HIV and AIDS: The Never-Ending Story
At first, it seemed like an American disease. In June 1981, the Centers for Disease Control and Prevention (CDC) in Atlanta reported in their Morbidity and Mortality Weekly Report (MMWR) that between October 1980 and May 1981, five young men in Los Angeles, all active homosexuals, were treated for biopsy-confirmed Pneumocystis carinii pneumonia (PCP). Three of these patients had evidence of depressed immune function and two died. MMWR is a weekly summary for the United States of important, time-sensitive public health information. In the comments accompanying this small case series, the editors noted that historically, Pneumocystis - a yeast-like fungus - infects only patients with severely compromised immune systems, so its occurrence in these previously healthy individuals raised the possibility of immune dysfunction secondary to some predisposing common exposure. That all of the patients were homosexuals suggested an association with some aspect of homosexual lifestyle or a disease acquired through homosexual contact.1
From this first report, the CDC became the coordinator for emerging information on this new disease and MMWR the major information source as the knowledge base grew and evolved. Only 4 weeks after that first release, MMWR reported that over the last two and a half years, Kaposi’s sarcoma (KS) had been diagnosed in 26 young homosexual men, 20 in New York City and six in California. Until that time, KS was known as a rare skin cancer that presented as circumscribed dark purple lesions and that only occurred in elderly men of Mediterranean descent - characteristics not shared by any of these young men. Notably, six of these KS patients had also developed Pneumocystis pneumonia. In contrast to the usual KS course where mean survival time was 8-13 years, eight patients died within 2 years of diagnosis.2 By September, there was a second series of eight patients with atypical KS. Again, all were young homosexual men and survival time was short: half of the patients were dead within 20 months of diagnosis.The authors reported the historic association of KS with an immune-compromised state in a subset of cases in Africa, but no immune testing was performed in either of these two groups.2
The epidemiology of this new disease unrolled rapidly with critical new reports almost every month. By the end of 1981 - only six months after the first report - outbreaks of bizarre opportunistic infections and of unusual malignancies in young homosexuals had been reported from major cities all over the United States. By this time, these disparate cases were found to be linked by definite evidence of immune dysfunction focused on the cellular immune response of lymphocytes, the white blood cells that determine the body’s response to infectious microorganisms and other foreign substances. The characteristic pattern was moderate to severe lymphopenia (low lymphocyte counts); specifically, low counts of helper/inducerT4+ lymphocytes - now called CD4 cells - and correspondingly, a low T4+ to T8+ lymphocyte ratio (T8+ lymphocytes are suppressor/cytotoxic lymphocytes, now called CDS cells); and anergy (no lymphocyte response to antigen stimulation).
Then in December 1981, opportunistic infections associated with cellular immune dysfunction were reported for the first time in heterosexual men and women who were intravenous drug users (IDUs). 'The combined evidence indicated a new disease caused by a transmissible agent that attacked the immune system in specific, vulnerable populations. Most concerning was the exponential increase in cases and the expanding base of susceptible populations - by the end of 1981 in the United States, there were 270 reported cases of this severe, new, acquired immune deficiency among gay men and 121 of these individuals had already died.3
Media coverage played a critical role in the evolution of the AIDS story. In the beginning, coverage of the new disease outbreak was very limited. Reports described a “new and mysterious illness”in gay men with little additional information. Quantitative content analysis of press coverage of HIV/AIDS in Australia, US, France, and Britain during the 1980s and 1990s revealed a common pattern with coverage focused almost exclusively on homosexuals.6
It is not a coincidence that AIDS emerged in the early 1980s when after centuries of persecution, the gay liberation movement was in full swing in the United States. For a minority of young homosexual men, liberation meant an extravagantly active sex life with multiple sexual partners in places like public bathhouses. In spite of gay pride parades and stories of “coming out,” the longstanding stigma of homosexuality persisted with overt homophobia through the 1980s, even in New York City and San Francisco, both sophisticated metropolitan centers with flourishing gay subcultures - and both among the first cities to report cases of the new illness. From the beginning, news coverage of the disease was dominated by the initial CDC reports of “gay pneumonia,” alluded to in 83 % of stories in 1981.6 The labels “gay plague ” and Gay-Related Immune Disease (GRID) first appeared in 1981, establishing the public view of the illness as exclusively a contagious disease of homosexuals.7
On July 3, 1981, the same day this information was published in MMWR, the New York Times reported “Rare Cancer Seen in 41 Homosexuals," describing the outbreak of Kaposi’s sarcoma, “a rare and often rapidly fatal form of cancer,” diagnosed in homosexual men. The article- one of the first in a lay publication to address the new outbreak - explained that the diagnoses had been made mostly in New York City and San Francisco, and that the CDC was alerting other doctors who treat “large numbers of homosexual men” of the problem.* Beginning with the headline, the article clearly suggested that this cancer was a homosexual problem, just like the unusual infections and the immune system dysfunction.
Early in 1982, a small case series described immunologic findings in 15 healthy homosexual men and two men with KS. Both KS patients and seven of the 15 healthy gay volunteers had lowT4+/T8+ (helper/suppressor) lymphocyte ratios - the same pattern seen in individuals with opportunistic infections and KS. High cytomegalovirus (CMV) antibody titers - evidence of previous CMV infection - were found in 14 of the 15 men and half of the group reported exposure to inhaled nitrites. A history of CMV infection and of amyl nitrite use had been noted in prior reports of both opportunistic infections and KS, and the authors of this report suggested the combination might be the cause of the immune dysfunction. It would be many months before this immunologic pattern was instead recognized as a pre- clinical stage of the new infectious disease.4
Within months, a series of critical reports raised new concerns about spread of the epidemic. First, the CDC reported that between June 1981 and May 1982, a total of 355 cases of KS and/or serious opportunistic infection had occurred in previously healthy people between 15 and 60 years of age. Sixteen per cent of the group were heterosexual and of these, the majority had a history of IV drug use. Similarities between the homosexual and heterosexual cases in age range, fatality rates, and geographic and temporal distribution strongly suggested that the cases were all part of the same disease outbreak.10
A critical report from the CDC in May 1982 described cases of persistent, generalized lymphadenopathy (lymph node enlargement) in homosexual males, reported by physicians from several major cities. In a subset of these men seen at medical centers in Atlanta, New York City, and San Francisco, immunologic evaluation demonstrated immune dysfunction with abnormal T-lymphocyte helper-to-suppressor ratios, the same pattern described in individuals with overt opportunistic infections and KS. Approximately 70% of these patients also had some constitutional symptoms including fatigue, fever, night sweats, and weight loss. One patient in the group went on to develop KS before the study ended. A direct relationship between the immunologic findings for these patients with lymphadenopathy and patients with opportunistic infections and/or KS could not be demonstrated, but the possibility was raised that this lymphadenopathy was an early expression of infection with the same transmissible agent attacking homosexual men and IV drug users.11
Only a month later, the CDC reported the now familiar disease pattern of opportunistic infections (OIs) in 34 Haitians (33 males) living in the United States; most had immigrated within the last 2 years. Almost half the group had experienced multiple opportunistic infections. Age range was similar to other reported groups, but only a small minority were homosexuals or IV drug users. When immunologic studies were performed, there was severe T-cell dysfunction with a marked decrease of the T-helper cell subset and inversion of the normal ratio ofT-helper to T-suppressor cells. For the entire group, the mortality rate on follow-up was nearly
50%. The similarity of the disease pattern and immunologic picture in Haitians recently entering the United States to that described in American homosexual males and IV drug users suggested an as-yet unidentified common cause.12
And a week after that, the CDC reported three cases of opportunistic PCP in individuals with hemophilia but with no other underlying disease. All three were heterosexual males who had received repeated injections of factorVOI concentrate to stop uncontrolled bleeding. To treat clotting factor deficiencies like those found in hemophiliacs, pooled concentrates of the missing factor from hundreds of donors are needed. None of these three patients had a history of homosexual contact or intravenous drug abuse, but two patients who were specifically tested had evidence of cellular immune deficiency and all had lymphopenia. The CDC editors of the report wrote,
The clinical and immunologic features of these three patients are strikingly similar to those recently observed among ... homosexual males, heterosexuals who abuse IV drugs, and Haitians who recently entered the United States. Although the cause of the severe immune dysfunction is unknown, the occurrence among the three hemophiliac cases suggests the possible transmission of an agent through blood products.'1
By December 1982, the CDC reported that all three of the original hemophilia patients had died, and there were four more cases and one suspected case among hemophiliacs receiving frequent clotting factor transfusions; two were children under 10 years of age. All had the now familiar pattern of cellular immune dysfunction - profoundly depressed lymphocyte counts and reversed CD4:CD8 ratios. As noted in cases from all the other risk groups, antibodies to another viral infection - in this case, hepatitis В - were prevalent in the hemophilia patients.14 A national survey of hemophilia treatment centers revealed that 30% of all hemophiliacs had abnormal immunologic tests.13
With these cases, the evidence seemed clear that a dangerous new transmissible agent was attacking the immune system of healthy individuals in multiple different settings. At an urgent meeting convened in July 1982 to specifically address this risk in individuals with hemophilia, the CDC adopted the term “acquired immune deficiency syndrome” to describe the clinical and immunologic pattern in all these groups and the acronym AIDS was born.15
Another intriguing piece of the puzzle emerged in September with evaluation of immune function in 81 male homosexual volunteer research subjects in NYC: 50 were asymptomatic and 31 had one or more of the constellation of symptoms described in association with generalized lymphadenopathy. T-cell subsets were abnormal in both groups compared with those of a control group of healthy heterosexual males: T4/T8 ratio averaged 1.8 in the controls compared with 1.1 in the asymptomatic homosexuals and 0.8 in the symptomatic group.TheT4/T8 ratio decreased as the number of sexual partners increased. Although not explicitly stated by the researchers, these results suggested that a large proportion of sexually active homosexual males in NYC could already have been infected by the AIDS agent with significant but, to this time, asymptomatic immune dysfunction.16 The findings were a chilling premonition of what was to come.
In the September 24 edition of MMWR, the CDC provided the following case definition of AIDS which included recognition of a pre-symptomatic state:
AIDS is an opportunistic infection at least moderately predictive of a defect in cell-mediated immunity, occurring in a person with no known cause for diminished resistance to that disease. Such diseases include Kaposi’s Sarcoma, Pneumocystis carinii pneumonia, and other serious opportunistic infections.... this case definition may not include the full spectrum of AIDS manifestations, which may range from absence of symptoms despite laboratory evidence of immune deficiency to non-specific symptoms (e.g., fever, weight loss, generalized, persistent lymphadenopathy) to specific diseases that are insufficiently predictive of cellular immunodeficiency to be included in incidence monitoring (e.g., tuberculosis, oral candidiasis, herpes zoster) to malignant neoplasms that cause, as well as result from, immunodeficiency. Absence of a reliable ... test for AIDS makes th(is) working case definition the best currently available for incidence monitoring.17
By December 1982, the potential number of “at-risk” groups had increased even further, with the report of AIDS in a 20-month-old baby who had unexplained cellular immunodeficiency and repeated opportunistic infections after multiple blood and platelet transfusions for Rh incompatibility as a newborn. One of the platelet transfusions the baby received was ultimately found to have come from a homosexual man who was well when he donated blood but who died of AIDS-related opportunistic infection 17 months later.18-1''This case was a bombshell suggesting not only transmission of the infectious AIDS agent in blood transfusions but also a long incubation period for the infectious agent before symptoms appear.
Only a week later, a whole new risk group emerged when the CDC reported four cases of AIDS in babies less than 2 years of age. None had ever received blood or blood products, but three had mothers from groups at risk for AIDS and the mother of the last child had AIDS. In addition, the cases of six young children who died with opportunistic infections and unusual cellular immunodeficiencies were also under investigation, as were those of another 12 children with similar immunodeficiencies but without life-threatening opportunistic infections.20 Clinical features in these infants included growth failure, oral candidiasis (fungal infection), enlarged liver and spleen, generalized lymphadenopathy and chronic pneumonitis without a demonstrable infection. Seven of the nine mothers for whom information was available were intravenous drug users.
The pattern of immune dysfunction described in these infant AIDS cases closely resembled that seen in adults with AIDS. One mother had already died with AIDS and the others came from groups at risk for AIDS. Taken together, these cases suggested the infectious agent had been transmitted from mothers with AIDS or a pre-AIDS high-risk state to their children before birth or during delivery. As most of the mothers were well, the series supported the important, emerging concept of a long incubation period for the AIDS agent before symptoms appear.
By the end of 1982, the CDC reported a total of 788 AIDS cases, 95% from one of four identified risk groups - homosexual men, heterosexual IV drug users, Haitians, and hemophiliacs - the “4H club,” as it was called with predictable stigmatizing results.21 Although transfusion of blood products in general did not make the list of specified risk situations, the hemophiliac cases and the baby who developed AIDS after a platelet transfusion from a man who subsequently died of AIDS were considered important, confirmatory evidence that the AIDS agent was blood- borne and could be transmitted by transfusion of blood and blood products. Official meetings were initiated with the blood services community to address this issue. Transmission from mother-to-child was not considered a confirmed risk group at that time.
The disease pattern changed dramatically in the first week of 1983 with a resulting major shift in the scientific and public response when the CDC reported AIDS in two women who had developed cellular immunodeficiency with no other risk factors except long-term sexual relationships with partners who had AIDS. AIDS had been diagnosed in an additional 41 previously healthy women who were in no other identified risk category: four of these women had steady sexual partners who were IV drug users.22-23 It was suddenly and alarmingly clear that the unidentified AIDS agent could be transmitted by heterosexual sex.
And then there were the children. After the original report at the end of 1982, two more series reported AIDS cases in infants and young children.24,25 All were small at birth and had severe growth failure with lymphadenopathy, hepato-splenomegaly (enlarged liver and spleen) and recurrent infections with rare organisms, associated with profound cell-mediated immunodeficiency. In each case, at least one parent had AIDS or a recognized high-risk condition for AIDS. At the time of the report, 27% of the children had already died.
An additional risk factor was confirmed by a national case-control study which compared 50 male homosexuals with AIDS to 120 matched healthy male homosexual controls, all volunteer research subjects from clinics in New York City' San Francisco, Los Angeles, or Atlanta. The two groups were interviewed and their responses to a wide array of personal and socio-demographic questions were recorded. The most significant finding was a striking difference in the number of sexual partners: the AIDS patients had a median of 68 partners in the last 12 months compared with 35 for controls. The number of sex partners correlated significantly with many other high-risk variables including meeting partners in bathhouses, previous history of syphilis, and use of nitrite inhalants.26 Increased AIDS risk with multiple partners suggesting increased risk with increased exposure had emerged in other studies, but it had never been clarified as specifically as it was here.
Looking forward just 18 months from that first report in July 1981, that small case series sounded the alarm on a new epidemic caused by an unidentified agent that decimated the immune system.The pathogen that caused AIDS was carried in body fluids and was transmitted sexually and through the blood. Multiple high-risk groups had been defined: homosexual males (especially those with multiple partners); heterosexual IV drug users; women whose sex partners had or were at high risk for AIDS, i.e., bisexual males or IV drug users; hemophiliacs who had received multiple clotting factor infusions; infants born to mothers who had or were at high risk for AIDS; and recipients of infected blood transfusions. (Haitian immigrants were also identified as a high-risk group and resolution of this putative etiology - described later in this chapter - would take several more years; unfortunately, the stigmatizing association of AIDS with Haitian heritage persisted for many years beyond that.) For all intents and purposes, AIDS was a uniformly fatal diagnosis: the reported mortality rate was at least 50%, but the death rate continued to rise with time from the original identifying illness - the average survival time after the diagnosis of AIDS was only between 9.5 and 22 months. Most worrisome was evidence of a prolonged asymptomatic but contagious carrier state that suggested the number of potentially infected patients far exceeded current reports. In addition, the possibility' that the virus had contaminated the blood supply indicated a large new group of individuals at high risk. AIDS was a rapidly expanding epidemic, without an identified cause and with no effective treatment.
To this time, the general public had primarily seen AIDS as a mystery disease of gay men and drug addicts chased by epidemiologists in relative obscurity. With spread to women, babies and healthy people receiving routine blood transfusions, AIDS was suddenly a focus for the mainstream media and a cause of mounting public concern. At that time, the field of medicine was enjoying a genuine sense of accomplishment. In addition to the dramatic progress made in the development of antibiotics for treatment of infectious diseases, the twentieth century had seen major advances in almost every other area of medicine including development of vaccines against diphtheria, whooping cough, tetanus, yellow fever, and polio. Insulin therapy for diabetes was discovered, transforming this previously fatal disease. The heart—lung machine had been invented allowing routine open-heart surgery'. Computed tomography (CT) scanning and magnetic resonance imaging (MRI) provided amazingly detailed views of the human body in health and disease. Kidney, liver, lung, and heart transplants were successfully performed. Against this backdrop, the emergence of a new, fatal epidemic was an unanticipated and unwelcome surprise, and a disease that was transmitted sexually and was especially common in promiscuous homosexuals was especially unwelcome at a time when the sexual revolution that began in the 1960s had only just started to make the possibility of sex outside of traditional heterosexual, married relationships acceptable.
It is hard to describe the terror that arose when AIDS was shown to potentially infect the whole population. With no identified cause and no treatment, the specter of the disease hung over the American population, fueled by media reports of seemingly random infections. Part of the rising public concern about AIDS was related to increasing media coverage, exemplified by the continuous 24-hour news reporting launched by CNN in 1980, just as the epidemic was beginning.27 A complete CNN news cycle consisted of the media reporting on some event, followed by reporting on public and other reactions to that report. News stories were presented as continuous news with constant updating, a major contrast with the previous day- by-day pace of the cycle of daily newspapers and scheduled TV news broadcasts. With spread to heterosexuals, even sporadic AIDS cases received intense, ongoing media coverage.The obvious limits of medical knowledge also fueled fear. When the epidemic began, even understanding of immune compromise was relatively limited, obtained primarily from experience with patients receiving drugs to suppress the body’s natural immune response after organ transplant or as part of the reaction to cancer chemotherapy. AIDS appeared to be uniformly fatal, often in a very short time. Media coverage often fixated on stories that sensationalized the spread of the disease.“AIDS: Fatal, Incurable, and Spreading” read a typical headline from a cover of People magazine. The article began,
In recent months doctors have reported alarming signs that acquired immune deficiency syndrome (AIDS), the terrible, incurable disease that has ravaged the homosexual community for four years, now poses a growing threat to heterosexuals. ... 500,000 to 1 million Americans are carrying the virus that produces AIDS. About 10 percent will develop the disease over five years, doctors say; meanwhile they may transmit the virus, which has a latency period of three to five years, to their sexual partners ,..28
At the time, People had a weekly circulation of 2.8 million subscribers, so the potential impact of stories like this was substantial.