OCCASIONAL PAPERS DECEMBER 2007 • NO 6 THE TRAGIC HISTORY OF AIDS IN THE HEMOPHILIA POPULATION, 1982–1984 B.L. Evatt Centers for Disease Control Atlanta, GA, U.S.A. This document was originally published by Blackwell Publishing in Journal of Thrombosis and Haemostasis, vol. 4, issue 11: pp 2295-2301, 2006. It is reprinted with permission. This publication is accessible from the World Federation of Hemophilia’s web site at www.wfh.org. Additional copies are also available from the WFH at: World Federation of Hemophilia 1425 René Lévesque Boulevard West, Suite 1010 Montréal, Québec H3G 1T7 CANADA Tel. : (514) 875-7944 Fax : (514) 875-8916 E-mail: [email protected] Internet: www.wfh.org The Occasional Papers series is intended to provide a forum for examining a wide range of topics of interest to the hemophilia community. The World Federation of Hemophilia does not engage in the practice of medicine and under no circumstances recommends particular treatment for specific individuals. Dose schedules and other treatment regimes are continually revised and new side effects recognized. WFH makes no representation, express or implied, that drug doses or other treatment recommendations in this publication are correct. For these reasons it is strongly recommended that individuals seek the advice of a medical adviser and/or to consult printed instructions provided by the pharmaceutical company before administering any of the drugs referred to in this monograph. Statements and opinions expressed here do not necessarily represent the opinions, policies, or recommendations of the World Federation of Hemophilia, its Executive Committee, or its staff. Journal of Thrombosis and Haemostasis, 4: 2295–2301 HISTORICAL SKETCH The tragic history of AIDS in the hemophilia population, 1982– 1984 B. L. EVATT Vice President Programs, World Federation of Hemophilia, and Director (Retired), Division of Hematology, Centers for Disease Control, Atlanta, GA, USA To cite this article: Evatt BL. The tragic history of AIDS in the hemophilia population, 1982–1984. J Thromb Haemost 2006; 4: 2295–301. Consequently, plasma demand rose significantly, and the need for volume rather than quality drove the plasma industry. Introduction: building the paradigm of hemophilia care Plasma was often obtained from paid donors who had high risks of blood-borne diseases (those who were extremely poor, During the first four decades of the 20th century, life for prisoners, alcoholics, etc.) [2]. As a result, clotting factor patients with hemophilia was at best miserable. Usually concentrates, derived from pools of up to 20 000 donors with disabled before the age of 20, life expectancy for these patients inadequate donor screening and infective agent testing, almost averaged 27 years because of early deaths, often from bleeding uniformly infected patients with hepatitis [12–13]. Considering into vital organs [1]. Because of the improvements in transfu- the enhanced quality of life and increased longevity, these high sion technology made during World War II [2–3], hemophilic infectivity rates were deemed an acceptable risk by patients, patients could receive infusions of fresh whole blood or fresh physicians, industry and government; viral inactivation tech- frozen plasma containing the missing clotting factor. As a nology was not vigorously pursued. result, the life expectancy for a severe hemophilic patient reached 39.7 years by 1960, but the crippling effects of repeated bleeds left a substantial proportion of the population The epidemic begins disabled and unemployed. Development of cryoprecipitate and It was in this setting that a new blood-borne disease, acquired subsequent fractionation procedures in the 1960s allowed immune deficiency syndrome (AIDS), was spawned in Africa storage of a therapeutic form of clotting factor VIII (FVIII), and transmitted by social and sexual intercourse of populations the missing clotting factor in hemophilia A [4–6]. Commercial at high risk for blood-borne disease into the Caribbean, the adaptation yielded lyophilized clotting factor concentrates that USA and other countries of the developed world. immediately raised the missing clotting factor to normal levels, First apparent in the homosexual population in the USA could be carried with patients on trips and could be self- in the last quarter of 1980, the disease possessed unusual administered. properties that initially obscured it as a distinct infectious Both patients and physicians regarded clotting factor disease. Previously healthy victims had no specific symptoms concentrates as the ultimate solution to hemophilia. Home but presented with either secondary infections or tumors care programs grew and comprehensive hemophilia treatment associated with immune deficiency [i.e. Pneumocystis carinii centres (HTC) developed [7–9]. Patients attending HTCs pneumonia (PCP) or Kaposi’s sarcoma] [14,15]. A long experienced substantial improvement of medical care and incubation time made it difficult to identify person-to-person better quality of life as dependency on the medical community spread. Laboratory methods needed to culture and identify decreased. Mortality rates fell dramatically, employment levels the etiologic agent were lacking. Leading scientists focused increased, and school and work absences diminished greatly as on non-infectious causes, such as antibodies to sperm or hospitalizations and complications of hemophilia decreased reaction of the immune system to chemicals such as inhaled [10–11]. Life expectancy reached 60 by 1980, nearly that of amyl nitrites that homosexuals used to maintain prolonged normal males. erections [16,17]. The course of the investigation began to change in 1982. The Centers for Disease Control (CDC), the federal agency Correspondence: Bruce L. Evatt, Vice President Programs, World responsible for investigating new infectious diseases, had just Federation of Hemophilia, and Director (Retired), Division of experienced a major reorganization and severe budgetary and Hematology, Centers for Disease Control, Atlanta, GE, USA. staff reductions. The author directed the Division of Host Tel.: +1 404 634 1030; fax: +1 404 634 1030; e-mail: ble2@ Factors, which was responsible for investigation of new mindspring.com drugs, one of which was pentamidine, the drug used to treat Ó 2006 International Society on Thrombosis and Haemostasis 2296 B. L. Evatt the PCP common in AIDS patients. Epidemiologists at the Investigation confirmed the presence of the immune disorder. CDC were already investigating the new disorder in homo- We were now reasonably convinced that hemophilic patients sexual men. were another risk group for AIDS. The author notified Dr In early 1982, the author received a call reporting a William Foege, Director of the CDC, and drafted a letter for hemophilic patient who, treated with FVIII concentrates, had him to warn all the HTC directors. The Executive Director of died of PCP. The physician reasoned that the clotting factor the National Hemophilia Foundation (NHF) was notified of was contaminated with P. carinii and was transmitted directly the implications and NHF’s cooperation was enlisted to to the patient. However, the manufacturing process would have provide support for further surveillance and investigations. removed contaminating P. carinii, and the rarity of PCP in The CDC published a Morbidity and Mortality Weekly Report hemophilia suggested the possibility that the patient had (MMWR) article reporting the three patients and suggesting acquired the same syndrome that was affecting homosexuals. the probability of a blood-borne infection as a cause of AIDS After investigating, the author determined that the patient’s [18]. clinical record was consistent with the new disorder, but the In July 1982, we reasoned that the time had come to shift US patient’s death precluded confirmatory tests. investigations towards a blood-borne and sexually transmitted Almost simultaneously, the CDC received reports of a infection as a cause of AIDS [19]. The members of the blood similar immune disorder in Haitian patients and i.v. drug banking and plasma industry, the affected patient groups, the abusers. As anal intercourse or use of amyl nitrites, prevailing hematology professional organizations and government agen- theories regarding the cause of the homosexual disease, were cies needed to be briefed and an attempt made to reach a not common practices for hemophilic patients, Haitians or i.v. consensus position, and ideally, to concur on preventive action, drug abusers, the author reasoned that these four groups had such as blood donor deferral guidelines directed toward very little in common except for one thing, a risk for blood- excluding high-risk groups from donating blood. borne diseases (Table 1). However, these actions could not be easily achieved. My division began to vigorously pursue the possibility that Although the implications of finding the syndrome in the four the new syndrome was blood borne. The author requested a risk groups provided a strong suggestion of a possible blood- review of the pentamidine request files, in search of other borne disease, no direct proof existed that showed the hemophilic patients with PCP. None had ever been received. A syndrome was infectious or transmitted by blood. No agent thorough search of scientific journals identified only one had been found and no tests existed to screen potentially hemophilic patient who had developed PCP following high- infected persons. dose ACTH injections a decade earlier. Calls to Dr David Aronson