Except in Africa, where HIV and AIDS appear virtuallyendemic, the affliction is blamed by and large on two"lifestyles" _ homosexuality and drug abuse. But yearsbefore the human immunodeficiency virus was suspected,let alone discovered and named, a third population hadacquired the infection by stealth.

These were the victims of hemophilia, a hereditary blood-deficiency disease, in which lack of clotting factorscauses death by uncontrolled bleeding. Only massive andfrequent transfusions of donor blood, or concentratedcoagulation factors, could keep severely-affectedhemophiliacs alive.

More than a decade ago, this heroic blood-replacementregimen began proving more deadly than the disease ittreated. AIDS and cancer epidemiologist James Goederttold BioWorld Today why:

"In hemophilia you had two situations: First: A veryefficient vehicle _ plasma concentrated from the bloodof several thousand donors _ for transmitting the virus.Second: A highly susceptible population that needed a lotof the stuff. As a consequence, the epidemic reallyoccurred in a burst, and nearly all of the susceptiblehemophiliacs were infected before anybody could doanything about it."

Transfusion-Borne HIV Infected Half Of Recipients

Biostatistician Philip Rosenberg of the National CancerInstitute (NCI), in Washington, said that by July 1985,when screening and heat treatment ended the HIVcontamination, 6,800 of the 13,000 adult hemophiliacs inthis country tested positive for HIV.

These numbers are visibly round. But the Sept. 7, 1995,issue of Nature presents a report that its first author,statistical epidemiologist Sarah Darby, described toBioWorld Today as "perhaps the only example in theworld where you have mortality data on a completepopulation."

Darby is a staff scientist with the Imperial CancerResearch Fund at Oxford University in England. HerNature paper bears the title: "Mortality before and afterHIV infection in the U.K. population of haemophiliacs."Its stark statistics tell the story's main outlines:

* Between 1977 and 1991, 6,278 people diagnosed withhemophilia were living in the U.K. "Some of thosepeople," Darby observed, "were infected completely atrandom with HIV. As all severe hemophiliacs arecompletely dependent on transfusion therapy," she added,"it was literally a matter of luck whether these people gotinfected or not. It had nothing to do with their lifestyle."

* By 1986, 1,227 of them were seropositive for HIV-1.

* Of the 6,278 total, 2,448 cases were "severe," requiringmany transfusions.

* The remaining 3,830 were "mild or moderate."

* Between 1977 and 1984, the overall death rate in thehemophiliac population amounted to eight per 1,000. Inthe following seven years, that ratio held good forpatients found seronegative for the virus. Among theseropositive, it was tenfold greater _ 81 deaths per1,000.

* Overall, AIDS deaths among Britain's hemophiliacsreached 403 by 1992.

Of what did they die? "We've got only limitedinformation as to the cause of death," Darby said, "onlytwo facts: Whether or not they were diagnosed withAIDS. And what's written on their death certificates.

"The things they died of," she continued, "were prettytypical of HIV-related opportunistic infections, such aspneumocystic pneumonia. But we know, partly from thisstudy, and partly from others, that hemophiliacs are veryunlikely to get Kaposi's sarcoma [KS]."

Goedert, who is acting chief of viral epidemiology at theNCI, told BioWorld Today: "KS was one of the originalAIDS-defining diseases, found preponderantly amonghomosexual men. It's long been known that KS rarelyoccurs in people with hemophilia. We're aware of only24 in the U.S., a low number compared with thethousands of cases."

He added, "Columbia University researchers wereintrigued by the possibility that a sexually transmittedagent causes KS, not HIV. Using a polymerase chainreaction subtraction technique called representationaldifference analysis, they compared DNA sequences in KStissue to normal skin in the same person. What they foundwas DNA that appears to represent the discovery of a newhuman herpes virus, HHV8, in the KS tissue."

From this finding, Goedert continued, "The absence ordeficiency of KS in persons with hemophilia suggests thatif there is such a virus, it is highly cell-associated, anddoes not, or rather did not, readily circulate in plasma, sodidn't get into Factor VIII concentrates. It remains to beproven whether this putative virus contributes to thecause of KS."

Another conclusion from Darby's study, which she finds"depressing," is that the risk of mortality increasedsteadily every year. "Actually," she observed, "it meansthat the increasing risk hasn't been halted by thetreatments that were available up to 1992."

It's Goedert's opinion that "You can't judge efficacy oftherapy from this statistical data, because what you'retrying to do is compare it with a situation in which therewere no therapies. Mortality might have been higher."

Killed By A Virus Then Unknown

Darby cited another take-home message from the Britishsurvey "that is not exactly something we know now butdidn't know before." She explained: "When thesuggestions are made _ and they are repeatedly madefrom various different corners _ that HIV isn't really acausative virus, but a passenger virus, we'll be able tosay: `Well, look, if that were the case then these datawouldn't exist. They really do demonstrate that HIV cancause AIDS. HIV can cause death.'"

To which Goedert said: "If I were the author of thispaper, I wouldn't try to make that claim from thisdescriptive epidemiology data. I think there are betterexamples, such as case reports of health care workerswith a needle-stick injury, who get AIDS and die."

He concluded, "One thing I picked up from the Darbypaper that corroborates our work is that the vast majorityof infections in persons with hemophilia occurred beforethe disease was recognized. There wasn't anything thatanybody could have done about it, because no one knewit existed." n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.

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