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Stanford BIO 230 - Study Notes

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Special Article 1764 · N Engl J Med, Vol. 344, No. 23 · June 7, 2001 · www.nejm.org The New England Journal of Medicine AIDS — THE FIRST 20 YEARS K ENT A. S EPKOWITZ , M.D. HE disease now known as the acquired immu-nodeficiency syndrome, or AIDS, was first re-ported 20 years ago this week in the Morbid-ity and Mortality Weekly Report under the quiet title“ Pneumocystis pneumonia — Los Angeles.” 1 The de-scription was not the lead article; that distinction wentto a report of dengue infections in vacationers return-ing to the United States from the Caribbean.Not even the most pessimistic reader could haveanticipated the scope and scale the epidemic would as-sume two decades later. By December 2000, 21.8 mil-lion people worldwide had died of the disease, includ-ing more Americans (438,795) than died in WorldWar I and World War II combined. 2 This article re-views the many important developments in the first20 years of AIDS. EARLY YEARS: FREE FALL The initial report described five young homosex-ual men in whom a rare disease, Pneumocystis carinii pneumonia, and other unusual infections had devel-oped. Each had abnormal ratios of lymphocyte sub-groups and was actively shedding cytomegalovirus.This report was followed quickly by more series, andwithin a few months, the basic outline of the epidem-ic was established (Table 1). Although the disease wasfirst encountered in homosexual men and injection-drug users, the risk groups soon included Haitians, 5 transfusion recipients, including those with hemo-philia, 6,10 infants, 11 female sexual contacts of infectedmen, 8,12 prisoners, 13 and Africans. 15 Additional opportunistic complications were soondescribed, including mycobacterial infections, toxo-plasmosis, invasive fungal infections, Kaposi’s sarcoma,and non-Hodgkin’s lymphoma. The working defini-tion for AIDS, developed by the Centers for DiseaseControl, 21 has required just a single revision in thepast decade. 22 Causation In the early years, there were numerous theories re-garding the cause of AIDS, many of which now seemeccentric. The evidence that the disease was caused bycytomegalovirus, as posited in the early reports, 1,23 wasstraightforward: groups with the new immunodefi-ciency had extremely high rates of infection with cy-tomegalovirus, a potentially immunosuppressive virus.T Some hypothesized that the virus had inexplicably be-come more virulent. Yet this theory failed to accountfor all cases, and attention turned elsewhere.A case was made for attributing causality to amylnitrite, a prescription drug, and to isobutyl nitrite, aclosely related chemical marketed as a room deodor-izer. 24 Both were used as sexual stimulants but werealso known immunosuppressive agents. This theoryhad scientific plausibility and suggested a simple solu-tion. But soon cases were reported among nonusers.A sophisticated theory developed around the notionthat repeated exposure to another’s sperm could trig-ger an immune response, resulting in a condition re-sembling chronic graft-versus-host disease and, ulti-mately, opportunistic infections. 25 Another hypothesisinvoked a general overloading of the immune system— a sort of physiological battle fatigue in which theimmune system simply wore out. 26,27 Outside the sci-entific community, there were suggestions that thedisease was a punishment for homosexual men andinjection-drug users. 28 A novel viral cause of the disease was only one ofmany plausible theories in the early years. It was fa-vored by those familiar with the epidemiology ofhepatitis B infection, 8,29,30 which affected the samegroups, and by those who worked with animal retro-viruses. Feline leukemia virus had been described inthe 1970s as a cause of general immunodeficiency (the“fading-kitten syndrome”) and was associated withlymphoma and leukemia as well. 31,32 For the research-ers in this field, the notion that a human retrovirusmight cause a similar syndrome was a simple intellec-tual leap.Nonetheless, doubt about a viral cause persisted un-til the actual virus was detected, 16 confirmatory stud-ies were performed, 18 and the reports of transmissionthrough blood and blood products became too nu-merous to ignore. 6,9 The complicated and rivalrous sto-ry that culminated in the isolation of the virus has beenwell described. High-stakes scientific inquiry has sel-dom been placed in a less attractive light. From the Clinical Infectious Disease Service, Department of Medicine,Memorial Sloan-Kettering Cancer Center, New York. Address reprint re-quests to Dr. Sepkowitz at the Clinical Infectious Disease Service, Memo-rial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021,or at [email protected] from www.nejm.org at Stanford University on September 29, 2003.Copyright © 2001 Massachusetts Medical Society. All rights reserved.AIDS — THE FIRST 20 YEARS N Engl J Med, Vol. 344, No. 23 · June 7, 2001 · www.nejm.org · 1765 The delay on the part of some in accepting a novelviral cause may appear puzzling now, but investiga-tors may have been intimidated by the enormous im-plications that a new virus would carry for blood bank-ing, the safety of health care workers, and the overallpublic health. There was also a hesitancy, particularlyamong those outside the medical community, to ac-knowledge that the infection could be spread throughheterosexual contact. Indeed, many preferred to invokeany but the obvious cause. The spread of the diseasein Haiti, for example, was postulated to be a result ofvoodoo practices rather than heterosexual sex. 33 To-day, most human immunodeficiency virus (HIV) in-fections in the world derive from heterosexual trans-mission — a fact that is still overlooked by many.In some quarters, doubt persists that HIV causesAIDS. One prominent dissident has theorized thatthe disease occurs because of long-term use of recre-ational drugs and is exacerbated by nucleoside ana-logues given as treatment. 34 The improvements thathave been made in antiviral therapies for HIV diseasehave, paradoxically, only intensified the debate. 35,36 Treatment Recent advances in therapy have obscured the dif-ficult and often demoralizing character of the early *CDC denotes Centers for Disease Control, FDA Food and Drug Administration, HIV human immunodeficiency vi-rus, HTLV human T-cell lymphotropic virus, and NIH National Institutes of Health.†Each quoted statement is from the


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