Associated Press - December 14, 2004

But the National Institutes of Health never told the White House about problems it found in 2002 with its research on the drug nevirapine before U.S. President George W. Bush unveiled a $500 million plan to distribute the medicine across Africa, documents obtained by The Associated Press show.

Instead, officials inside the government's premier health research agency scrambled to keep its safety experts' concerns from scuttling the use of nevirapine in Africa as a cheap solution to stopping babies from getting AIDS from infected mothers, the memos show.

"Everyone recognized the enormity that this decision could have on the worldwide use of nevirapine to interrupt mother-baby transmission," NIH's AIDS research chief, Dr. Edmund C. Tramont, reported March 14, 2002, to his boss, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

Since then, hundreds of thousand of doses of the drug have been administered to African mothers and babies under the Bush plan.

Up to half those babies may have been stopped from getting AIDS, officials said. But now concerns are emerging about whether patients who received those single doses have developed resistance to further AIDS treatment.

The documents show Tramont and other NIH officials dismissed the problems with the nevirapine research in Uganda as overblown and were slow to report safety concerns to the Food and Drug Administration.

A professional auditor hired by NIH who first helped disclose the problems said in an interview that most of the problems were fixable but NIH officials were in a rush to declare that things were OK.

"It seemed to me we were drawing conclusions too quickly across the board, especially the implementation of nevirapine in South Africa," auditor Michael Hensley told AP.

Ultimately, NIH did stop the Uganda research for 15 months - from the spring of 2002 to the summer of 2003 - to review the science and take corrective actions.

NIH officials told AP they remain confident after re-reviewing the Uganda study and other research that nevirapine can be used safely in single doses by African mothers and children to prevent HIV transmission during birth.

But they acknowledged their Uganda research failed to meet required U.S. standards and have asked the National Academy of Sciences to investigate.

"I would say there are many lessons that we have learned from this review that will help us do our clinical research, both domestically and internationally, much better," said Dr. H. Clifford Lane, NIH's No. 2 infectious disease official.

The White House said it remains confident in Bush's $500 million plan in 2002 to send nevirapine to Africa, a continent that accounts for more than two-thirds of the world's AIDS cases, with 27 million people infected. The U.S. approved $2.9 billion to fight global AIDS in 2005.

"We want to make sure that people in need are getting the help they need," Press Secretary Scott McClellan said Tuesday. "The president is firmly committed to combatting the AIDS pandemic, particularly in the most afflicted areas of the world and that's why we're moving forward on the president's emergency relief plan."

Though the White House was never told of the problems, they were serious enough that the U.S. Health and Human Services Department sent a nine-page letter to Ugandan officials identifying violations of federal patient protection rules by NIH's research.

The NIH research "may have represented a failure to minimize risk to the subjects," the Office of Human Research Protections told Ugandan authorities in summer 2002, a month after Bush's announcement of the nevirapine announcement.

NIH officials said a recent closer review of the Uganda research has identified a new concern - that even single doses of nevirapine can create instant resistance. That means patients may not be able to use the drug or others in its class again when their AIDS worsens, Lane said.

"It was unexpected, and what it means is nevirapine probably shouldn't be a drug of first choice if other options are available," Lane said.

Lane said NIH officials were aware in spring 2002 of the impending White House announcement on nevirapine but did not tell presidential aides of the problems because they were confident, even before reviewing the Uganda research, that the underlying science was solid.

Nevirapine is an antiretroviral drug marketed in the U.S. as Viramune. It has been used since the 1990s to treat adult AIDS patients and is known to have potentially lethal side effects like liver damage and severe rashes when taken over time.

In 1997, NIH began studying in Uganda whether it could be given safely in single doses to stop mother-to-baby HIV transmission. That research showed it could reduce transmission in as many as half the births.

But by early 2002, an NIH auditor, the agency's medical safety experts and the drug's maker all disclosed widespread problems about the U.S.-funded research in Uganda.

Boehringer Ingelheim (BRI.YY), the Connecticut-based company that makes nevirapine, told NIH it identified at least one "critical compliance issue" that compromised the integrity of the study and more than four dozen issues it described as serious and major.

Boehringer and NIH auditors cited concerns such as failing to get patients' consent about changes in the experiment, administering wrong doses and delays and underreporting of "fatal and life threatening" problems.

"It appeared likely, in fact, that many adverse events and perhaps a significant number of serious adverse events for both mother and infant may not have been collected or reported in a timely manner," Westat Corp. found in March 2002. Westat is a medical auditing firm hired by NIH to visit and audit the Uganda site.

Westat reported there were 14 deaths not reported in the study database as of early 2002 and that the top two researchers in Uganda acknowledged thousands of bad reactions that weren't disclosed.

NIH said the subsequent review whittled that list down significantly, all deaths were eventually recorded and the majority of bad reactions are believed to have been caused by the poor health of patients, not the single dose of nevirapine. But they conceded it was incumbent on a U.S. research project to disclose them fully and quickly.

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