COLUMN ONE : Cruel Link: Hemophilia and AIDS : Transfusions that once were seen as a salvation brought a deadly epidemic in the 1980s. After a decade of anguish and frustration, survivors are fighting back.
Josiah Andrew Alvarado is buried on a grassy slope in the Hollywood Hills, in the shadow of a stand of giant pine trees and pink-blooming oleanders. His is a simple grave, marked by a brass tablet bearing a quote from Psalms and figures befitting a child just shy of his eighth birthday: a goose and rabbit, a cherub, teddy bear and lamb.
His mother doesn’t come to the cemetery much. Visiting is too painful.
It has been five years since her only child, a hemophiliac, died of AIDS. Today, Joan Alvarado is brokenhearted, bitter and angry--at the doctors she feels betrayed her, at the manufacturer of the blood concentrate that should have saved Josiah’s life but infected him with the human immunodeficiency virus instead, and paradoxically at herself, for unknowingly administering the deadly infusion.
“I struggle with that every day of my life, even though intellectually I know it wasn’t my fault,” she said. “What makes you angry is you put your trust in these people. They did nothing but lie to me. Nobody told me death was a side effect of this concentrate. Yes, it was a wonderful product. Yes, he needed it. But they helped me murder my son.”
The death of Josiah Alvarado speaks volumes about the tragic link between AIDS and hemophilia. Through tainted blood products distributed in the early 1980s, HIV has decimated the hemophiliac population in the United States and other developed nations that imported the U.S.-made concentrate.
A decade later, the death toll is mounting. Survivors, many of whom remained silent for fear that they would be stigmatized, are now going public and fighting back.
In the United States, officials estimate that half the 20,000 hemophiliacs are HIV-positive, and the infection rate is 80% in those with severe forms of the blood-clotting disorder. By the end of 1993, the U.S. Centers for Disease Control and Prevention had documented 3,342 AIDS cases among hemophiliacs. As a result of the epidemic, the median life expectancy of a person with hemophilia declined from 57 years in 1979 to 40 in 1989.
Families are being wiped out. Wives of hemophiliacs (the disorder is genetic, passed from mother to son, and afflicts men almost exclusively) have contracted AIDS from their husbands, or passed HIV to their children.
Generations are disappearing. In San Bernardino County, a couple had four sons with hemophilia. Three are dead and the fourth is HIV-positive. AIDS has also claimed two of the wife’s hemophiliac brothers, and her nephew is infected. Said the husband: “You’re constantly worried about one and grieved about the other.”
Amid this “hemophiliac holocaust,” as some have called it, there is a growing movement to avenge the deaths through lawsuits and legislation. It has been a time-consuming and emotional campaign.
Often, it has not been successful.
In Los Angeles, lawyers for Joan Alvarado and her husband, Tim, spent five grueling weeks this summer trying to persuade a Superior Court jury that Baxter Hyland Therapeutics, one of four companies that manufactured the concentrate, was responsible for Josiah’s death by failing to take adequate precautions to keep HIV out of its products.
But the case, like so many others brought by hemophiliacs, was extremely difficult to prove, and the couple lost--as have the plaintiffs in all but one of 11 other cases that have gone to trial.
In Chicago, however, hemophiliacs recently scored a legal victory: This month, a judge ruled that there was enough evidence for a group called the Committee of Ten Thousand (COTT)--named for the 10,000 infected--to bring a class-action lawsuit against the manufacturers and, ironically, the nonprofit National Hemophilia Foundation.
The suit alleges that the foundation, like the companies, knew the blood products were risky but failed to warn its members because it received funding from the manufacturers. While the foundation has declined comment, the manufacturers have denied wrongdoing, saying the infections occurred long before anyone knew that the blood supply was unsafe and thus could not have been prevented.
“Everyone understands what a terrible tragedy this is, what a horrible disaster this has been for the community,” said Duncan Barr, attorney for Miles Inc., one of the pharmaceutical company defendants. “But the fact that something bad happened doesn’t necessarily mean that it is someone’s fault.”
Yet the Committee of Ten Thousand says fault abounds, not only with the companies, but with the federal government, for failing to protect the blood supply in the epidemic’s early days.
Already, the committee’s efforts have sparked an inquiry by the Institute of Medicine--the research arm of the National Academy of Sciences--into how the products became tainted; a hearing is set in Washington for Sept. 12. And the advocacy group is pressing Congress to make reparations to infected hemophiliacs, noting that most Western nations--including Canada, Spain, the United Kingdom and France--have done so.
Its harshest criticism, however, is reserved for the manufacturers. Two companies, Baxter Hyland and Rhone Poulenc Rorer, together have offered to pay $30,000 to each infected person--not to admit guilt but simply to settle the lawsuit. “An insult,” is how one COTT board member described the offer. When the judge ruled that the lawsuit could go forward, the settlement collapsed.
“This was 100% avoidable,” said Jonathan Wadleigh, a Massachusetts computer salesman who, angry over his own HIV infection, founded COTT in 1990. “I’m a business person, and I understand sales. But I also understand the value of human life and ethics. These companies put their profit before human lives. They should be held accountable for what they did, and we intend to hold them accountable.”
No lawsuit, of course, will bring back Josiah Alvarado.
Nor has the legal system done much to ease the pain of his parents, who have forced themselves to relive the details of their child’s death through a trial that yielded little but sorrow.
Seared in their consciousness are terrible images of the fair-haired little boy with the impish grin, the boy they named after a faithful Old Testament king. There was Josiah, asking what it feels like to die. There was Josiah, telling his mother jokes so she wouldn’t be so sad. There was Josiah, struggling to walk on the final day of his life, June 21, 1989, a Wednesday, the first day of summer.
“It’s been like trying to heal but you can’t,” Tim Alvarado said, as the jury deliberated. “They (Baxter Hyland lawyers) are just trampling over our son’s grave. You just want to stand up and scream and yell at them and say: ‘Maybe this doesn’t mean anything to you. You get to go home and play with your children and watch them grow. But what do we have? We have nothing. Our lives are destroyed.’ ”
Now that they know Joan Alvarado carries the hemophilia gene, the couple has decided against having other children. Although they sometimes talk about adoption, they feel they must first get Josiah’s death behind them.
“I’m stuck in the reliving,” Joan Alvarado said. “I don’t have a happy memory of my son. All I see is the pain, the suffering.”
As she spoke, she hugged her own slender frame, wrapping her empty arms tightly around her waist. Since Josiah died, she explained, she does not know quite what to do with them.
If there is a bitter irony in the story of Josiah and the thousands of other hemophiliacs with HIV, it is this: The very product that has cut their lives short revolutionized the treatment for their age-old disorder, holding the promise that for the first time, hemophiliacs could live a normal life.
Contrary to popular belief, people with hemophilia do not bleed faster, nor do they die from simple cuts or scrapes. They bleed longer, because their plasma, a blood component, is missing proteins--called “factors"--that facilitate clotting. Those with Hemophilia A, the most common form, lack Factor 8. Those with Hemophilia B, which afflicted Josiah, lack Factor 9.
Internal bleeding from bumps and bruises, especially head injuries, is the biggest danger. Nonetheless, as recently as four decades ago, many hemophiliacs made it past childhood. Those who lived longer often suffered crippling deformities in the knees, ankles and other joints where blood pooled.
But the image of the hemophiliac as a frail, homebound child is outdated because of dramatic advances in treatment since the 1950s, when blood transfusions were the only option. Transfusions were ineffective and dangerous; huge volumes of blood were required to get a small amount of clotting factor, and patients sometimes suffered heart failure as a result.
Then came fresh frozen plasma, until the 1960s when--after a freezer failure in which the plasma turned to slush--scientists discovered that clotting factor could be separated from plasma. But the resulting “cryoprecipitate” was slow to administer and difficult to store, and patients often suffered severe bleeding by the time they got to the hospital for treatment.
In the 1970s came factor concentrate--a freeze-dried form of Factor 8 and Factor 9, packaged in tiny vials of powder that were mixed with saline solution. It was convenient, stable and easy to use.
No longer would patients have to rush to the emergency room; they could be treated at home. Even better, the factor concentrates could be given prophylactically. A hemophiliac could play soccer or any other sport; he or his parents would infuse the factor in advance.
“It was a revolution in quality of life,” said Dr. Peter Smith, a hemophilia expert at Brown University. “Once you had a portable, practical, easily stored factor, people could pop that in their car. They could go on vacations when they never dared to do that.
“Fathers could move onto a different job because they knew how to treat their child. Mothers could get a job themselves because they didn’t always have to worry, waiting for the call from school that something had happened to Johnny.”
Factor concentrate so dramatically altered the outlook for hemophiliacs that in 1981, when the Alvarados learned their infant son suffered from the disorder, a nurse told them that if he had to pick a disease for his own child, he would choose hemophilia because it was so easy to treat.
So the Alvarados followed the medical mantra of the day: Treat early and often.
But there was a problem with the concentrate: Unlike cryoprecipitate, which was drawn from a single donor, Factor 8 and Factor 9 were drawn from the pooled plasma of up to 20,000 donors.
Most donors were paid; some were prisoners, others lived on Skid Row. Lawyers for the Alvarados say Baxter should have known that taking plasma from such high-risk groups was dangerous. Baxter attorney Rick Berkman counters: “Nobody ever said that poor people transmit AIDS.”
As important as who the plasma came from was that it came from so many people, any one of whom could taint the entire batch.
Indeed, by the late 1970s it was clear that the concentrates were transmitting disease--not AIDS, which no one knew about, but a new strain of hepatitis later known as Hepatitis C. The concentrate was so rife with hepatitis that, in experiments at the CDC, scientists used Factor 8 to infect chimps.
Still, the U.S. Food and Drug Administration did not yank the factor off the shelves; the prevailing sentiment was that the benefits outweighed the risk. This baffles Dr. Donald Francis, the former CDC official who has been lionized for his unsuccessful efforts to make the blood supply safe in the early days of the AIDS epidemic.
“Here you had this stuff that was filthy and yet was allowed to go through,” Francis said. “We knew that this stuff infected every single person who used it (with hepatitis). I guess that was acceptable when you thought the disease was mild.”
The experience with hepatitis looms large in the legal wrangling over whether the pharmaceutical companies did enough to keep their products clean.
In 1981--three years before the AIDS virus was discovered--a German firm patented a method of heat-treating the concentrate to rid the factor of hepatitis. But U.S. manufacturers did not employ the method. They argued that such treatments--which involved heating the concentrate to at least 148 degrees Fahrenheit for 24 to 144 hours--altered the composition of the factor so that it could no longer be produced in large enough quantities to meet patient needs.
Had they done so, many hemophiliacs would have been spared. Heat-treating, the companies later learned, kills HIV.
Moreover, hepatitis was prevalent among homosexuals, who were also at risk for AIDS. Although there was no AIDS test in the epidemic’s early days, lawyers for the Alvarados say that if a donor had hepatitis, he probably carried the AIDS virus too. They say Baxter should have questioned donors more thoroughly about their sexual practices, and should have tested plasma for hepatitis antibodies as a “surrogate marker” for AIDS.
But Baxter never used the surrogate test. Arthur Grebow, a lawyer for the Alvarados, says the company was too cheap to use it. “They knew they’d have to go out and replace the donors,” he said, “and that was going to be costly.”
Berkman, the Baxter attorney, counters with studies showing that hepatitis was not a good marker for AIDS. Moreover, he says, the antibodies served a useful purpose--they helped kill off any active hepatitis virus that slipped into the concentrate. And, he says, the FDA never required the test.
“If you get past the smears and go to the hard data,” Berkman said, “there is no evidence that anything we did caused this boy to be infected.”
Caught in the middle of this lawyers’ duel are the Alvarados. They are a quiet couple who live in an apartment not far from the Beverly Center. Joan, 42, recently took a job as a paralegal for Grebow’s firm; Tim, 39, repairs home security systems.
They came to Grebow a year after Josiah died, on the recommendation of a friend. Unlike Berkman, who works for a high-powered Philadelphia firm and recites medical terms with the fluency of a doctor, Grebow knew nothing of AIDS or hemophilia. He is a business lawyer, and his partner is a tax attorney. They knew only that the Alvarados had a tragic story, and so they agreed to take the case on contingency.
Winning required convincing a jury of two points: that Baxter was negligent by accepting prison plasma, failing to use the hepatitis surrogate test and not screening donors effectively; and that Baxter’s product--and not one manufactured by another company--infected Josiah.
It was this last point that tripped up the jury, according to both sides.
Joan Alvarado kept a meticulous infusion log; each time she gave Josiah factor concentrate, she noted the date, the lot number of the product and the name of the manufacturer. The log for the first five months of 1984--when the Alvarados believe their son was infected--lists only one product: Baxter Hyland Lot 2808 X018 AA.
During the trial, two top AIDS experts--Dr. Michael Gottlieb, who identified the earliest AIDS cases, and Dr. Steven Miles of UCLA--testified that Josiah was almost certainly infected between February and April, 1984. It was then, the doctors said, that Josiah exhibited the acute flu-like symptoms that appear when blood “seroconverts"--becomes HIV-positive.
Baxter countered with evidence that Josiah showed similar symptoms earlier, and the jury apparently could not agree on the date of infection. On Aug. 17, after four days of deliberations, they voted in favor of the defense.
The Alvarados and their lawyers were stunned.
“To me,” Joan Alvarado said, “it seems like they have gotten away with murder.”
Few hemophiliacs have been infected with the AIDS virus since 1985, when the test to detect it was developed. There have been no seroconversions since 1987, according to the National Hemophilia Foundation.
Since then, there has been another round of improvements in the manufacturing of factor concentrate: At the minimum, products are heat-treated and go through other purification processes. And there is an even safer way to make Factor 8, through genetic engineering. This new “recombinant” factor, available since December, 1992, is expensive--infusions can cost $100,000 a year or more, depending on the patient. But it is risk-free because no plasma--and hence, no donor--is required to make it.
So amid the disappearance of one generation of hemophiliacs, the outlook for the next has never been brighter.
“It’s a very exciting time, actually,” said Dr. Jonathon Goldsmith, who directs the Hemophilia Comprehensive Care Center at Childrens Hospital Los Angeles. “Something good has come out of the tragedy.”
But the biggest excitement of all is gene therapy, which Goldsmith says could be available within the next decade. If experiments--some of which are being conducted by Baxter Hyland--bear fruit, there would be no more need for Factor 8 and Factor 9.
After a decade of death, there would be a cure.
Hemophilia and AIDS
AIDS has taken a devastating toll on people with hemophilia; half of the estimated 20,000 hemophiliacs in the United States are infected with the human immunodeficiency virus as a result of tainted blood products. By 1984, AIDS had been diagnosed in 103 people with hemophilia, and 98 of them had died. The following chart shows how many new AIDS cases were reported each year, and how many of those patients have since died. Hemophiliacs diagnosed with AIDS in a given year: Patients diagnosed in that year who have subsequently died 1985 / 136: 129 1986 / 221: 199 1987 / 333: 303 1988 / 410: 332 1989 / 392: 280 1990 / 421: 250 1991 / 495: 213 1992 / 585: 118 1993* / 131: 4 * NOTE: Data is through June 30, 1993. Reporting for recent years is incomplete, and deaths for all years are underestimated because of underreporting.
SOURCE: U.S. Centers for Disease Control and Prevention.