SPECIAL NEWS REPORT 1 REVIEWING THE DATA–I the Multicenter Hemophilia Cohort Study 66 2 (MHCS) sponsored by the National Cancer 65 3 Institute (NCI), follows 2000 hemophiliacs 64 4 Duesberg and Critics Agree: at 16 centers in the United States and West- 63 5 ern Europe. In 1989, the New England Journal 62 6 Hemophilia Is the Best Test of Medicine published a study from the 61 7 MHCS comparing 242 HIV-infected hemo- 60 8 philiacs who received high, medium, or low 59 9 Peter Duesberg and his critics in the com- addition, some researchers contacted by Sci- doses of factor VIII. If exposure to contami- 58 10 munity of AIDS researchers disagree vio- ence say Duesberg has drawn incorrect con- nants in factor VIII were the cause of the 57 11 lently about the cause of AIDS. But they clusions from their work. immune suppression seen in AIDS, it would 56 12 agree on one thing: Hemophiliacs provide a In making his argument that hemophili- be expected that those who received higher 55 13 good test of the hypothesis that HIV causes acs suffer from AIDS independent of HIV, doses of the factor would be more likely to 54 14 AIDS. Hemophiliacs offer a unique window Duesberg cites 16 studies showing that HIV- develop AIDS, says NCI’s James Goedert, 53 15 on the effects of HIV infection because there negative hemophiliacs have abnormal ratios the principal investigator of MHCS. But the 52 16 are solid data comparing those who have of two types of critical immune-system cells: study, says Goedert, found no association 51 17 tested positive for antibodies to HIV—and CD4 and CD8. The normal ratio of CD4s to between dose levels and the likelihood of 50 18 are presumably infected—with those who CD8s is about 2, but the studies Duesberg coming down with AIDS. 49 19 have tested negative. In addition, the health cites indicate that hemophiliacs who are not Duesberg, however, thinks studies such as 48 20 status of hemophiliacs has been tracked for HIV-positive have ratios closer to 1. He con- 47 21 more than a century, providing an important cludes that even in the absence of HIV, he- DEATHS IN HEMOPHILIA /NCI 46 22 base line. And unlike homosexual groups, mophiliacs suffer immune deficiencies—and COHORT SINCE 1985* 45 23 hemophiliac cohorts are not riddled with hence that some factor other than HIV is 44 24 what Duesberg thinks are confounding vari- responsible for AIDS among them. Factor VIII Dose HIV+ HIV– 43 High 10/29 0/0 25 ables, such as illicit drug use. But researchers familiar with these data JAMES GOEDERT 42 26 Where AIDS researchers argue that HIV say the abnormal ratio Duesberg cites is not Moderate 103/264 0/17 41 27 causes AIDS in hemophiliacs, Duesberg indicative of AIDS—and may not even indi- Low 40/103 1/49 40 28 points to another cause: contaminants of fac- cate immune deficiency. The chief impact of *Groups are based on cumulative dosages of factor 39 29 tor VIII, a clotting factor derived from do- AIDS on the immune system is a progressive VIII from 1978 to 1984. 38 30 nated blood that is used to treat hemophilia. decline in the number of CD4 cells. A 37 31 Factor VIII is frequently contaminated with change in the CD4/CD8 ratio doesn’t in it- MHCS aren’t sufficient for establishing 36 32 foreign proteins from blood donors, and self say anything about the number of CD4 AIDS causality. He says more research is 35 33 Duesberg suggests that these contaminants cells, AIDS researchers say, as it could be due needed—specifically, a study that doesn’t 34 34 cause the immunodeficiency seen in AIDS. to an elevation of CD8 cells alone. “Any- combine hemophiliacs into groups such as 33 35 In his view, HIV is a harmless passenger that thing that would give your CD8s an eleva- “high, medium, and low dosage” and that 32 36 serves as an index of the number of blood tion could give you a ratio of 1,” says immu- instead includes records of exactly how much 31 37 transfusions. “Since HIV is a rare contami- nologist Michael Ascher, an AIDS re- factor VIII each patient has received during 30 38 nant of factor VIII, it is a marker of the num- searcher with the California Department of his or her lifetime. “We would need a study 29 39 ber of immunosuppressive transfusions re- Health Services. People with a ratio of 1 comparing 100 hemophiliacs—and it’s very 28 40 “could have more CD4s—and that may be doable; it’s probably in the computer—hav- 27 1.50 41 70 Median Age at Death immuno wonderful,” adds Ascher. ing received 2 million lifetime units [of factor 26 42 1.25 60 When asked about this point in relation VIII] to 100 guys having received exactly the 25 43 to a specific paper he cites, Duesberg re- same number of units, HIV positive and 24 50 44 1.00 sponded: “Look, why don’t you call [the negative. And then compare [the diseases in 23 40 45 0.75 paper’s author] and ask the fool, ‘Why did each group]. Not this type of stuff.” 22 46 30 you idiots describe your paper as immunode- In spite of Duesberg’s contention that 21 0.50 47 20 ficiency in patients with hemophilia?’ ” such a study is “very doable,” researchers 20 48 Deaths per million 0.25 Pediatrician Donald Kaufman of Michi- working with hemophilia databases say it is 19 SOURCE: TERENCE CHORBA/CDC 10 49 gan State University, who co-authored the impossible, because hemophiliacs do not 18 0.00 0 50 ’68 ’70 ’72 ’74 ’76 ’78 ’80 ’82 ’84 ’86 ’88 study in question, says Duesberg’s interpreta- keep track of each factor VIII treatment. 17 51 Year tion of their data is “erroneous.” In Kauf- “There’s no place that would even begin to 16 52 Crossing pattern. Death rates for hemophili- man’s 1989 study, CD4 counts of HIV-nega- have cumulative lifetime dosages,” says the 15 53 acs rose sharply in the 1980s. AIDS research- tive hemophiliacs showed no significant dif- University of Southern California’s James 14 54 ers disagree with Duesberg on the cause. ference from normal controls. The number Mosley, who heads the other large study of 13 55 of CD8 cells, however, was higher in hemo- hemophiliacs, the Transfusion Safety Study 12 56 ceived,” argues Duesberg. He contends that philiacs—regardless of whether they re- Group (TSSG), which has tracked 1200 he- 11 57 hemophiliacs infected with HIV are simply ceived factor VIII treatment. The treated pa- mophiliacs at six U.S. sites. “It’s sort of like 10 58 the ones who have received the most factor tients did show some immune deficiencies that trying to count grains of sand on the beach.” 9 59 VIII—with the accompanying contaminants. Kaufman thinks may be related to factor VIII, Although Mosley and others say precise 8 60 AIDS researchers interviewed by Science but he emphasizes that these were nothing lifetime dosages of factor VIII for large study 7 61 contend that this view is contradicted by two like what is seen in AIDS, and indeed, none groups are impossible to obtain, they say it is 6 62 large studies of hemophiliacs. Those studies, of these nine patients has developed AIDS. possible to do less ambitious studies that look 5 63 say AIDS researchers, show that being HIV Other AIDS researchers cite additional at cumulative dosages of factor VIII for spe- 4 64 positive is the key variable associated with data from the two large epidemiologic studies cific periods, such as when hemophiliacs are 3 65 the disease and death that accompany that they argue show factor VIII has little to being monitored in a study. NCI’s Goedert 2 66 AIDS—not contaminants of factor VIII. In do with causing AIDS. One of these studies, did such an analysis using his MHCS data- 1 SCIENCE • VOL. 266 • 9 DECEMBER 1994 1645 1 165, or 31%, of the 519 HIV-positive hemo- 66 2 philiacs had developed AIDS. In the HIV- 65 3 The Transfusion Studies positive group there were 176 deaths, and of 64 4 those, 135 were from AIDS. 63 5 Although science has produced no AIDS cure or vaccine, AIDS researchers like to For many “HIV dissenters,” Duesberg’s 62 6 point to one dramatic victory: the blood test that prevents people from being infected most compelling argument against HIV as 61 7 during transfusions. According to the Centers for Disease Control and Prevention the cause of AIDS in hemophiliacs is his 60 8 (CDC), as of mid-1994, 6888 AIDS cases had been linked to blood transfusions. But observation that the median age of hemo- 59 9 those people were almost all infected before screening began, and the blood test has philiacs has increased in spite of high HIV 58 10 essentially eliminated the risk of AIDS from transfusions—only 29 cases stem from infection rates. As Duesberg notes, studies 57 11 blood that was screened for HIV. This dramatic decrease has been invoked by AIDS have reported that the median age of hemo- 56 12 researchers as evidence that HIV causes AIDS. philiacs in the United States has risen from 55 13 Peter Duesberg says these data are meaningless. He argues that AIDS is not caused by 11 years in 1972 to more than 25 years by the 54 14 HIV in transfused blood but by the disease that required transfusion in the first place.