Memos: Drug therapy killed HIV patient

Family led to believe illness caused her death

(AP) -- A pregnant Tennessee woman who enrolled in federally funded research in
hopes of saving her soon-to-be-born son from getting AIDS 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-positive woman died
without ever holding her newborn boy. They also said they never were told the
National Institutes of Health 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, Tennessee, 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.

Family says victim unaware of risks

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 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 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.

Documents: Drug should have been stopped

Hafford died August 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
August 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.





Family led to believe illness caused her death

(AP) -- A pregnant Tennessee woman who enrolled in federally funded research in
hopes of saving her soon-to-be-born son from getting AIDS 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-positive woman died
without ever holding her newborn boy. They also said they never were told the
National Institutes of Health 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, Tennessee, 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.

Family says victim unaware of risks

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 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 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.

Documents: Drug should have been stopped

Hafford died August 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
August 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.






Sandra Tara Balduf (Ane)

Frontline Hepatitis Awareness

Support for patients and educational materials

http://frontline-hepatitis-awareness.com

1-866-Hep-GoGo 866-437-4646




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