Date: Wed, 15 Dec 2004 16:41:21 -0800


AP Exclusive: Woman Died During AIDS Study

10 minutes ago   Health - AP

By JOHN SOLOMON and RANDY HERSCHAFT, Associated Press Writers

A pregnant Tennessee woman who enrolled in federally funded research in
hopes of saving her soon-to-be-born son from getting AIDS (news - web
sites) died last year when doctors continued to give her an experimental
drug regimen despite signs of liver failure, government memos say.

Family members of Joyce Ann Hafford say the 33-year-old HIV (news - web
sites)-positive woman died without ever holding her newborn boy. They also
said they never were told the National Institutes of Health (news - web
sites) concluded the drug therapy likely caused her death.

The family first learned of NIH's conclusions when The Associated Press
obtained copies of the case file this month. For the past year, they say
they were left to believe Hafford, of Memphis, Tenn., 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."

Documents show Hafford's case reverberated among the government's top
scientists in Washington, who were monitoring reports of her declining
health in late July 2003 as she lay on a respirator.

NIH officials quickly suspected the drug regimen because it included
nevirapine, a drug known to cause liver problems, and the case eventually
reached the nation's chief AIDS researcher.

"Ouch! Not much wwe (we) can do about dumd (dumb) 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.

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, officials said.

"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 doctors there referred a call seeking comment to NIH.

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

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 drug effects 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.


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 sixth page, where it
said liver inflammation was possible and "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

"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.

Fishbein, who is seeking federal whistleblower protection after raising
concerns about NIH's practices, told AP that Hafford's death is
attributable to a bigger problem in government research.

"This is not just a clinical trial issue this is a healthcare issue. The
public expects that diagnostic test results are promptly evaluated and
acted on, if need be," Fishbein said. "Sadly, this is but one example where
an assessment was not done quickly and it cost this young mother her life."

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.


On the Net:

Documents gathered by AP for this story are available at:

National Institutes of Health:

Fishbein's whistleblower Web site: