Nevirapine, the anti-HIV drug that already killed many
pregnant women in Uganda

(see: "NIH was warned in '02 on AIDS drug for Africa
" )http://www.boston.com/news/world/africa/articles/2004/12/14/nih_was_warned_in_02
_on_aids_drug_for
_africa?mode=PF

... and here: http://www.datelinehealth-africa.net/betav1.0/news/detailnews.asp?news_id=12110

... and the same flawed logic has now killed at least
one pregnant Black woman in Tennessee.

Alex

http://www.cnn.com/2004/HEALTH/conditions/12/16/aids.drug.death.ap/

Memos: Drug therapy killed HIV patient
Family led to believe illness caused her death
Thursday, December 16, 2004 Posted: 3:35 PM EST (2035 GMT)

Joyce Hafford died while participating in a federally funded research
program for HIV-positive patients.

(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.