AP Exclusive: Woman Died During AIDS Study
HIV Tampa Bay Owner/Webmaster (StPeteSean)
By JOHN SOLOMON and RANDY HERSCHAFT, Associated Press Writers
Joyce Ann Hafford died without ever holding the son she had tried to
save from AIDS by taking an experimental drug regimen administered by
government-funded researchers during her pregnancy.
But even before her stunned family could grieve, the death of the
33-year-old Memphis, Tenn., woman was reverberating among the
government's top scientists in Washington. They quickly realized the
drugs she was taking likely caused the liver failure that killed her.
Reports of her declining health were being monitored in late July 2003
at the National Institutes of Health as she lay on a respirator, and
the case eventually reached the nation's chief AIDS researcher,
according to documents obtained by The Associated Press.
"Ouch! Not much we can do about dumd docs," Dr. Edmund Tramont, NIH's
AIDS Division chief, responded in an e-mail after his staff reported
that doctors continued to administer the drugs nevirapine and Combivir
to Hafford despite signs of liver failure.
Nevirapine is an antiretroviral AIDS drug used since the mid-1990s, and
the government has warned since at least 2000 that it could cause
lethal liver problems or rashes when taken in multiple doses over time.
Hafford's family says they were never told NIH had concluded that the
experimental drug regimen likely caused her death until AP gave them
copies of NIH's internal case documents this month. They were left to
believe Hafford had died from AIDS complications but began pursuing
litigation to learn more.
"They tried to make it sound like she was just sick. They never
connected it to the drug," said Rubbie King, Hafford's sister.
"If it were the disease, solely the disease, and the complications
associated with the disease, that would be more readily acceptable than
her being administered medication that came with warnings that the
medical community failed to get ... to her."
NIH officials acknowledge that experimental drugs, most likely
nevirapine, caused her death, and that keeping the family in the dark
was inappropriate. But NIH usually leaves disclosures like that to the
doctors who treated her.
"We feel horrible that something like this would happen to anyone in
any circumstance," said Dr. H. Clifford Lane, NIH's No. 2 infectious
disease specialist. "There are risks in research and we try to minimize
them."
Jim Kyle, a lawyer representing Regional Medical Center in Memphis
where Hafford died, declined comment because of the family's pending
litigation.
The study during which Hafford died recently led researchers to
conclude that nevirapine poses risks when taken over time by certain
pregnant women. "Continuous nevirapine may be associated with increased
toxicity among HIV-1 infected pregnant women" with certain liver cell
counts, the study concluded.
Lane said Hafford should have signed a 15-page, NIH-approved consent
form at the start of the experiment specifically warning her of the
risks of liver failure. The family says Hafford seemed unaware of the
liver risks. They even kept the bottle of nevirapine showing it had no
safety warnings.
"My daughter didn't know any of the warning signs," said Rubbie Malone,
Hafford's mother and now caretaker of Hafford's new baby and older son.
"She never got to hold her baby."
Lane confirmed the nevirapine bottle Hafford received likely wouldn't
have had safety warnings because the experiment's rules called for the
patient to be unaware of the exact drugs being taken to avoid patient
influence on the test results. That means the consent form would have
been her lone warning about potential liver problems, he said.
And that 15-page, single-spaced consent form is chock full of complex
medical terms like "hypersensitivity reactions" and "pharmacokinetic
test." The warning about potential liver problems shows up on the 6th
page, where it said liver inflammation was possible and that it "rarely
may lead to severe and life threatening liver damage and death."
Hafford, who was HIV-positive but otherwise healthy, agreed to
participate in the NIH-funded research project that provided her
multiple doses of nevirapine, also known as Viramune, to protect her
soon-to-be-born son, Sterling, from getting HIV at birth.
The project was an outgrowth of earlier research in Africa that
concluded the drug could be taken in single doses safely to protect
newborns half the time.
"She didn't want her baby to be born with HIV infection if it could be
prevented at any cost," said King, her sister.
Hafford died Aug. 1, 2003, less than 72 hours after giving birth.
Sterling was delivered prematurely by Caesarean section as his mother
was dying. Though premature, he was spared from HIV and is healthy.
NIH's documents suggest Hafford's life might also have been spared if
the drug had been stopped when the first liver problems showed up in
her blood work two weeks before death.
"This case was particularly unfortunate b/c (because) the PI (principle
investigative doctor) didn't stop drug when grade 3 liver enzymes were
reported," Dr. Jonathan Fishbein, NIH's chief of good research
practices, told Tramont in an August 2003 e-mail.
NIH's official review determined the Memphis hospital failed to react
to lab results that showed her liver failure was starting well before
she died. "The site had identified that there was a delay in reviewing
laboratory evaluations from the clinic visit the week before she
presented with clinical hepatitis," an Aug. 15, 2003, report concluded.
The official investigative files cited "drug-induced hepatitis" of the
liver as the cause of death.
As is routine after a research-related death, NIH ordered changes to
the rules its researchers followed in the nevirapine studies to ensure
the early detection of liver problems, the memos show.
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