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


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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


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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


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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-


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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


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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]


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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-


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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.


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