendations. People on effective combination treatment for HIV may lead relatively normal and productive lives.


HIV is transmitted by the direct transfer of bodily fluids—such as blood and blood products, semen and other genital secretions, or breast milk—from an infected person to an uninfected person. The primary means of transmission worldwide is sexual contact with an infected individual. HIV frequently is spread among intravenous drug users who share needles or syringes. Prior to the development of screening procedures and heat-treating techniques that destroy HIV in blood products, transmission also occurred through contaminated blood products many people with hemophilia contracted HIV in that way. Today the risk of contracting HIV from a blood transfusion is extremely small. In rare cases transmission to health care workers may occur as a result of an accidental stick by a needle that was used to obtain blood from an infected person.

The virus can be transmitted across the placenta or through the breast milk from mother to infant administration of antiretroviral medications to both the mother and the infant about the time of birth reduces the chance that the child will be infected with HIV (see below HIV and pregnancy). Antiretroviral therapy can reduce the risk of transmission from infected persons to their uninfected sexual partners by some 96 percent when prescribed immediately upon diagnosis. Moreover, if infected persons adhere to antiretroviral therapy over the long term, their HIV viral load can eventually become undetectable, which means that the virus cannot be transmitted by sexual contact this phenomenon is referred to as “ undetectable = untransmittable” (U = U).

Deadly Diseases:

Experts warn a global pandemic will halt humanity as we know it in the next 20 to 30 years. Past epidemics may offer some insight into what the future holds. Here’s a look back at some of them.

Smallpox is caused by the variola virus, which spreads through skin-to-skin contact or contact with bodily fluids. It can also be spread through the air.

In 430 B.C., smallpox killed more than 30,000 people in Athens, Greece, reducing the city’s population by at least 20%.

The Plague of Justinian, which began in 541 and continued on and off for nearly 200 years, killed 50 million people in the Middle East, Asia and the Mediterranean basin, according to some estimates. The plague is caused by bacteria that are spread by rats that were bitten by infected fleas.

What's known as the Great Plague of London actually started in China in 1334 and spread along trade routes, wiping out entire towns. Florence, Italy, lost a third of its 90,000 residents in the first six months. Overall, Europe lost 25 million people.

There were approximately 25 million people living in what is now called Mexico when Hernando Cortes arrived in 1519. A smallpox epidemic killed between 5 and 8 million of the native population in the following two years. Over the next century, less than 2 million would survive this and other communicable diseases brought by European explorers.

Smallpox reached Massachusetts in 1633, brought by settlers from France, Great Britain and the Netherlands. It quickly spread to the Native American population, which had up until now been free of this communicable disease. It’s unclear how many were killed by smallpox, though historians estimate some 20 million may have died after the Europeans landed.

Philadelphia was struck with a yellow fever epidemic in 1793 that killed a 10th of the city's 45,000-person population.

The Modern Plague began in the 1860s and killed more than 12 million people in China, India and Hong Kong. It wasn’t until the 1890s that people figured out how the bacterial infection was being spread and a vaccine was created.

A smallpox epidemic in Boston infected 1,500 people in 1901. There were 270 reported deaths.

The largest plague outbreak in the 20th century occurred in Manchuria between 1910 and 1911. Approximately 60,000 people died. The plague still occasionally causes smaller outbreaks in parts of sub-Saharan Africa.

The great flu pandemic of 1918 and 1919 is estimated to have killed between 30 million and 50 million people worldwide. Among them were 675,000 Americans.

Polio peaked in the US. Nearly 60,000 children were infected and more than 3,000 died. Three years later vaccination began to prevent the communicable disease.

In 1984, scientists identified the human immunodeficiency virus, or HIV, as the cause of AIDS. That same year the deadly disease killed more than 5,500 people in the United States. Today more than 35 million people around the world are living with an HIV infection. More than 25 million people have died of AIDS since the first cases were reported.

Severe Acute Respiratory Syndrome, better known as SARS, was first identified in 2003 in China, though the first case is believed to have occurred in November 2002. By July more than 8,000 cases and 774 deaths had been reported.

The global H1N1 flu pandemic may have killed as many as 575,000 people, though only 18,500 deaths were confirmed. The H1N1 virus is a type of swine flu, which is a respiratory disease of pigs caused by the type A influenza virus.

An epidemic of cholera killed at least 10,000 people in Haiti in 2010 following a deadly earthquake that paralyzed the nation. The outbreak hampered efforts to rebuild. The United Nations would later apologize for initially denying claims that Nepalese peacekeepers brought the deadly disease to the country following the earthquake.

In 2012, approximately 122,000 people worldwide died from the measles, a highly contagious disease caused by a virus. Typhoid fever kills around 216,000 people a year. Tuberculosis, an infectious bacterial disease, killed an estimated 1.3 million in 2012. These are some of the infectious diseases that most concern health officials today.

The 2014 epidemic of Ebola hemorrhagic fever in West Africa was the largest Ebola outbreak on record. The virus killed more than 11,300 people before it was declared over in 2016.

The World Health Organization declared a public health emergency of international concern over Zika virus predicting 3 to 4 million would be infected within a year as it was “spreading explosively” throughout the Americas. Zika is the first mosquito-borne disease to cause a birth defect. The devastating birth defect is microcephaly. The virus is also associated with miscarriage, stillbirth and other neurological deficits. While not deadly in the way other epidemics are, there is a big impact on future generations when fewer children are born because parents are afraid of the virus.

HIV Treatments: A History of Scientific Advance

The introduction of antiviral medications used in combination is among the most important advances in the history of HIV/AIDS treatment. By using more than one drug at a time, combination therapy is able to "pin down" HIV from more than one angle, so that even if one drug fails, another can continue to suppress viral replication. But this advance was a long time in the making, following a historical course from "no therapy" to "monotherapy" and now to "combination therapy." This book excerpt provides a historical overview of advances in the monitoring of treatment progress and the emergence of combination therapy.

In the Beginning

In the summer of 1981, Mortality and Morbidity Weekly Report, published by the U.S. Centers for Disease Control and Prevention (CDC), included two reports about increases in previously rare infections among gay men in the New York and California. "Physicians should be alert for Kaposi's sarcoma, [Pneumocystis carinii] pneumonia, and other opportunistic infections associated with immunosuppression in homosexual men." Thus began a process of medical discovery about Acquired Immunodeficiency Syndrome (AIDS) which continues to the present day.

Although medical progress has often seemed slow in coming, advances in knowledge about AIDS have in many ways actually been swift. Within a year, epidemiological evidence had made clear that the causative agent of AIDS was sexually transmissible, and that it had particularly spread within sexual networks of gay men. Within two years, advances in the then-nascent field of retrovirology enabled researchers at the Pasteur Institute in Paris to isolate the "AIDS virus," which eventually came to be known as the Human Immunodeficiency Virus or HIV.

Further research gradually determined the precise means by which HIV invades the human body. Transmitted from person to person primarily through blood, semen, and vaginal secretions, HIV's principal targets are the very cells of the immune system (particularly CD4+ t-cells and macrophages) which are intended to clear foreign pathogens from the body. After entering a cell of the immune system, the virus begins a relentless process of replication, its sole activity and one which allows for a constant spread to new cells. In the process, the immune system of the host organism can be devastated.

Whereas most viruses retain their genetic information on strands of DNA, retroviruses like HIV employ simpler RNA. The virus's outer coat consists of particular glycoproteins, which can form biochemical bonds with particular proteins (such as CD4) that are found on the surface of some cells, notably those in the immune system. Once bonding occurs, the HIV life cycle requires the insertion of its own genetic material into the host cell and ultimately the use of three important viral enzymes. The first, reverse transcriptase, converts RNA into DNA (a process called "reverse transcription"). The second, integrase, integrates the viral DNA into the human cell's DNA. The third, protease, later cleaves off new copies of the viral proteins, allowing new virus particles to be assembled and enabling these new viruses to leave the cell. These three enzymes are essential to the process of viral replication, and most advances in HIV treatment have come from inhibiting the activity of these enzymes.

From Monotherapy to Combination Therapy

In 1986 the U.S. Food and Drug Administration (FDA) approved the first antiviral drug zidovudine (ZDV AZT) for use in preventing HIV replication by inhibiting the activity of the reverse transcriptase enzyme. AZT is part of a class of drugs formally known as nucleoside analog reverse transcriptase inhibitors. After 1991, several other nucleoside analogs were added to the anti-HIV arsenal, as were a new class of anti-HIV drugs called the non-nucleoside analog reverse transcriptase inhibitors which work in similar ways to the nucleoside analogs but which are more quickly activated once inside the bloodstream. Next to be developed were the class of antiviral drugs known as protease inhibitors, which were distinctly different from the reverse transcriptase inhibitors in that they do not seek to prevent infection of a host cell, but rather to prevent an already infected cell from producing more copies of HIV.

Despite this proliferation of drug options, the standard antiviral therapy for HIV-infected individuals between 1986 and 1995 for the most part remained "monotherapy" or treatment with a single drug. Such drugs appeared to be partly efficacious, although there was a great variation in effectiveness among individuals.

During this period, there were also significant advances in the understanding of how HIV functions in the body. In particular, whereas it was once believed that individuals went into a latency period of ten years or more after their initial infection with HIV, it came to be understood that huge amounts of viral replication continued throughout the entire period of infection, even if an individual was not exhibiting any symptoms of illness. Thus, the onset of symptoms of AIDS is now known to be the result not of a sudden resurgence of a latent virus, but rather of a slow "war of attrition" between HIV and the host immune system, with the latter slowly being whittled away by the former.

The recognition of the persistence of viral replication -- with billions of copies of HIV being produced and destroyed daily -- also made possible a better understanding of the process by which the virus gradually becomes less sensitive to specific antiviral medications, a process known as developing resistance. Such resistance generally occurs when a random mutation during the replication of HIV causes a small genetic change in the virus's RNA, in the process making it less vulnerable to the effects of antiviral drugs. Drug resistance can seriously complicate treatment by rendering drugs less effective or even completely ineffective. Further, once an organism has developed resistance to one drug, it can also become resistant to other drugs in the same class (cross-resistance) or to a number of different drugs (multidrug resistance).

From this perspective, it could be seen that monotherapy against HIV was of limited usefulness because HIV could quickly develop resistance to any one medication. However, the expansion of the number of distinct classes of antiviral medications made possible a shift from monotherapy to combination therapy, in which drugs from two or more classes are used simultaneously. This switch to combination therapy has had dramatic effects because "in essence, combination therapy suffocates mutated forms of HIV before they have a chance to flourish. For example, in a combination of ddI, d4T, and indinavir, a strain of HIV that is naturally resistant to ddI will be kept in check by d4T and indinavir, while a strain of HIV that is resistant to indinavir will be kept in check by d4T and ddI" (Horn 1998). When nucleoside analog drugs, the non-nucleoside analog drugs, and the protease inhibitors are used in concert, these drug combinations are referred to as "highly active antiretroviral therapy" or HAART.

HAART has been prescribed by physicians in a wide variety of combinations, and, over time, convincing evidence has emerged that particular combinations of one protease inhibitor and one or two other drugs can have dramatic effects, reducing the amount of virus in the blood, prompting an increase in the number of CD4+ cells, and leading to improved health and well-being and minimizing the opportunity for new mutations which might create drug-resistant strains of HIV. By the start of 1997, combination therapy had become the standard of care for HIV-infected individuals who have begun to exhibit signs of significant immunosuppression, although no clear cut consensus has emerged about the best time to initiate therapy. This decision must be based on balancing a variety of factors including the length of time since initial infection, current CD4 cell count and viral load, clinical prognosis, side effect profile, and the individual's psychological readiness and motivation to begin and adhere to treatment.

Still Not a Cure

In all, the simultaneous treatment of people with HIV with different classes of antiviral drugs is among the most significant scientific advances in the history of the AIDS epidemic. Five years after its widespread use, combination antiviral therapy has demonstrated enormous potential, eliminating early fears that it would prove to be yet another dead-end in the treatment of HIV infection. On the other hand, however, combination therapies have not yet achieved the most optimistic goals set by scientists, much less the often-hyped claims of the popular media. In particular, the complete elimination, or "eradication," of HIV from an infected individual has never been achieved, and perhaps may never be achieved because HIV has the capacity to remain dormant in certain cells and also to infect difficult-to-reach cells in the central nervous system and other parts of the body. Similarly, antiviral medications have the characteristic of allowing full or partial resistance to develop after even a week of missed medication, irregular use, or incomplete doses, and cross-resistance is very common.

Nonetheless, the overall impact of combination therapies has been overwhelmingly positive. Since the mid-1990s there has been a significant decline in death rates from AIDS in the United States, as well as in new AIDS diagnoses and in hospitalizations for HIV/AIDS-related complications.

This decline in AIDS deaths has been attributed to a variety of causes, including improved treatment of and prophylaxis against opportunistic infections as well as a long-projected epidemiological drop-off as the huge first wave of people infected with HIV in the 1970s or early 1980s died in the early to mid-1990s. However, the introduction of combination therapies has also played a crucial role in this decline. Indeed, combination therapies have brought numerous individuals back from the proverbial "brink of death," restoring many thousands to a semblance of their earlier health and sharply reducing incidence of new HIV-related opportunistic infections and cancers. It appears this trend of declining deaths will continue, though because the advances in treatment have been only available for a relatively short time, no one can say for certain what the long term effects of these treatments will be. Long term use of antivirals may provide a window of opportunity for immune-boosting therapies and perhaps even restoration to normal immunological functioning. On the other hand, continued use of these powerful, toxic medications presents complicating factors of its own -- notably damage to vital organs such as the liver, kidneys and heart.

Another, more subtle, measure of the influence of combination therapies has been made possible by new assays such as the polymerase chain reaction (PCR) and branched DNA (bDNA) that measure viral load, or the number of circulating viral RNA copies in the blood. Previously, clinicians were forced to rely upon the CD4+ cell count as the principal "surrogate marker" for the efficacy of antiviral treatment. Now, however, viral load has been shown to be more reliable in monitoring treatment and also has been associated with progression of HIV disease: in general, the higher the viral load, the more rapid the progression of illness. In short, while CD4+ cell count can help with a diagnosis of how the patient is currently doing, CD4+ cell count and viral load together can help form a better prognosis of likely future outcomes.

Viral load tests are used to monitor the success of treatment and to suggest when a particular combination therapy is not working. Successful treatment often leads to a viral load reading "below the level of detection" (formerly, and somewhat confusingly, known as "undetectable"), indicating that the concentration of HIV in the blood is too low to be detected using a particular assay. Depending upon the assay, this may range from less than 500 to less than 40 copies of viral RNA per milliliter of plasma. While a viral load below the level of detection is an affirmation of good health, it emphatically does not mean that the blood is virus free or that viral load will remain low over time. Further, studies have shown that people who have viral loads below the level of detection in the blood may have virus in the semen or vaginal secretions which means that they remain potentially infectious.

When HIV develops resistance to a particular drug or combination the virus is said to "breakthrough" and viral load begins to rise. At this point, the provider usually recommends a new set of antiviral drugs. Choosing the new combination is a complex matter since issues of cross-resistance must be taken into account. Thus, while switching is possible, the number of times a change in regimen can be made is limited, and the potential of exhausting these limited options makes many people reluctant to change medications.

The Post-Vancouver State of Combination Treatment

Overall, for people living with HIV disease, as well as professionals working with them, the news about the effectiveness of combination therapies that emerged in 1996, particularly from that year's International AIDS conference in Vancouver, was heartening but also confusing. During and after the conference, mainstream media reporting made it seem as if a total cure had been discovered.

Following the conference, a spate of news coverage suggested an end to the epidemic. An article by Andrew Sullivan in the The New York Times Magazine was called "When Plagues End: Notes on the Twilight of an Epidemic," an overly optimistic title that reflected the tensions surrounding advances in treatment. There finally seemed to be a reason to hope that HIV disease might become a chronic and manageable illness for more than a small minority of those infected. Yet to proclaim that we were entering the "twilight of the epidemic" gave false hope, is and was misleading (especially for people without any access to treatment). While combination therapy does not eliminate HIV from the body, the virus only slowly develops resistance to the drugs in people who follow the strict schedule of medicine. This means that people who benefit from combination therapy cannot safely discontinue their strict schedule of medications without experiencing a rebound in viral activity. (There is research currently underway, however, into the use of "strategic treatment interruptions," that would allow people to miss doses.)

Two studies published in the journal Science, showed that although the virus lurked in the immune system of patients on triple combination therapy, it occupied very few cells, and even after two years of therapy had not developed resistance to the drugs. Dr. David Ho of the Aaron Diamond Center in New York said: "This news should be a motivation for patients to carry on and adhere closely to their regimen." These articles also reported that while HIV obtained from these people may not have been resistant after several years of treatment, the virus was still competent, that is, capable of causing widespread infection in the absence of effective drug therapy. These findings support the idea that treatment appears to need to be lifelong.

Steven Deeks, of the University of California, San Francisco, characterized drug failure as occurring most often in patients who have become drug resistant as a result of previous treatment or who have not adhered to dosage schedules. Deeks went on to explain that these studies "support the observation that in patients who have not taken antiviral drugs before and who take the combination as directed, 80 percent to 90 percent do well."

By early 1999, the overall euphoria -- as well as sensationalism and excessive optimism -- that followed the Vancouver conference had greatly diminished. "For many people, protease inhibitors are now 'old news'," said Alan Berkman, an HIV clinician in New York City, of the attitude among many patients by the end of 1998. "At first, there were all these dramatic examples of people rising from their deathbeds, but that was already a while ago. In the intervening time, people have seen that these medications are not a 'miracle cure,' and that they can be difficult to take. A lot of the skepticism about the medical system has returned among many patients, although there is still a recognition that antiretrovirals can help people with HIV stay well longer."

The mood identified by Berkman was reflected in the first post-Vancouver International AIDS Conference held in Geneva, Switzerland in July 1998. Where Vancouver displayed the revolutionary potential of the new treatment paradigm, the Geneva conference focused on small, incremental steps and careful analysis of existing data on combination therapies. Geneva covered a number of major themes, including the viral activity and mechanics of viral eradication, strengthening and rebuilding the immune system, drug resistance, new treatments, simpler drug regimens, strategies for using and adhering to antiviral drugs, longer-term side effects, and perinatal transmission. In almost every field, there was evidence that combination therapy continues to be effective over time, but that the drugs do not work for everyone, nor could anyone say how long the beneficial effect of treatment could be expected. Further a good deal of attention was paid to the problems of medication side effects and the challenge of adherence to demanding antiviral regimens.

The history of HIV treatments is a constantly unfolding one. Even as current therapies have demonstrated both enormous power and distinct limitations, new generations of treatments are in development.

Psychotherapist Michael Shernoff, M.S.W., and Body Positive Editor Raymond A. Smith, Ph.D. are co-authors of HIV Treatment: Mental Health Aspects of Antiviral Therapy (AIDS Health Project, University of California, San Francisco, 2000) from which this article was adapted.


Kaposi's Sarcoma and Pneumocystis Pneumonia Among Homosexual Men -- New York and California. MMWR 30(25): 305-307, July 3, 1981.

Horn, T. (1998). "Drug Resistance." In the Encyclopedia of AIDS: A Social, Political, Cultural, and Scientific Record of the HIV Epidemic. Ed., Raymond A. Smith. Chicago: Fitzroy Dearborn Publishers, 186.

Manos, T. Negron and Horn. (1998) "Antiviral Drugs." In the Encyclopedia of AIDS: A Social, Political, Cultural, and Scientific Record of the HIV Epidemic. Ed., Raymond A. Smith. Chicago: Fitzroy Dearborn Publishers, 70-72.

Centers for Disease Control and Prevention. (February 28, 1997). 1996 HIV/AIDS trends provide evidence of success in HIV prevention and treatment: AIDS deaths decline for the first time. CDC Press Summary.

Keen, L. (1998, February 6). AIDS: Survival rate continues to climb. New York Blade, V.2, No.6, p.3.

Sullivan, A. (1996, November, 10). When plagues end: Notes on the twilight of an epidemic. The New York Times Magazine, 52-84.

Wong, J.K., Hezarth, M., Gunthard, H.F., Havlir, D.V., Ignacio, C.C., Spina, C.A., Richman, D.D. (1997, November, 14). Viremia. Science, 278(5341):1291 (in Reports).

Finzi, D., Hermankova, M., Pierson, T., Carruth, L.M., Buck, C., Chaisson, R.E., Quinn, T.C., Chadwick, K., Margolick, J., Brookmeyer, R., Gallant, J., Markowitz, M., Ho, D., Richman, D.D., Siciliano, R.F. (1997, November 14). Identification of a Reservoir for HIV-1 in Patients on Highly Active Anti-Retroviral Therapy. Science, 278(5341): 1295 (in Reports).

Grady, D. (1997). AIDS virus hides out but doesn't turn resistant. The New York Times, November 14.

Risk factors

Behaviours and conditions that put individuals at greater risk of contracting HIV include:

  • having unprotected anal or vaginal sex
  • having another sexually transmitted infection (STI) such as syphilis, herpes, chlamydia, gonorrhoea and bacterial vaginosis
  • sharing contaminated needles, syringes and other injecting equipment and drug solutions when injecting drugs
  • receiving unsafe injections, blood transfusions and tissue transplantation, and medical procedures that involve unsterile cutting or piercing and
  • experiencing accidental needle stick injuries, including among health workers

AIDS, Spanish Flu, the PLAGUE? Just how deadly is the coronavirus compared to history’s WORST pandemics?

In a highly interconnected and globalized world, humanity is increasingly susceptible to outbreaks of disease. Recent decades have seen a slew of infectious illnesses spiral into epidemics and leave a trail of destruction in their wake.

Swine flu has claimed over half a million lives since it crossed over to humans in 2009 The West Africa ebola outbreak killed more than 11,000 people, and SARS, Bird flu and Mad Cow Disease also racked up hundreds of deaths and proved to be major causes for concern around the world.

Now people are gripped by fears of the deadly Coronavirus, which has infected over 17,000 and killed over 360 people in China alone. The virus has also spread to at least 20 other countries. While the situation is dire, it is important to put it in context.

Here, examines some of the deadliest pandemics in human history.

HIV/AIDS (25 million killed) 1981-2012

HIV/AIDS was first identified in the Democratic Republic of the Congo all the way back in 1976. The outbreak began in earnest in the early 80s, and it has remained one of the biggest scourges humanity has faced in recent decades. Nearly 25 million of the 65 million people infected during the pandemic died by the early 2000s, with 2.8 million people dying of AIDS in 2005 alone.

Both prevention and treatment for HIV infection have both vastly improved in the intervening years. According to the UN, some 37.9 million people were living with HIV by the end of 2018, of which 24.5 million were accessing antiretroviral therapy.

Asian Flu (2 million killed) 1956 - 1958

The Asian Flu virus originated in China in early 1956 before eventually spreading to Singapore, Hong Kong and the US. Though there are varying statistics for the exact death toll, World Health Organization data indicates that it claimed the lives of some two million people during its two-year rampage. Nearly 70,000 of the victims were in the US alone.

Research suggests the virus is a mixed species strain made up of avian flu and human flu viruses. Some scientists say the disease originated from a mutation in wild ducks that combined with a pre-existing human strain.

Spanish Flu (20 - 50 million killed) 1918

Arguably one of the worst pandemics to ever hit humanity, the Spanish Flu outbreak of 1918 spread from Asia, to Europe and North America, and even reached the Arctic and several remote Pacific islands.

Over 500,000,000 people were infected and between 20-50,000,000 people died before the pandemic ended in December 1920. Some researchers have estimated that the disease actually claimed 100,000,000 lives, which was roughly three to five percent of the Earth's population at the time.

What separated the flu from other influenza outbreaks was its unusual mortality pattern, which saw it strike down completely healthy young adults.

Black Death (75 - 200 million killed) 1346 - 1353

Perhaps the best known pandemic to ever hit humanity, the Black Death, racked up an obscenely high death toll of between 75 and 200 million people.

The plague completely devastated Europe, Africa and Asia, jumping continents via fleas living on rats that often travelled on merchant ships. In the seven years the Black Death lasted it killed between 30 and 60 percent of Europe's population.

Plague of Justinian (25 million killed) 541 - 542

A lesser-known pandemic, the plague of Justinian, afflicted the Byzantine Empire and is estimated to have cut Europe's population in half in just 12 months. Roughly 40 percent of Constantinople's population were killed and, at its height, the pandemic is believed to have killed an estimated 5,000 people per day.

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7 Worst Killer Plagues in history

Smallpox (also known by the Latin names Variola or Variola vera) is a contagious disease unique to humans. Smallpox is caused by either of two virus variants named Variola major and Variola minor. The deadlier form, V. major, has a mortality rate of 30–35%, while V. minor causes a milder form of disease called alastrim and kills

1% of its victims. Long-term side-effects for survivors include the characteristic skin scars. Occasional side effects include blindness due to corneal ulcerations and infertility in male survivors.

Smallpox killed an estimated 60 million Europeans, including five reigning European monarchs, in the 18th century alone. Up to 30% of those infected, including 80% of the children under 5 years of age, died from the disease, and one third of the survivors became blind.

As for the Americas, after the first contacts with Europeans and Africans, some believe that the death of 90 to 95 percent of the native population of the New World was caused by Old World diseases. It is suspected that smallpox was the chief culprit and responsible for killing nearly all of the native inhabitants of the Americas. In Mexico, when the Aztecs rose up in rebellion against Cortés, outnumbered, the Spanish were forced to flee. In the fighting, a Spanish soldier carrying smallpox died. After the battle, the Aztecs contracted the virus from the invaders’ bodies. When Cortes returned to the capital, smallpox had devastated the Aztec population. It killed most of the Aztec army, the emperor, and 25% of the overall population. Cortés then easily defeated the Aztecs and entered Tenochtitlán, where he found that smallpox had killed more Aztecs than had the cannons.

Smallpox was responsible for an estimated 300–500 million deaths in the 20th century. As recently as 1967, the World Health Organization (WHO) estimated that 15 million people contracted the disease and that two million died in that year. After successful vaccination campaigns throughout the 19th and 20th centuries, the WHO certified the eradication of smallpox in 1979. To this day, smallpox is the only human infectious disease to have been completely eradicated from nature.

2 Spanish Flu (1918 – 1919):Killed 50 to 100 million people worldwide in less than 2 years

In 1918 and 1919, the Spanish Flu pandemic killed more people than Hitler, nuclear weapons and all the terrorists of history combined. (A pandemic is an epidemic that breaks out on a global scale.) Spanish influenza was a more severe version of your typical flu, with the usual sore throat, headaches and fever. However, in many patients, the disease quickly progressed to something much worse than the sniffles. Extreme chills and fatigue were often accompanied by fluid in the lungs. One doctor treating the infected described a grim scene: “The faces wear a bluish cast a cough brings up the blood-stained sputum. In the morning, the dead bodies are stacked about the morgue like cordwood.”

If the flu passed the stage of being a minor inconvenience, the patient was usually doomed. There is no cure for the influenza virus, even today. All doctors could do was try to make the patients comfortable, which was a good trick since their lungs filled with fluid and they were wracked with unbearable coughing. The “bluish cast” of victims’ faces eventually turned brown or purple and their feet turned black. The lucky ones simply drowned in their own lungs. The unlucky ones developed bacterial pneumonia as an agonizing secondary infection. Since antibiotics hadn’t been invented yet, this too was essentially untreatable. The pandemic came and went like a flash. Between the speed of the outbreak and military censorship of the news during World War I, hardly anyone in the United States knew that a quarter of the nation’s population — and a billion people worldwide — had been infected with the deadly disease. More than half a million died in the U.S. alone worldwide, more than 50 million.

3 Black Death (1340 – 1771):Killed 75 million people worldwide

The Black Death, or The Black Plague, was one of the most deadly pandemics in human history. It began in South-western or Central Asia and spread to Europe by the late 1340s. The total number of deaths worldwide from the pandemic is estimated at 75 million people there were an estimated 20 million deaths in Europe alone. The Black Death is estimated to have killed between a third and two-thirds of Europe’s population.

The three forms of plague brought an array of signs and symptoms to those infected. Bubonic plague refers to the painful lymph node swellings called buboes, mostly found around the base of the neck, and in the armpits and groin. The septicaemic plague is a form of blood poisoning, and pneumonic plague is an airborne plague that attacks the lungs before the rest of the body. The classic sign of bubonic plague was the appearance of buboes in the groin, the neck and armpits, which oozed pus and bled. Victims underwent damage to the skin and underlying tissue, until they were covered in dark blotches. Most victims died within four to seven days after infection. When the plague reached Europe, it first struck port cities and then followed the trade routes, both by sea and land. The bubonic plague was the most commonly seen form during the Black Death, with a mortality rate of thirty to seventy-five percent and symptoms including fever of 38 – 41 °C (101-105 °F), headaches, painful aching joints, nausea and vomiting, and a general feeling of malaise. Of those who contracted the bubonic plague, 4 out of 5 died within eight days. Pneumonic plague was the second most commonly seen form during the Black Death, with a mortality rate of ninety to ninety-five percent.

The same disease is thought to have returned to Europe every generation with varying virulence and mortalities until the 1700s. During this period, more than 100 plague epidemics swept across Europe. On its return in 1603, the plague killed 38,000 Londoners. Other notable 17th century outbreaks were the Italian Plague of 1629-1631, the Great Plague of Seville (1647-1652), the Great Plague of London (1665–1666), the Great Plague of Vienna (1679). There is some controversy over the identity of the disease, but in its virulent form, after the Great Plague of Marseille in 1720–1722 and the 1771 plague in Moscow it seems to have disappeared from Europe in the 18th century. The fourteenth-century eruption of the Black Death had a drastic effect on Europe’s population, irrevocably changing Europe’s social structure. It was a serious blow to the Roman Catholic Church and resulted in widespread persecution of minorities such as Jews, foreigners, beggars and lepers. The uncertainty of daily survival created a general mood of morbidity influencing people to “live for the moment”, as illustrated by Giovanni Boccaccio in The Decameron (1353).

4 Malaria (1600 – today):Kills about 2 million people per year

Malaria causes about 400–900 million cases of fever and approximately one to three million deaths annually — this represents at least one death every 30 seconds. The vast majority of cases occur in children under the age of 5 years pregnant women are also especially vulnerable. Despite efforts to reduce transmission and increase treatment, there has been little change in which areas are at risk of this disease since 1992. Indeed, if the prevalence of malaria stays on its present upwards course, the death rate could double in the next twenty years. Precise statistics are unknown because many cases occur in rural areas where people do not have access to hospitals or the means to afford health care. Consequently, the majority of cases are undocumented.

Malaria is one of the most common infectious diseases and an enormous public-health problem. It’s parasites are transmitted by female Anopheles mosquitoes. The parasites multiply within red blood cells, causing symptoms that include symptoms of anemia (light headedness, shortness of breath, tachycardia etc.), as well as other general symptoms such as fever, chills, nausea, flu-like illness, and in severe cases, coma and death. The disease is caused by protozoan parasites of the genus Plasmodium. It is widespread in tropical and subtropical regions, including parts of the Americas, Asia, and Africa.

5 AIDS (1981 – today):Killed 25 million people worldwide

Acquired Immune Deficiency Syndrome (AIDS) has led to the deaths of more than 25 million people since it was first recognized in 1981, making it one of the most destructive epidemics in recorded history. Despite recent improved access to antiretroviral treatment and care in many regions of the world, the AIDS epidemic claimed approximately 3.1 million (between 2.8 and 3.6 million) lives in 2005 (an average of 8,500 per day), of which 570,000 were children. UNAIDS and the WHO estimate that the total number of people living with the human immunodeficiency virus (HIV) has reached its highest level. There are an estimated 40.3 million (estimated range between 36.7 and 45.3 million) people now living with HIV. Moreover, almost 5 million people have been estimated to have been infected with HIV in 2005 alone.

The pandemic is not homogeneous within regions with some countries more afflicted than others. Even at the country level there are wide variations in infection levels between different areas. The number of people living with HIV continues to rise in most parts of the world, despite strenuous prevention strategies. Sub-Saharan Africa remains by far the worst-affected region, with 23.8 million to 28.9 million people living with HIV at the end of 2005, 1 million more than in 2003. Sixty-four percent of all people living with HIV are in sub-Saharan Africa, as are more than 77% of all women living with HIV. South & South East Asia are second most affected with 15%.

The key facts surrounding this origin of AIDS are currently unknown, particularly where and when the pandemic began, though it is said that it originated from the apes in Africa.

6 Cholera (1817 – today):8 pandemics hundreds of thousands killed worldwide

In the 19th century, Cholera became the world’s first truly global disease in a series of epidemics that proved to be a watershed for the history of plumbing. Festering along the Ganges River in India for centuries, the disease broke out in Calcutta in 1817 with grand – scale results. When the festival was over, they carried cholera back to their homes in other parts of India. There is no reliable evidence of how many Indians perished during that epidemic, but the British army counted 10,000 fatalities among its imperial troops. Based on those numbers,, it’s almost certain that at least hundreds of thousands of natives must have fallen victim across that vast land. Cholera sailed from port to port, the germ making headway in contaminated kegs of water or in the excrement of infected victims, and transmitted by travelers. The world was getting smaller thanks to steam-powered trains and ships, but living conditions were slow to improve. By 1827 cholera had become the most feared disease of the century.

The major cholera pandemics are generally listed as: First: 1817-1823, Second: 1829-1851, Third: 1852-1859, Fourth: 1863-1879, Fifth: 1881-1896, Sixth: 1899-1923: Seventh: 1961- 1970, and some would argue that we are in the Eighth: 1991 to the present. Each pandemic, save the last, was accompanied by many thousands of deaths. As recently as 1947, 20,500 of 30,000 people infected in Egypt died. Despite modern medicine, cholera remains an efficient killer.

7 Typhus (430 BC? – today):Killed 3 million people between 1918 and 1922 alone, and most of Napoleon’s soldiers on Russia

Typhus is any one of several similar diseases caused by louse-borne bacteria. The name comes from the Greek typhos, meaning smoky or lazy, describing the state of mind of those affected with typhus. Rickettsia is endemic in rodent hosts, including mice and rats, and spreads to humans through mites, fleas and body lice. The arthropod vector flourishes under conditions of poor hygiene, such as those found in prisons or refugee camps, amongst the homeless, or until the middle of the 20th century, in armies in the field.

The first description of typhus was probably given in 1083 at a convent near Salerno, Italy. Before a vaccine was developed in World War II, typhus was a devastating disease for humans and has been responsible for a number of epidemics throughout history. During the second year of the Peloponnesian War (430 BC), the city-state of Athens in ancient Greece was hit by a devastating epidemic, known as the Plague of Athens, which killed, among others, Pericles and his two elder sons. The plague returned twice more, in 429 BC and in the winter of 427/6 BC. Epidemic typhus is one of the strongest candidates for the cause of this disease outbreak, supported by both medical and scholarly opinions. Epidemics occurred throughout Europe from the 16th to the 19th centuries, and occurred during the English Civil War, the Thirty Years’ War and the Napoleonic Wars. During Napoleon’s retreat from Moscow in 1812, more French soldiers died of typhus than were killed by the Russians. A major epidemic occurred in Ireland between 1816-19, and again in the late 1830s, and yet another major typhus epidemic occurred during the Great Irish Famine between 1846 and 1849.

In America, a typhus epidemic killed the son of Franklin Pierce in Concord, New Hampshire in 1843 and struck in Philadelphia in 1837. Several epidemics occurred in Baltimore, Memphis and Washington DC between 1865 and 1873. During World War I typhus caused three million deaths in Russia and more in Poland and Romania. De-lousing stations were established for troops on the Western front but the disease ravaged the armies of the Eastern front, with over 150,000 dying in Serbia alone. Fatalities were generally between 10 to 40 percent of those infected, and the disease was a major cause of death for those nursing the sick. Following the development of a vaccine during World War II epidemics occur only in Eastern Europe, the Middle East and parts of Africa.

How To Demand A Medical Breakthrough: Lessons From The AIDS Fight

AIDS activist group ACT UP organized numerous protests on Wall Street in the 1980s. The group's tactics helped speed the process of finding an effective treatment for AIDS.

In the summer of 1985, Mike Petrelis was savoring life as young, openly gay man in New York City. He'd landed a cool job working for a film publicist who mostly handled foreign art films. He'd found an affordable apartment — not far from the gay mecca of Greenwich Village.

Then one day, Petrelis noticed a sort of blotch on his arm.

He went to a doctor, who ran a new kind of test, and gave Petrelis the verdict: "You have AIDS."

"He was saying that if I was going to be lucky I'd have six months to maybe two years of life left," recalls Petrelis.

Petrelis says he broke down crying. The doctor said he'd give Petrelis a moment to be alone, pull himself together.

And sitting in that pristine exam room, Petrelis made his first act of protest: "I took out a cigarette."

This story is part of a series from NPR's Science desk called "The Other Side of Anger." There's no question we are in angry times. It's in our politics, our schools and homes. Anger can be a destructive emotion but it can also be a positive force.

Join NPR in our exploration of anger and what we can learn from this powerful emotion. Read and listen to stories in the series here.

He did it precisely because he knew it was forbidden.

"I was so mad with hearing this news — so angry at the doctor — I thought the one best way to protest would be to light up a cigarette and just smoke it with as much pleasure as I could find," he says.

But in the months that followed Petrelis soon shifted the focus of his rage, as he began to learn just how little the government and medical establishment had done to address a crisis that, at the time, mostly afflicted gay men. This was four years after AIDS first made headlines. More than 6,000 Americans had already died. Yet the budget for AIDS research was a fraction of what the U.S. government spent on diseases that were far less threatening. President Ronald Reagan had yet to even say the word AIDS in public. And only one private pharmaceutical company was seriously pursuing a treatment.

"I mean, my anger just knew no limits," says Petrelis.

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Over the next decade, this rage would drive not just Petrelis but thousands of gay men and their supporters to form one of the most influential patient advocacy groups in history.

They called themselves AIDS Coalition to Unleash Power — or ACT UP. And they ultimately forced the government and the scientific community to fundamentally change the way medical research is conducted — paving the way for the discovery of a treatment that today keeps alive an estimated half-million HIV-positive Americans and millions more worldwide.

But as central as anger was to ACT UP's success, it would also prove a force for division.

"It was a war zone"

All this was unimaginable to Petrelis back in 1985. As furious as he was with the government, he was just as indignant that so few other gay men around him seemed to echo his rage.

"I just thought because I was so angry that there should have been more angry people," he recalls.

The gay and lesbian community had created a dynamic network of self-help groups in response to the crisis. But their focus was on providing comfort to the sick: buddies to take you to hospital, lawyers to help you write your will.

Petrelis remembers exploding at one of them: "I don't want to write my will! I want a cure!"

One of the recruits to those self-help groups was a young lawyer named David Barr. Back then he felt too overwhelmed to give much thought to asserting his anger.

All around him fellow gay men were suddenly falling sick with horrific symptoms — skin cancer, extreme weight loss, incontinence. Hospitals were turning them away. Employers were denying them benefits.

"It was a war zone," Barr recalls. So at first his overriding feeling was, "I don't have time to go yell at politicians. I've got to diaper somebody. I've got to create a legal services program to keep people from being evicted."

But Barr was also starting to grow restless. The work he was doing to set up support systems felt vital.

"But it was never satisfying," he says. "Because whatever help we were providing was really temporary. We lost everybody."

Boiling over

By early 1987, with the U.S. death toll topping 40,000 and worldwide HIV infections reaching 5 to 10 million, the threat was starting to feel apocalyptic. The gay community's mounting frustration finally boiled over in an explosive show of anger.

Hundreds of gay men and their supporters took to New York City's streets to vent their fury — first with a demonstration on Wall Street. Then a protest at city hall. Then an even bigger showdown on Wall Street.

Barr and Petrelis had been to gay rights demonstrations before — pride rallies, candlelight vigils for people who had died of AIDS. But this time, says Petrelis, "something felt different."

People weren't just chanting or carrying signs. They were blocking traffic with their bodies.

At the second Wall Street action, "over a hundred people got arrested," Barr says. Many of them were people who had never contemplated civil disobedience before.

"It was such a terrific feeling to be arrested with my yoga teacher," Petrelis recalls with a chuckle.

And it was profoundly affirming. "All those men and women screaming at the top of their lungs — I felt they were taking my anger and putting it out there to the world."

For Barr, participating in the outpouring was galvanizing.

"Rallying together and expressing our anger was a really good replacement for just feeling scared all the time," he says.

"It felt powerful. And it gave us a way of saying, 'OK, we've got to do something more than just buy people groceries, and take them to the hospital, and plan memorial services.' The anger is what helped us fight of a sense of hopelessness."

Soon the group — which the New York demonstrators named ACT UP at an early planning meeting — was going national, with thousands of people across the country staging similar actions.

Getting strategic

ACT UP quickly made its name with tactics that were unapologetically confrontational, says David France, the author of a history of AIDS activism called How to Survive a Plague, as well as a 2012 documentary by the same name.

"ACT UP's ethos was that they had united in anger," he says.

"They would storm people's offices with fake blood and cover people's computers with [it]," he says. "They locked themselves to politicians' desks. At one point, they barged into a meeting of a pharmaceutical company and turned over the shrimp cocktail tables."

Demonstrators from the organization ACT UP protest in front of the headquarters of the Food and Drug Administration. The FDA opened up access to experimental drugs soon after. J. Scott Applewhite/AP hide caption

This made them extremely intimidating. "They were no longer invisible sufferers of a disease. They were terrifying sufferers of a disease," says France.

But initially, says France, "the actions had the air of purposeless anger."

That changed when ACT UP began to deploy its anger strategically.

Barr says the demonstrations started off as a simple release: "We were angry and we needed to express ourselves."

But in doing so, he says, "we began to realize, 'Oh, this is a tactic that we can put to good use.' "

So they took it upon themselves to figure out the specific roadblocks in government policy and clinical trials that stood in the way of what ACT UP wanted most: a cure. Then they unleashed their rage to force the decision-makers to hear ACT UP's solutions.

They kicked off the approach at a government building in suburban Maryland.

"Our goal was to seize control of the FDA," says Barr.

ACT UP wanted the Food and Drug Administration to give AIDS patients access to an experimental drug. The FDA wouldn't even discuss it.

So hundreds of activists converged on the FDA's headquarters.

"One group were wearing lab coats that were stained with bloody hands," recalls Barr. "Other people brought tombstones that they made and lied down in front of the building and held up the tombstones: 'Dead from FDA red tape.' "

The activists advanced in rows, blocking the entrances. The demonstration made national news.

Within days the FDA agreed to meet. In a couple months, officials opened up the policy on access to experimental drugs.

France says the two prongs of ACT UP's strategy were equally important. The aggressive protests got them a foot in the door, but it wouldn't have made a difference if they hadn't done the homework needed to offer insightful and viable proposals once they did get a meeting.

"What made this work was not just the anger. But the anger coupled with the intelligence," says France.

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ACT UP came to call this approach its "inside-outside strategy." And they deployed it over and over again — with the National Institutes of Health, and then with pharmaceutical companies, eventually becoming full partners with key scientists.

The upshot of all this: "What they were able to revolutionize was really the very way that drugs are identified and tested," says France.

This included scrapping the prevailing practice of testing drugs on a small number of people over a long period of time in favor of testing a huge sample of people over a much shorter period — significantly speeding up the time it took to conduct drug trials.

December 1989: At left, members of ACT UP mount a protest outside St. Patrick's Cathedral in New York. At right, activist Michael Petrelis inside the cathedral shouts "Stop killing us!" in the middle of the service. Images from the documentary "How to Survive a Plague" by David France hide caption

Similarly, ACT UP insisted that the researchers and pharmaceutical companies that were searching for a cure for AIDS also research treatments for the opportunistic infections that were killing off AIDS patients while they waited for a cure.

In the process, says France, "ACT UP created a model for patient advocacy within the research system that never existed before."

Today it seems natural that people suffering from a disease — whether that's breast cancer or diabetes — should have a voice in how it is researched and treated. But France says this was decidedly not the norm before ACT UP.

In 1996, scientists finally did find the treatment that would keep people alive. France says while scientists would probably have made the discovery eventually, there's "no question" ACT UP made it happen sooner.

But an organization that uses anger as a tool also faces a challenge. Once you get people to tap into their rage — it's hard to control it.

"Stop killing us!"

That contradiction came to a head for ACT UP one Sunday in December of 1989 at Manhattan's St. Patrick's Cathedral.

Outside the church, ACT UP was staging a massive demonstration to call out Archbishop John O'Connor for opposing the use of condoms.

Petrelis was part of a smaller group that decided to take the protest inside — to the mass.

He'd been raised Roman Catholic and had a lot of unresolved feelings toward the church.

"You know condemning me as gay, just all that Catholic guilt I had been raised with," he says.

They didn't want to disrespect parishioners, so the plan was to wait for O'Connor to begin his sermon, interrupt by reading a quick statement, then turn their backs on him in silent protest.

But as Petrelis watched his fellow activists begin, he says something inside of him stirred: "I felt there was just not enough anger that could be heard."

Petrelis had a whistle with him — the kind for calling for help when you're being attacked. He started blowing it.

"Loudly," he recalls, "I stood up on the pew literally blowing the whistle on centuries of horrible treatment by the church toward gays and towards women."

Even that didn't feel like enough. Petrelis pointed his finger at the archbishop: "I started screaming, 'Stop killing us! Archbishop O'Connor, Stop killing us!' "

France's documentary includes footage of the moment — Petrelis standing on the pew, other activists taking up the chant "Stop it! Stop it!" Still more leaping into the aisle and laying on the floor as police march in to cart them off.

O'Connor continued the service. An activist lined up for communion, then took the wafer the priest had given him, and crumpled it.

The aftermath

David Barr had opposed this protest. The result confirmed his fears.

"The next day the story on the front pages of the newspapers was not, 'Look at all these horrible HIV policies the church is promoting.' It was, 'Gay guy spits body of Christ out on the floor.' "

Barr was part of a contingent within ACT UP that felt the time had come for a new phase. He believed ACT UP's inside-outside strategy had largely succeeded. Top policy makers and scientists were now giving ACT UP's proposals a respectful hearing.

But AIDS activists had not yet convinced the political class to mobilize the full resources of the federal government behind the search for a cure. For that, ACT UP would need to build this into a movement of not thousands but hundreds of thousands — the kind that sways elections. And this would require reaching out to all sorts of other groups affected by AIDS, such as Latinos — who are Catholic.

"I just remember my first thought being, well that's the end of our coalition building with the Latino community," Barr says. "That's it. Nobody's going to talk to us."

ACT UP continued to mount demonstrations — there are active chapters of the organization to this day. But to Barr it marked the beginning of the end of ACT UP's effectiveness.

"It was a turning point where venting one's anger took precedent over political strategy," he says.

Within a year Barr and many others who had been central to the organization's meetings with top researchers had parted ways — splitting off into groups with a more traditional style of lobbying and politicking.

As for Petrelis, he has no regrets.

In general, he disputes the notion that ACT UP became less strategic and effective from that point on. And while he concedes, what happened at St. Patrick's Cathedral was unplanned and not in service of any tactical objective, he argues in the broader scheme it was deeply necessary.

"It was a catharsis finally happening," he says.

And not just for the activists in the cathedral, he says. Petrelis has been in movie theaters when David France's documentary has been shown.

When that scene comes on — of his younger self screaming at the archbishop — "people stand up," he says, "and they applaud me."