In the Eye of the Storm: The Epidemiological Construction of AIDS

Gerald M. Oppenheimer

At the beginning of an article on the human immunodeficiency virus, (HIV, the putative causal agent of AIDS that he and others isolated), Dr. Robert C. Gallo observes without comment that epidemiologists had named the new disease "acquired immune deficiency syndrome."^[1] By attributing the power to name the disorder to them, Dr. Gallo shows us how prominent a part epidemiology has played in defining and ordering this "medical mystery."

In this chapter I examine the role of epidemiology in characterizing HIV infection.^[2] Faced with a new disease of unknown origin, epidemiologists and their collaborators constructed, over time, hypothetical models to explain the disorder in order to contain it. Prior to the isolation of a putative causal agent, HIV, epidemiologists played a central role in defining the new syndrome, first developing a "life-style" model and, later, a model based on hepatitis B. Although later supplanted from their special position by virologists and other "bench" scientists working in laboratories, epidemiologists have continued to define important dimensions of the disorder and to raise disquieting questions. Specifically, they were concerned with defining the natural history of HIV infection, the extent to which it had spread within population groups, and the factors that affected the rates of disease—factors beyond the virus itself.

Epidemiology, unlike virology, has a strong social dimension in that it explicitly incorporates perceptions of a population's social relations, behavioral patterns, and experiences into its explanations of disease

processes. Given their training, epidemiologists fairly consistently defined HIV infection as a biological process occurring within a determinate social matrix. That the infection was first identified among young, male homosexuals and intravenous drug users certainly reinforced that professional proclivity.^[3]

The results of this exercise in epidemiological imagination were complex and equivocal. On the one hand, the epidemiologists' approach may have skewed the choice of models and hypotheses, determined which data were excluded from consideration until later in the epidemic, and offered scientific justification for popular prejudice, particularly against gay men. On the other hand, the epidemiological approach gave the new disease a human face. By defining the behaviors and the multiple social experiences of groups as risk factors for the disease, epidemiology countered attempts to reduce the etiology of HIV infection to a virus alone. In addition, epidemiology offered the possibility of primary prevention in the form of health education and follow-up, particularly important in the absence of a vaccine or a successful therapy.

The various characterizations of HIV infection examined in this essay will span the period from early 1981, when physicians first encountered anomalous medical facts, to mid-1987, when epidemiologists had begun to work out the causal associations between a new retrovirus isolated in 1983-1984 and the natural history of the new disease. This chapter draws almost entirely on the medical literature of the period.

Epidemiology and Public Health

Epidemiology played a key role in the AIDS epidemic for at least two reasons, one institutional, the other scientific. The institutional link was the Centers for Disease Control (CDC) in Atlanta. Part of the Public Health Service, which falls under the jurisdiction of the U.S. Department of Health and Human Services, the CDC is responsible for, among other things, monitoring morbidity and mortality trends in the United States and for responding to acute outbreaks of disease—infectious disease in particular. The CDC depends heavily on case reports, surveillance, and epidemiological investigations in order to fulfill its mission. Its investigations are conducted both by the permanent staff and by officers in the Epidemic Intelligence Service (EIS), who are young physicians or Ph.D.s who exchange two years of service for training in epidemiological techniques.

Epidemiology, in comparison with most other medical disciplines, is particularly well-suited to explore, portray, and explain new medical phenomena. It seeks to measure and analyze the occurrence and distribution of diseases and other health-related conditions, acting both as a sentinel who warns of shifts in disease patterns and as a scout who seizes on such shifts to discover their etiology.^[4]

For example, by systematically collecting data on the frequency of disorders in populations or subgroups through surveillance programs, epidemiologists can discern changes in the distribution of diseases in the community. Observations of these distributions, and their variation in subgroups, lead to hypotheses concerning the relationship between the disease and variables that may affect its natural history and clinical course. Using various study designs, epidemiologists attempt to measure, reject, or refine the relative significance of such hypothetical associations. The ultimate objective of these studies is to isolate the causal variables of the disease in question. An intermediate goal is to discover a point in the natural history of the disease where intervention might alter its course, even if its etiology remains unknown.^[5]

Epidemiologists tend to believe in multifactorial disease models. They assume, that is, that intervention is possible at several points, even in the absence of a known "first cause." The major premise of the multifactorial model is, as the name implies, that a given disease may have a number of causes or antecedents, a combination of which may be needed to produce the disorder. The "web of causes," therefore, may be interdicted at more than one vulnerable point.^[6]

The power of the multifactorial model is that it can incorporate any measurable factor relevant to and statistically associated with the disease or disorder of interest. Unlike the reductionist paradigm of the germ theory, the multicausal model embraces a variety of environmental and social factors. The model's strength, however, is also its weakness. The multifactorial model allows the researcher to cast a very wide net. Scientists may attempt to incorporate many possible explanatory variables whose putative causal connections with a given disease may be plausible for a number of reasons—scientific, logical, historical, experiential, and so forth. Variables may be drawn in (or left out) as a function of the social values of the scientist, the working group, or the society. When included in the model, embraced by the professionals, and published in the scientific press, such value judgments appear to be objective, well-grounded scientific statements.

Epidemiology is an applied science that responds to two kinds of disorder within the community, one caused by the disease directly, and the other the product of the very fears it has aroused. Consequently, epidemiology bore the initial responsibility of outlining the direction of research, of generating hypotheses, and of synthesizing the results. In the face of a fatal disorder of unknown origin and indefinite proportions, such as HIV infection, epidemiology offered a set of procedures (e.g., case definition, verification, and count) that swiftly generated results and then authenticated them, giving the public a sense of definite progress. The content of this science, by providing and naming concepts ("risk groups," "life-style hypothesis"), made the epidemic potentially less frightening by making it appear more likely that it would eventually be known and controlled.

Case-Finding and Surveillance

The initial discoveries heralding a new disorder of unknown origin were made by physicians treating patients in Los Angeles. Dr. Michael Gottlieb and his colleagues alerted the CDC that between October 1980 and May 1981 five young, previously healthy homosexual men had been treated in local hospitals for biopsy-confirmed Pneumocystis carinii pneumonia (PCP). Two of the patients had already died. An investigation by an EIS officer confirmed the diagnosis of PCP, a protozoan-produced condition that occurs almost exclusively in persons with severely suppressed or defective immune systems. On June 5, 1981, a short paper describing the patients was published by the CDC in its Morbidity and Mortality Weekly Report (MMWR ).^[7]

Gottlieb's communication to the CDC was closely followed by another from both New York City and San Francisco, which reported that in the thirty months prior to July 1981, Kaposi's sarcoma (KS) had been diagnosed in twenty-six male homosexuals between twenty-six and fifty-one years of age.^[8] A rare cancer in the United States, KS had historically occurred in this country primarily in elderly males and immuno-suppressed transplant recipients. Its manifestation in a relatively large number of young men was considered highly unusual, as was the appearance of PCP in individuals without a clinically apparent cause for immunodeficiency disease.

An editorial note in the MMWR issue that had published Gottlieb's paper hypothesized that "the fact that these patients were all homosexuals suggests an association between some aspect of a homosexual life-

style or disease acquired through sexual contact and Pneumocystis pneumonia in this population."^[9] The conjecture that some aspect of homosexuality predisposed the patients to immune dysfunction and infections was made on the basis of five cases from a single community—a broad generalization indeed to formulate from so small a sample.

The basis for that sweeping hypothesis lay in a rough mixture of analysis and opinion. The CDC had just completed a cooperative study with a number of gay community health clinics. It was a multiyear, multisite study of risk factors for hepatitis B, a disease that can be sexually transmitted and whose prevalence is very high among homosexual men.^[10] In analyzing the interrelation of life-style and hepatitis B, the researchers found that blood markers for the disease were significantly associated with, among other factors, the number of male sexual partners and with sexual practices that involved anal contact. On average, the subjects tended to have a high mean number of partners. Nonetheless, because these were younger men (with a mean age of twenty-nine years), all of whom were attending clinics that specialized in sexually transmitted diseases, they were not necessarily representative of homosexual men.

The CDC-associated study took place against a background of other investigations that suggested an increase in the incidence as well as the types of sexually transmitted diseases (STDs) in homosexual men.^[11] Analysts linked this epidemic of STDs among gay men to gay liberation and the attendant life-style of bars, discos, and bathhouses and of anonymous sexual partners.^[12] These charges reinforced a set of assumptions, often expressed in medical texts (discussed in greater detail below) by venereologists, that gay men, because of their "pathetic promiscuity" and supposed hedonism, are more vulnerable to sexually related diseases than are heterosexual men and women.^[13]

The combination of the CDC's recent work on risk factors for hepatitis B transmission, which had increased its awareness of gay sexuality, and its knowledge of the epidemicity of STDs among subgroups within the gay community, probably accounts, in part, for the hypothesis suggested in the MMWR . A greater awareness of homosexual life-style and disease patterns alone cannot explain the CDC's proposal of a hypothesis on the strength of so few actual cases and without seeking evidence that other segments of the U.S. population might be at risk. One might fairly infer that the CDC was prematurely ready to find the etiology of this mysterious disorder in an exotic subculture. This inference is strengthened by the ensuing scientific work undertaken by epidemiologists within and outside the CDC to find in gay culture—particularly in

its perceived "extreme" and "nonnormative" aspects (that is, "promiscuity" and "recreational" drugs)—the crucial clue to the cause of the new syndrome.

Part of the reason for the CDC's speedy adoption of the "life-style" hypothesis was, most likely, that in certain previous outbreaks of diseases of uncertain origin (in particular, Legionnaires' disease in 1976), CDC officials had been criticized for having committed themselves too strongly to a microbial hypothesis without having paid sufficient attention to alternative causative theories.^[14] This probably influenced their desire to throw a wide causative net in the case of HIV infection.^[15]

A special task force on KS and opportunistic infections was established at the CDC in mid-1981 and charged with the surveillance of all new cases. According to Dr. James W. Curran, head of the task force, the purpose of surveillance was to confirm that the observed disorder was new, that it was occurring in the specific populations and geographic areas reported, and that all cases were verified.^[16]

Prior to surveillance, the CDC had to define what constituted a case. It initially described a case as "a person who (1) has either biopsy-proven KS or biopsy-proven, life-threatening opportunistic infection, (2) is under age 60, and (3) has no history of either immunosuppressive underlying illness or immunosuppressive therapy."^[17] By September 1982, when the CDC first used the term "AIDS" in the MMWR , it refined this description to define an AIDS case as one with "a disease 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." Included among the diseases were KS, PCP, and a specific list of "other opportunistic infections," a list that the CDC has amended over the years.^[18] The surveillance definition, whose prime purpose is to assist national reporting of the disorder, has, with as much precision as possible, been limited to the more severe manifestations of the disease.^[19]

To establish a count of, and to verify, all cases, the task force and EIS officers conducted a letter and telephone survey of physicians in eighteen U.S. metropolitan areas. In addition, by August 1981 all state health departments had formally been asked to notify the CDC of all suspected cases.^[20]

To determine if Kaposi's sarcoma had occurred before 1980 in individuals less than sixty years of age, the task force contacted epidemiologists at state or local tumor registries. Because the CDC was the sole supplier of pentamidine, a drug used in the treatment of PCP, its own files could reveal whether the infection had been seen in adults

without underlying illness. Both investigations suggested that the disease was new, the first documented community-acquired epidemic of immunosuppression.^[21]

What caused this disorder? With limited clinical data at hand, the CDC did a "quick and dirty" survey of 420 males attending STD clinics in San Francisco, New York, and Atlanta with the intention of finding cases with KS or PCP. The thirty-five cases culled from the sample (biased, or unrepresentative, in that such patients may be more active sexually than the general population) were interviewed on many subjects in the hope that a lead might be discovered.

The researchers found two patterns of behavior that "fell out": sex and drugs. The cases, all homosexuals, had had many sexual partners in the past year (the median number of partners was eighty-seven) and had frequently used marijuana, cocaine, and amyl or butyl nitrite—inhalant sexual stimulants.^[22] Were sex and drugs independent of each other, however? The rate of nitrite use, for example, was closely associated with the number of sexual partners, suggesting that nitrite inhalation might be associated with other hypothetical causal variables, including STDs or the medications used to treat them, or types of sexual behavior, or attendance at gay bathhouses.^[23] It was also possible that nitrite use was not an etiological factor, but appeared to be one because it was associated with a causal, or "confounding," variable like sexual behavior.

"There are a lot of theories . . . at the start," James W. Curran is quoted as saying:

You get heterosexual doctors examining gays, and they jump on the first possible hypothesis, that it must be due to the sexual behavior of homosexuals. Because gays are involved, there is also the assumption that they are doing drugs. There were suggestions that it had something to do with amebiasis, a type of dysentery that poses a particular threat to gay men because the guilty protozoa can be spread through anal contact. There wasn't any evidence for this either.^[24]

Despite the dearth of clinical evidence, amyl nitrite (AN) became one of the first hypothetical causal variables to be investigated. The "quick and dirty" survey had found that 86.4 percent of homosexual or bisexual men had used nitrite in the previous five years, compared to 14.9 percent of male heterosexuals.^[25] As a clue, amyl nitrite seemed worth pursuing, particularly as it appeared to be a component of the "gay life-style" thesis that was posited in the MMWR and was riveting the epidemiological researchers. Studies in which nitrite inhalant was a variable will be evaluated below.

Published scientific papers in 1981 were mainly case and surveillance reports—attempts to define the new syndromes and the patients, that is, to formulate what constituted a "case." By describing the population at risk in terms of person, place, and time, and by learning from physicians the clinical details of the disorder, epidemiologists could grope for etiological clues they might use to design formal studies.

One of the first clinical clues the CDC pursued was the possibility that the new syndrome was caused by the cytomegalovirus (CMV), a microbe suspected of being both sexually transmitted and a cause of KS. In September 1981 the British medical journal, The Lancet , published a clinical study of Kaposi's sarcoma in eight homosexual men hospitalized in New York City; the investigation found that of four patients tested, all were positive for CMV.^[26] Three months later Michael Gottlieb and his colleagues reported in the New England Journal of Medicine that four previously healthy men with PCP were both infected with cytomegalovirus and were suffering from a marked decrease in white blood cells, particularly of a kind known as "T4 helper cells."^[27] Although acknowledging that CMV infection might result from T4-cell deficiency and the reactivation of a dormant infection, Gottlieb and his colleagues preferred to hold CMV highly suspect. Their position was based on previous studies that had shown that exclusively homosexual men had a higher rate of CMV infection than heterosexual men attending the same STD clinic (94 percent versus 54 percent), that the virus could shed in the semen for prolonged periods of time, and that some evidence existed that CMV produced immunosuppression. Consequently, the authors reasoned that CMV might be responsible for immune-system defects, leaving its victims susceptible to opportunistic infections such as PCP and to cancers such as Kaposi's sarcoma.

CMV was also cited by the CDC as one of three possible etiological agents in its year-end summary on the epidemic.^[28] Other putative causes, perhaps more closely related to the "life-style" hypothesis, were amyl nitrite and opiate addiction (a recent investigation of eleven immuno-compromised men with PCP treated in New York City had found that seven of the patients, including five heterosexuals, were drug "abusers"^[29] ). Did any of these agents bear a relationship to any other? How did CMV fit into the "life-style" hypothesis? An editorial in the New England Journal of Medicine addressed these issues in December 1981.

Ignoring the heterosexual cases of PCP and other opportunistic infections, the editorialist noted that "the question of cause is obviously central. What clue does the link with homosexuality provide?",^[30] positing

that the answer was a high incidence of sexually transmitted diseases, including viral infections such as CMV and hepatitis B, which might cause immunosuppression and KS. But because neither homosexuality nor CMV is new, the author suggested that a new factor may have modified the host-agent relationship: recreational drugs, particularly amyl nitrite. Based on this reasoning, he postulated a possible multifactorial disease model,^[31] proposing that the joint effects of persistent, sexually transmitted viral infection (presumably from CMV) and a recreational drug like amyl nitrite precipitated immunosuppression in genetically predisposed males. From this followed a clinical course that included minor illnesses, then KS or other neoplasms, and serious opportunistic infections. In essence, the model was an elaboration of the hypothesis originally proposed in the editorial note appended to the first MMWR on the new disease.

The "Life-Style" Hypothesis: Experimental Work

To refine hypotheses generated by case reports, "quick and dirty" surveys, and surveillance, researchers compared patients with a group of healthy men possessing comparable sociodemographic characteristics, experiences, or behaviors. Such research designs, which begin with outcome (the disease) and attempt to discover factors retrospectively that can account for the different health status of the two groups, are known as "case-control studies." The early case-control studies were meant, in part, to test whether suspected agents like CMV or amyl nitrite might be causative factors.

One of the first such studies, by James Goedert and his colleagues at the National Institutes of Health (NIH) and the Uniformed Services University of the Health Sciences in Bethesda, Maryland, explored the relationship between KS and amyl nitrite.^[32] Goedert attempted to assess the new disorder (the outcome) by collecting clinical, virological, and immunological information on two male homosexuals with KS and fifteen healthy homosexual volunteers. The researchers hypothesized that CMV hyperinfection and / or the chronic use of amyl nitrite might be causal variables. In presenting their results and assessing the implications, the investigators suggested that amyl nitrite inhalation may predispose homosexual men to immune deficiency.^[33]

This investigation had some serious limitations. The small number of subjects in the study, for example, deprived it of the power to find statis-

tical significance if significance existed. Moreover, there was no internal evidence to link CMV with Kaposi's sarcoma or amyl nitrite. Though amyl nitrite was correlated with immune defects, the researchers did not report any controls for the effects of possible "confounders," that is, alternative causal variables such as the number of sexual partners, duration of homosexual experience, or any other proxy for infectious transmission of a disease. Notwithstanding its defects, the study by Goedert and his colleagues was cited by others as evidence for the plausibility of amyl nitrite as a causal variable, a tribute, in part, to the power of the "life-style" hypothesis.^[34]

Almost simultaneously with the investigation by Goedert and his colleagues in Bethesda, researchers in New York City interviewed twenty gay men with biopsy-confirmed KS and forty gay male controls, matched for age and race, eliciting information on sociodemographic characteristics, medical history, sexual practices, and drug consumption. The cases were twenty of the twenty-one men, aged fifty-two or younger, with biopsy-confirmed Kaposi's sarcoma attended to by New York University Medical Center between March 1979 and August 1981. Controls were selected from the private patients of a Manhattan physician who mainly treated homosexual men. A third of those asked to be controls refused, raising the possibility that the control group was skewed in some indeterminate way. Using multivariate analysis, the investigators found that of all the study variables, only amyl nitrite and "promiscuity" (as measured by number of different sexual partners per month in the year before onset of disease) appeared to have an independent, statistically significant association with KS. The results, like those of Goedert's, were published in the Lancet , under the title "Risk Factors for Kaposi's Sarcoma in Homosexual Men."^[35]

In October 1981, which was approximately when the New York City investigation began, the CDC undertook a multisite case-control study to identify risk factors for Kaposi's sarcoma and Pneumocystis pneumonia in gay men who lacked predisposing clinical factors for either. The results of the study were published in August 1983.^[36] Its authors chose as controls male homosexuals without KS or PCP, matched to the cases by age, race, and metropolitan area of residence. Mindful that private-practice controls might not be drawn from precisely the same population, with equal risk of exposure to any number of factors as the cases, the researchers used, where possible, multiple controls—that is, patients from both private practice and STD clinics.

The study found that KS and PCP were associated with certain aspects of male homosexuality, in particular, numerous sexual partners per year. Other significant variables were attendance at bathhouses, a history of syphilis, the use of illicit drugs (excepting nitrites), and exposure to feces during sex. The strong implication was that a subgroup of the male homosexual population, those who were most sexually active, were at greatest risk for KS or PCP. Based on the appearance by then of similar opportunistic diseases in other segments of the U.S. population, including hemophiliacs, the authors concluded that an infectious agent might be the necessary cause.

Nonetheless, the CDC was unwilling to disengage itself from the "life-style" hypothesis or to commit itself to a microbe theory alone. In the second part of the study report, the authors summarized that position: "Although the cause of the acquired immune deficiency syndrome in homosexual men remains unknown, the study presented here and in the companion paper has identified a distinctive lifestyle as an important risk factor."^[37]

In their exploration of the "life-style" model, CDC researchers asked detailed questions regarding diet, residence, drugs, and sex, then generated hypotheses based on the associations discovered. As KS and PCP were first seen in persons identified by their sexual orientation, research into sexual behavior followed logically. But the term "promiscuity" implied more than this; it implied moral judgment. Why was this term used so frequently in scientific articles? The Marmor study of 1982, for example, repeated the term "promiscuity" six times.^[38]

Promiscuity denotes behavior that is casual, careless, indiscriminate, or irregular. "Irregular" means behaving without regard for established laws, customs, or moral principles, failing to accord with what is usual, proper, accepted, or right.^[39] Not surprisingly, the term has been closely associated with sexuality, referring to persons who willfully violate the moral code, who lack self-control. The notion of promiscuity has been applied to groups at the "margin" of society, those who, like immigrants, the working class, the criminal, or blacks, are also seen as intemperate and prone to disease.^[40]

Despite its heavy moral freight, "promiscuity" is traditionally used in medical texts to signify sexual behavior involving multiple partners. For example, in an important article in Annals of Internal Medicine in 1975, researchers reported the results of a retrospective study testing the validity of the hypothesis that serum hepatitis might be sexually

transmitted. In the monograph, five subpopulations were compared, including one composed of male homosexuals and one of male and female heterosexuals attending STD clinics in New York City. In the body of the article and in the initial abstract, both groups are described as "high promiscuity populations," although gays are singled out by the statement that "a well-known feature of homosexual behavior, primarily in men, is an extraordinary degree of sexual promiscuity," with the Kinsey work on Sexual Behavior in the Human Male cited as evidence.^[41]

Other examples can be adduced. An article published in the British Journal of Venereal Disease in 1976 states that "the high proportion of homosexuality among men with syphilis and gonorrhoea has been ascribed to such factors as the promiscuous behavior of homosexuals."^[42] A 1981 study in the same journal comments that "male homosexuals appear to be more prone to these [venereal] conditions than female heterosexuals because a large minority are indiscriminately promiscuous."^[43]

Although it appears often in a "clinical" context, the concept of "promiscuity" retains its moral dimensions, even in a medical dialogue or text. For example, Dr. Joyce Wallace, an internist and AIDS researcher interviewed by the Journal of the American Medical Women 's Association in 1982 observed that "during the last year we have become aware of an unusual number of infections and cancers in formerly healthy homosexuals who admit to a promiscuous lifestyle."^[44] She went on to say that "both monogamous homosexuals and those who are not sexually active have absolutely normal [T cell] ratios. It seems to be the promiscuity that's the culprit."^[45] When asked "what does this epidemic mean?", she responded: "That promiscuity can kill you. These people don't have enough T-lymphocytes to ward off serious diseases such as tuberculosis, Pneumocystis carinii pneumonia or Kaposi's sarcoma."^[46] In brief, as the title of the piece suggests ("Medical Sequelae of a Lifestyle"), the predisposing cause of the epidemic appeared to be unbridled behavior as much as a microbe or immunosuppression.

Sensitivity to the use of "promiscuity" in a clinical context was expressed in a letter to the Journal of the American Medical Association by two members of the American Association of Physicians for Human Rights, an organization consisting primarily of gay doctors. The writers noted that the use by medical personnel of a term like profound promiscuity to describe multiple sex partners was strongly judgmental. It did not belong in the scientific medical literature, and its continued use adversely affected homosexual patients, who hesitated to

discuss sexually related issues frankly with their physicians, fearing their disapprobation.^[47]

"Promiscuity" as a moral expression implied that the patients bore direct responsibility for their condition. Integrated into the life-style model, the term inadvertently muddied an already difficult inferential problem; namely, whether the risk factors isolated by researchers were indirect causes of the disease, lone direct causes, or cofactors. In effect, the use of the term "promiscuity" confused a scientific problem (what factors are causally responsible? ) with a moral and political one (who is accountable? ). Perhaps more important, use of the term reflected how skewed the life-style model had become; that is, the degree to which its adherents had limited the spectrum of patients to homosexual men.

The first heterosexual patients, including the first woman, were reported by the CDC in August 1981.^[48] The first clinical descriptions of immunosuppression in heterosexual intravenous drug users appeared in December 1981.^[49] By June 1982 the MMWR had reported that 22 percent of patients with KS and / or PCP were heterosexuals, the majority intravenous drug users.^[50] Almost a third of the heterosexual patients were women. Despite the early appearance and growing number of heterosexual patients, epidemiologic studies of this group were significantly underrepresented in the literature prior to 1984.^[51]

Would investigations of heterosexual patients, paralleling those done of gays, have offered a different cast to the life-style model? We will never know for certain. The model probably would have placed less emphasis on multiple sexual partners, on "promiscuity." Perhaps chemical toxicity or the immunosuppressive power of heroin, nitrites, and other drugs might have had more significance, at least at the start. But inasmuch as women—some of whom were not intravenous drug users—were among the earliest patients, investigators might possibly have hypothesized much earlier on that a microbe was the direct cause, explaining the appearance of the new disorder in all affected groups.

Why, we might well ask, were heterosexual intravenous drug users not studied? There is no simple answer. One reason, a structural one, is that at the federal level the National Institute of Drug Abuse (NIDA) had principal responsibility for investigating issues related to intravenous drug use and had a staff of epidemiologists just for that purpose. NIDA's traditional focus, however, was only on drug abuse, eschewing investigations of diseases such as hepatitis B and endocarditis that were endemic or epidemic in their target populations. The leadership of

NIDA decided that AIDS would be treated like any other disease, thereby leaving the research initiative to other centers at NIH or the CDC.^[52] Unfortunately, the CDC, lacking previous experience and expertise, shied away from studying the drug-using population, leaving a lacuna.^[53]

Another reason drug users were not studied was the relatively small number of research subjects available, particularly outside the New York metropolitan area.^[54] That problem was alleviated, however, by the development during the summer of 1984 of a blood test measuring antibodies to HIV. The test created a much larger pool of potential research subjects by identifying individuals who were infected but who did not have AIDS or serious, related illnesses.^[55]

A final answer to the question posed was the unwillingness of epidemiologists to study this group.^[56] Partly justified by the disinclination of addicts to cooperate in interviews and with follow-up, it may also, in part, be explained by a feeling among many clinicians and researchers (in this respect reflecting the attitudes of the public at large) that addicts are of less social consequence than other patients.^[57] In a striking reflection of that lack of interest, at all levels of government and in the universities few epidemiologists had expertise in drug addiction when the HIV epidemic began.

Despite its appeal, the life-style hypothesis was eventually undercut as a sufficient explanation. During 1982 epidemiological surveillance and case reports made it clear that in addition to homosexual males, others were at risk for AIDS. As an article in JAMA observed in September of that year: "If lifestyle is the key, the question still remains: Why has AIDS also occurred in heterosexual men (84 cases so far), women (32 cases so far), mostly heterosexual Haitians, and hemophiliacs?"^[58] A new model was required.

An Unknown Transmissible Agent

On March 4, 1983, after a year of suggestive data, a Public Health Service interagency report (published in the MMWR ) marked a major shift in the conceptualization of the disorder.^[59] What caused that shift was in part the kind of evidence cited by JAMA : Case reports to and surveillance by the CDC made it clear that the disease was more than a syndrome of homosexual men and promiscuity.

On July 9, 1982, the CDC had reported that thirty-two Haitian immigrants to the United States, seven of them women, showed immu-

nological, morbidity, and mortality patterns similar to those in homosexual men and intravenous drug users.^[60] Although the MMWR had previously published two general updates on the increased incidence of the new disease—updates that had included data on heterosexual patients—the article on Haitians constituted the first complete report focusing directly on persons outside the "homosexual" category.

A week later, and again in December 1982, the MMWR alerted its readers that patients with hemophilia but no other underlying disease had contracted PCP.^[61] The CDC observed that inquiries concerning the patients' sexual activities, drug usage, travel, or residence offered no evidence that the cases were in contact with each other, with homosexuals, intravenous drug users, or Haitian immigrants. What the hemophilia patients shared was a dependence on Factor VIII, the clotting substance they lacked, usually derived from the pooled blood of two thousand to twenty thousand donors.^[62]

The possibility of blood as a vector for AIDS was heightened by a CDC report of unexplained immunodeficiency and opportunistic infection in a twenty-month-old infant who had received multiple transfusions, including platelets from a donor subsequently diagnosed with AIDS.^[63] The sibling of the infant was in good health and his parents were described as "heterosexual non-Haitians" without a history of intravenous drug use.

Summing up the new cases, the March 4 MMWR observed that current epidemiological data indicated four groups were at increased risk of contracting AIDS: homosexual men with multiple sexual partners, users of intravenous drugs, Haitians who had emigrated to the United States in the previous few years, and hemophiliacs. In addition, unexplained immunodeficiency and life-threatening opportunistic infections had occurred in the female sexual partners of bisexual or intravenous drug-using men, and the children born of their unions.

Instead of life-style, the report hypothesized that the cases shared exposure to a transmissible agent. Though the agent was unknown, the pattern of cases mimicked that of a known pathogen, one that epidemiology had studied and helped control in the years before AIDS:^[64]

The distribution of AIDS cases parallels that of hepatitis B virus infection, which is transmitted sexually and parenterally. Blood products or blood appear responsible for AIDS among hemophilia patients who require clotting factor replacement. The likelihood of blood transmission is supported by the occurrence of AIDS among IV drug users. Many drug abusers share contaminated needles, exposing themselves to blood-borne agents, such as hepatitis

B virus. Recently an infant developed severe immune deficiency and an opportunistic infection several months after receiving a transfusion of platelets derived from the blood of a man subsequently found to have AIDS.^[65]

In adopting the hepatitis B analogy, epidemiologists posited an alternative organization of known variables, one which stressed a biological agent whose vector was blood and/or its constituents. Although "life-style" factors could be incorporated, they had lost some of their cachet. In the CDC national case-control study, for example, Harold W. Jaffe and his colleagues, reporting their results in August 1983, suggested that life-style factors are indirect causes of AIDS, with a microbe, probably a virus, as the direct cause.^[66]

Although epidemiologists had not yet identified an agent, the model of hepatitis B supported the introduction of public health measures. Stated somewhat differently, the model offered a putative point of intervention in the multifactorial "web of causes," even in the absence of a known pathogen. Recommendations previously developed for hepatitis B were applied, with the Public Health Service recommending no sexual contact with persons suspected or known to have AIDS. In addition, members of groups at risk were asked not to donate blood or plasma, and doctors were encouraged to recommend autologous transfusions to their patients. Finally, the Public Health Service called for the development of blood-screening procedures.

On March 4, 1983, for the first time in the MMWR , the CDC referred to "high-risk groups," attesting to the spread of AIDS into multiple segments of the U.S. population and to the relationship between the concept of "high-risk group" and hepatitis B. High-risk groups were those whose members were at greater risk of infection and of infecting others, carrying a microbe that was capable of spreading through sexual and blood-borne traffic. The MMWR underscored that "each group contains many persons who probably have little risk of acquiring AIDS."^[67] Nonetheless, no calibration of degree-of-risk was introduced, so no distinction could be drawn. As no microbe had been isolated, risk designation was, in effect, synonymous with carrier status, even among scientists, not to speak of the news media and among the general public.

Some months later the CDC justified its use of risk groups, arguing that classification of individuals was intrinsic to any epidemiological investigation.^[68] Classification should not be taken to mean, however, that groups at higher risk for AIDS could transmit the disease through non-intimate contact, because casual transmission was a view unsupported

by available evidence. To use the likelihood of casual transmission as a basis for social and economic discrimination was unfair.

The apology of the CDC missed the point. Grouping individuals may be traditional in epidemiology, both as a means of intervention and as an analytic prerequisite. The political or social consequences of such grouping are rarely examined. In this instance, even if the fear of casual transmission could be eradicated, the groups identified would still be seen as bearing a strong negative relationship to the life-sustaining blood supply. They were created, qua groups, to signify their potential status as carriers of tainted blood and as contaminators. Moreover, the analogy with the highly contagious hepatitis B virus reinforced the association of casual or vertical transmission, particularly for health-care providers, because hepatitis B is transmitted through close personal contact, through all secretions, through wounds and lacerations.^[69]

A further consequence of creating "high-risk groups" was to reinforce the relationship between the disease and "marginal" members of the population. This tendency to attribute blame for disease to socially marginal groups is discussed in greater detail in the chapters by Guenter B. Risse, Elizabeth Fee, and Paula A. Treichler. In the case of HIV, although each of the groups ostensibly threatened the remainder of the community through the medium of blood or sex, public health recommendations were intended to inhibit such contamination. Consequently, the disorder could be contained at the boundaries, among people who were "different" from the majority but undifferentiated within each of the "high-risk groups."^[70]

One of the dangers of a scientific classification of people based on stereotypes was that it defined the questions raised and thus answered. Such categorization created a Procrustean mind-set evident from the beginning of the epidemic. In early 1982 researchers, in an act of political and scientific oversimplification, designated the new disorder with the acronym GRID (gay-related immunodeficiency), even though the CDC and the New England Journal of Medicine had published reports of heterosexual intravenous-drug-using patients with the new syndrome. At a major conference Michael Gottlieb and his colleagues could report, in a paper entitled "Gay-Related Immunodeficiency (GRID) Syndrome: Clinical and Autopsy Observations," that of the ten adult males in the study with the syndrome, two were exclusively heterosexual.^[71]

In 1983, when researchers seriously began to consider the diagnosis of AIDS in patients outside the previously defined high-risk groups, they attempted to fit them into the current categories. How, for example,

should children with immune-deficiency syndrome be categorized? One approach was to link them to established classifications through their mothers, who were characterized as either drug-addicted or, like gay men, promiscuous.^[72] Although the researchers did not define promiscuity, it was assumed to exist and to be directly or indirectly explanatory. One subject, "the mother who denied sexual promiscuity or drug addiction," therefore left a lacuna in the case report.^[73]

A second article, appearing in the same issue of the Journal of the American Medical Association (JAMA ), offered an alternative explanation of the same phenomenon. Noting that "until recently, AIDS seemed to be limited to adults, predominantly in those with aberrant life styles or exposure to blood products," the authors observed that the children each experienced "household exposure" to one or more individuals in the high-risk groups, including homosexuals, Haitians, and intravenous drug users.^[74] As no evidence existed that the children had either been drugged or sexually abused, the investigators proposed the possibility that the patients had been infected through routine close contact. When Anthony Fauci of the National Institute of Allergy and Infectious Diseases repeated the hypothesis in an editorial in JAMA , he raised a firestorm of public fear and confusion.^[75]

Ultimately, the hepatitis B metaphor assumed the existence of a highly contagious, infectious agent, probably a virus. Though some favored a new variant of the cytomegalovirus, others, including James W. Curran of the CDC task force, supported the notion of a new infectious agent.^[76] In the long run, either hypothesis rested on detecting a pathogen that had hitherto proved elusive.

AIDS: "The Story of a Virus"

From 1981 until the isolation of a new virus, epidemiology played a central role in the characterization of HIV infection. That discipline, using specific case definitions, surveillance, and case-control studies, identified "high-risk groups" and offered suggestive models and similes. Although epidemiology formulated the social context and morphology of the new disorder, it could not discover its microbial cause. That function was filled by virologists at the Pasteur Institut in Paris and in laboratories in the United States, at the National Cancer Institute (NCI) in particular.

In May of 1984 the journal Science published four reports authored by Robert C. Gallo of the NCI and his colleagues and a fifth by Luc

Montagnier of the Pasteur Institut.^[77] These reports established a strong case for a causal link between AIDS and a newly discovered retrovirus that the NCI called HTLV-III and the French called LAV. Later, an international agreement was made to call the retrovirus human immunodeficiency virus (or HIV).

With the isolation of this putatively causal virus, the relative importance of epidemiology in the definition of the disease lessened. Epidemiologists continued to play an important, although somewhat more peripheral role, providing supporting evidence for the viral hypothesis and developing information in areas outside the reach of microbiology and its techniques.

Increasingly, the "bench" scientists—virologists, immunologists, cancer researchers—determined the definition of HIV infection. In effect, they redefined AIDS as a set of biomedical problems open to a chemical resolution in the form of drugs and vaccines. These scientists removed the disorder to a considerable degree from the stigma of its original social matrix, placing it instead into a context resembling that of the supposedly more purely clinical crusades against cancer or polio.

The change in the type of professionals studying HIV infection and in their defined fields of observation and analysis effected a subtle shift in the characterization of the disorder. The disease was increasingly conceptualized in terms of the infectious agent, the virus. Interest in cofactors or a multifactorial model diminished.^[78]

One marker of this shift was the title of a book copublished by the Institute of Medicine and the National Academy of Sciences in 1986: Mobilizing Against AIDS : The Unfinished Story of a Virus ;^[79] four years earlier an article in JAMA had observed that "it seems unlikely that a virus alone is inducing AIDS."^[80] Another marker was the dearth of studies on cofactors—of events or states independent of the virus but necessary to cause HIV infection in general or AIDS in particular. In early 1987 an article prospectively evaluating cofactors for HIV could cite only one published report on cofactors after 1984.^[81] A few months earlier another volume cosponsored by the Institute of Medicine and the National Academy of Sciences, although acknowledging the importance of cofactors, suggested "there are no data to support the concept [of cofactors], with the possible exception of genital ulcers in Africa."^[82] The authors called for well-controlled laboratory and epidemiologic investigations.^[83]

The increasingly biological definition of the disease was reinforced by the successful development of serological procedures for the detection

of antibodies to the virus. These tests—the enzyme-linked immunosorbent assay (ELISA) and the Western blot technique—allowed epidemiologists and other scientists to outline the biological parameters of the new disorder.

A first step was to demonstrate that the newly discovered retrovirus was the cause of AIDS. To do so, studies cumulatively had to meet the current formulation of Koch's postulates.^[84] The first two postulates—(1) that a specific viral pathogen, or its particles, must be found in almost all patients with AIDS-like syndromes, and (2) that antibodies to the virus must form "in constant temporal association with the development of AIDS"—were partially met by the initial studies reported in Science in May 1984.^[85] The third postulate (that transmission and illness must be demonstrated in a previously uninfected person) was increasingly fulfilled by epidemiologic investigations, first, by studies of patients with transfusion-associated AIDS and their blood donors, and, second, by serological investigations of the spread of HTLV III/LAV from high- to low-risk areas.^[86]

In July 1986 the CDC reported that epidemiologists, using the new blood tests, had confirmed that persons at higher risk of AIDS in the previously defined groups showed a greater prevalence of HTLV-III/LAV viral antibody.^[87] Epidemiologists also found that AIDS and a number of less full-blown conditions, including lymphadenopathy and AIDS-related complex (ARC), had the same underlying viral cause. In addition, antibody tests demonstrated the existence of the viral infection in persons without clinical symptomatology, a not unusual pattern in infectious-disease epidemiology. These data suggested to the CDC that the spectrum of human response to the virus was wider, thus requiring careful study.^[88]

Standardized blood tests thus initially provided a biological justification for the previously defined high-risk groups. At the same time, antibody testing could distinguish within the risk groups between those who were seropositive and those who were not. As a result, group membership and carrier status could theoretically be separated. Given the logic of the biological model, moreover, the concept of high-risk membership should actually have withered away, replaced by the notion of high-risk activities that made infection more likely. Despite logic, a shift in emphasis from "status" to "act" did not occur until "mainstream" heterosexuals were targeted as a population at risk.^[89]

Since 1984 epidemiologists have also contributed to knowledge of the natural history and transmission of HIV infection. The particular

strength of epidemiology in these areas has in part derived from the "bench" scientists' inability to uncover suitable nonhuman animal models, and in part from epidemiologists' technical ability to transcend the ethical limitations on human experimentation by studying disease patterns occurring in populations.

Overall, these epidemiologic studies are attempting to enlarge our knowledge of the biological/clinical dimensions of HIV infection, but to develop that knowledge, wherever possible, within the social matrix or behavioral history of the populations involved. By so doing, epidemiologists are maintaining the vitality of a multifactorial, social conception of AIDS in the face of a narrower biological definition.

To date, most epidemiologic studies of AIDS have prospectively followed a defined cohort of individuals, usually homosexual men. The purpose of these investigations has in general been to establish the risk factors for HIV infection or to describe the pathologic state of those already infected—to estimate, in particular, the proportion of individuals who, over time, develop AIDS. In addition to defining the natural history of the disorder, the researchers aim to find determinative variables that may be open to clinical or social intervention.

For example, Cladd Stevens and her colleagues at the New York Blood Center tested the blood of 212 volunteers for HIV in order to assess its spread and to determine the impact of any changes in sexual behavior.^[90] Part of a cohort of 4,394 male homosexuals residing in New York City who had participated in hepatitis B studies beginning in 1978-1979, the 212 had had sera drawn every six months from the time of their entry into the investigation until early 1984. Behaviors that proved to be significant predictors of HIV infection included being the receptive partner in anal intercourse and having sexual contact with a person known to have AIDS. The researchers also reported that 48 percent of the 212 had detectable antibodies to HIV in 1984, compared to 6.6 percent in 1978-1979; this resulted in an annual incidence that varied from 5.5 to 10.6 percent, but was highest in 1983 through early 1984. Because seroconversion (a positive test result indicating probable HIV infection) increased despite a reported curtailment of sexual activity by the study subjects, the authors inferred that "the risk of exposure from a sexual encounter is now much greater than it was early in the epidemic, and indicates that precautions taken by many homosexual men thus far are not adequate to prevent transmission."^[91]

Somewhat similar results were obtained in a Dutch longitudinal study composed of 741 male homosexuals with multiple sexual part-

ners.^[92] Risk factors for seropositivity (31 percent tested positive when the first serum samples were collected in 1984-1985) included the number of sexual partners with whom one was anal-receptive, and the use of recreational drugs like cannabis and nitrite.

Anal-receptive sex, after adjusting for number of sexual partners, was also identified as a risk factor for HIV infection in homosexual males in a San Francisco study;^[93] implicated as well was a history of dildo or anal-douche use. This investigation, unlike the previous two, was based on a random population sample.^[94]

The three studies cited and others now appearing suffer from distinct limitations: They are restricted to high-risk groups, homosexual men in particular, and they depend primarily on volunteers, some of whom are drawn from STD-clinic populations. It is consequently possible that the prevalence of HIV infection reported may be unrepresentatively high.^[95]

Despite these methodological problems, consistent results have obtained, raising the possibility of behavioral-intervention strategies. Specifically, probability of HIV infection varies in homosexual / bisexual men with the number of sexual partners with whom specific acts are performed. In particular, those who engage in anal-receptive sex are at greater risk of infection than those involved in other sexual behavior, including masturbation and oral-genital or insertive-anal sex.^[96] In the population studied, HIV infection is an STD in which anal mucosa, traumatized by frequent contact or douching, appears to be an inefficient barrier to infection.^[97] How drugs are associated with infection, if at all, remains conjectural.

When epidemiologists have researched the natural history of HIV-associated disorders in infected persons, they have provided information on incidence and prevalence rates and, in the main, on biological markers and disease status. Their attempts to isolate cofactors for AIDS has yielded little solid data. In addition, these investigations, like those discussed above, suffer from limitations. For example, most studies cannot specify the dates of HIV infection in their study subjects. Consequently, endpoint diseases (lymphadenopathy, for example, or AIDS itself) cannot be linked to and measured from a precisely defined date of HIV infection. This lacuna often prevents researchers from determining if a statistically significant variable is actually a surrogate for duration of infection; it also inhibits comparisons of findings across studies and the prediction of time-measured outcomes.

One of the first epidemiologic studies of the course of HIV infection was that of Harold Jaffe and his colleagues, which followed a cohort of

6,875 male homosexuals and bisexuals recruited originally between 1978 and 1980 from STD patients at San Francisco City Clinic.^[98] The researchers found that by 1984, 87.4 percent of a putative random sample^[99] of the cohort were seropositive, compared to 4.5 percent in 1978, and that 28.9 percent of the sample either had AIDS or a related condition. For each case of AIDS, 7.5 men had generalized lymphadenopathy, 1.1 had other prodromal signs of the syndrome, and 0.8 had blood-related abnormalities.

Similarly distressing results were obtained in a 1984 study of the long-term effects of HIV seropositivity in a cohort of 134 Danish men, a segment of a larger group of male homosexuals followed since 1981.^[100] Two of the twenty-two initially healthy, albeit seropositive, men developed AIDS, and 92 percent of those seropositive for more than twenty-nine months developed a T-cell count indicative of immunological defects. Although the authors did not know if those defects were predictive of AIDS, they cited unpublished data that supported the possibility.

The study of B. Frank Polk and his colleagues, unlike the previous two studies, attempted to define predictors of AIDS in seropositive men by studying a cohort of 1,835 male homosexual volunteers recruited by centers in four cities, Los Angeles, Chicago, Pittsburgh, and Washington / Baltimore.^[101] When each of the fifty-nine AIDS cases (developing over a median time of fifteen months) were matched to five seropositive controls from the same study center, the researchers found that a decreased number of T helper cells, a low level of HIV antibody, increased titers (concentration of antibodies) to CMV, and a history of sex with someone who subsequently developed AIDS were each independent predictors of the syndrome. The first three predictors, however, are probably biological markers of disease progression to AIDS rather than determinants or causes of that progression.^[102] Perhaps useful for diagnostic purposes, they offer little in the way of intervention or prevention. The last predictor—history of sex with someone who subsequently developed AIDS—may in fact be a marker of an infection long-standing enough for AIDS to develop in both partners.

Polk's investigation is limited in that it cannot specify the date of seroconversion in cases and controls. An exception to this study and others is one by Goedert and his colleagues, who followed a cohort of hemophiliacs with documented dates of seroconversion.^[103] The results derived from this study suggest that, in adults, AIDS usually appears more than two years after the initial infection, with new cases continuing to develop more than five years later.^[104]

Why does AIDS have such a variable incubation period? This fact intrigues researchers, and suggests the possibility of cofactors—exogenous or endogenous exposures that might modulate the rate of HIV-induced immunodeficiency.^[105] Some have suspected that a history of microbial infections, leading to immunological alterations, may put individuals at greater risk of infection and of disease progression.^[106] Others have suggested genetic factors, a hypothesis bolstered by a recent report that inheritance of one form of a protein (group-specific component) appears to protect against HIV, whereas inheritance of another form of the protein leaves individuals susceptible.^[107] There are also epidemiologic indications that age-related variables may be important, because infants and older homosexual men have higher rates of disease progression than other groups;^[108] pregnancy may also increase the rate of AIDS, pointing to hormones as possible cofactors.^[109]

The possible role of cofactors testifies to the terrible complexity of HIV infection and justifies the reluctance of epidemiologists to reduce AIDS and related conditions to an agent-host phenomenon. Epidemiologic researchers have consistently held up the possibility of nonviral factors to the "bench" scientists. Since 1981 they have rooted biological or clinical events in the matrices of human behavior and social experience. In a 1987 study on the role of cofactors in HIV infection, the authors put the epidemiologists' position quite well.^[110] Citing the viral etiology common to all patients with AIDS, they stressed the multiple determinants probably responsible for HIV infection and disease progression, including cultural differences, the presence of other endemic illnesses, and host and viral genetic factors. Their position reaffirms the multifactorial model as central to an understanding of HIV infection and to its control.

In 1988, with no vaccine available and only one drug approved for treating AIDS in the United States, the most effective intervention is that of primary prevention—that is, the elimination or reduction of behavior that increases risk of HIV infection. Epidemiology has traditionally been associated with primary prevention—for example, in the nineteenth-century campaigns for clean water and the proper disposal of waste and sewage, and more recently in the elucidation of the link between chronic diseases and "life-style" factors, such as diet or exercise. The multifactorial model itself, with its genealogic web of causes, assumes interdiction points that ideally occur prior to infection or the onset of disease.

Epidemiologists and their collaborators have already gathered the in-

formation needed in order to implement programs of primary prevention. Such programs recommend limiting the number of sexual partners taken and the types of sexual acts engaged in, an end to sharing needles or syringes, and counseling infected women about the consequences of pregnancy.^[111] Epidemiologists must now evaluate the efficacy of these programs, a task they have already begun in a rather limited fashion.^[112]

Can a massive campaign of public health education alter intimate habits, physical addictions, or the desire of women infected with the HIV to be mothers? Unequivocal answers are impossible: One major problem is that programs to modify high-risk behavior will inevitably run up against socially powerful attitudes toward "deviance" that may require wrenching public-policy choices. Another important issue is the paucity of scientific knowledge regarding human sexual behavior, limiting the effectiveness of educational programs. Here epidemiology can be of some assistance. Having raised the "life-style" issue originally, having maintained the importance of social experience and behavior in the scientific understanding of disease processes, epidemiology can commit itself to studying such issues that, long taboo, have now been "normalized" by the epidemiologic approach to the HIV epidemic.

Conclusion

In this chapter I have tried to show how epidemiologists, drawing on the unique perspectives of their profession, reacted to the outbreak of a new disease of unknown cause. These scientists constructed explanations for the syndrome with equivocal results. Almost from the beginning of the epidemic, epidemiologists conceptualized HIV infection as a complex social phenomenon, with dimensions that derived from the social relations, behavioral patterns, and experiences of the population at risk. On the one hand, the epidemiologists' approach may have skewed the choice of models and the hypotheses pursued and may have offered some justification for homophobia. On the other, by defining HIV infection as a multifactorial phenomenon, with both behavioral and microbial determinants, epidemiologists offered the possibility of primary prevention, a traditional epidemiological response to infectious and chronic diseases. Epidemiologists, in effect, laid the basis for an effective public health campaign, and, through publications and conferences, helped make AIDS a concern of policymakers and the public.

Primary prevention, including blood screening, health education, and behavior modification, is currently the only effective social response to

the spread of HIV infection. Recent evidence from San Francisco indicates that the rate of HIV infection has begun to decline, possibly because of a reduction in high-risk sexual activities among homosexual males.^[113] Another investigation shows major changes in the sexual behavior of gay males in New York City.^[114] These results—hopeful signs—have not yet been linked to a decrease in HIV-associated mortality. They may presage, however, a parallel between HIV and infectious-disease history.

Historical epidemiology has shown that medical interventions, both chemotherapeutic and prophylactic, have had little impact on the overall decline in infectious-disease mortality in this century. For example, John and Sonja McKinlay found that since 1900 new medical measures have had almost no detectable effect on U.S. disease-specific mortality rates, as such measures usually occurred some decades after significant declines in death rates had already set in.^[115] Thomas McKeown and his colleagues have obtained similar results in a study on the mortality trends of England and Wales. According to McKeown, the observed secular decline was mainly attributable to community factors, particularly better nutrition and hygiene.^[116] It remains to be seen whether HIV-related mortality will also decline as a result of community-directed hygiene (condoms, clean needles, blood screening) before a vaccine or new chemotherapy can be introduced. If it does, the history of HIV infection will offer a powerful vindication of the epidemiologists' multifactorial social definition of disease and of the public health actions that followed from it.

Notes

This chapter is a considerably revised version of a paper first presented at the annual meeting of the American Historical Association in December 1986. It has been much improved by the generous comments of Ronald Bayer, Benjamin Brody, Don C. Des Jarlais, Elizabeth Fee, Daniel M. Fox, Robert Padgug, Zena Stein, Anne Stone, and Mervyn Susser.