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The Ne w E n g l a nd Jo u r n a l o f Me d ic i ne

Special Article

AIDS — THE FIRST 20 YEARS
KENT A. SEPKOWITZ, M.D.

T

HE disease now known as the acquired immunodeficiency syndrome, or AIDS, was first reported 20 years ago this week in the Morbidity and Mortality Weekly Report under the quiet title “Pneumocystis pneumonia — Los Angeles.”1 The description was not the lead article;that distinction went to a report of dengue infections in vacationers returning to the United States from the Caribbean. Not even the most pessimistic reader could have anticipated the scope and scale the epidemic would assume two decades later. By December 2000, 21.8 million people worldwide had died of the disease, including more Americans (438,795) than died in World War I and World War IIcombined.2 This article reviews the many important developments in the first 20 years of AIDS.
EARLY YEARS: FREE FALL

The initial report described five young homosexual men in whom a rare disease, Pneumocystis carinii pneumonia, and other unusual infections had developed. Each had abnormal ratios of lymphocyte subgroups and was actively shedding cytomegalovirus. This report was followed quickly bymore series, and within a few months, the basic outline of the epidemic was established (Table 1). Although the disease was first encountered in homosexual men and injectiondrug users, the risk groups soon included Haitians,5 transfusion recipients, including those with hemophilia,6,10 infants,11 female sexual contacts of infected men,8,12 prisoners,13 and Africans.15 Additional opportunisticcomplications were soon described, including mycobacterial infections, toxoplasmosis, invasive fungal infections, Kaposi’s sarcoma, and non-Hodgkin’s lymphoma. The working definition for AIDS, developed by the Centers for Disease Control,21 has required just a single revision in the past decade.22
Causation

In the early years, there were numerous theories regarding the cause of AIDS, many of whichnow seem eccentric. The evidence that the disease was caused by cytomegalovirus, as posited in the early reports,1,23 was straightforward: groups with the new immunodeficiency had extremely high rates of infection with cytomegalovirus, a potentially immunosuppressive virus.

Some hypothesized that the virus had inexplicably become more virulent. Yet this theory failed to account for all cases,and attention turned elsewhere. A case was made for attributing causality to amyl nitrite, a prescription drug, and to isobutyl nitrite, a closely related chemical marketed as a room deodorizer.24 Both were used as sexual stimulants but were also known immunosuppressive agents. This theory had scientific plausibility and suggested a simple solution. But soon cases were reported among nonusers. Asophisticated theory developed around the notion that repeated exposure to another’s sperm could trigger an immune response, resulting in a condition resembling chronic graft-versus-host disease and, ultimately, opportunistic infections.25 Another hypothesis invoked a general overloading of the immune system — a sort of physiological battle fatigue in which the immune system simply wore out.26,27Outside the scientific community, there were suggestions that the disease was a punishment for homosexual men and injection-drug users.28 A novel viral cause of the disease was only one of many plausible theories in the early years. It was favored by those familiar with the epidemiology of hepatitis B infection,8,29,30 which affected the same groups, and by those who worked with animalretroviruses. Feline leukemia virus had been described in the 1970s as a cause of general immunodeficiency (the “fading-kitten syndrome”) and was associated with lymphoma and leukemia as well.31,32 For the researchers in this field, the notion that a human retrovirus might cause a similar syndrome was a simple intellectual leap. Nonetheless, doubt about a viral cause persisted until the actual virus was...
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