WASHINGTON – Weeks before President George W. Bush announced a plan to protect African babies from AIDS, top U.S. health officials were warned that research on the key drug was flawed and may have underreported thousands of severe reactions including deaths, government documents show.
The 2002 warnings about the drug, nevirapine, were serious enough to suspend testing for more than a year, let Uganda’s government know of the dangers and prompt the drug’s maker to pull its request for permission to use the medicine to protect newborns in the United States.
But the National Institutes of Health, the government’s main health research agency, chose not to inform the White House as it scrambled to keep its experts’ concerns from scuttling the use of nevirapine in Africa as a cheap solution, according to documents obtained by The Associated Press.
‘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.
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.
NIH’s nevirapine research in Uganda was so riddled with sloppy record keeping that NIH investigators couldn’t be sure from patient records which mothers got the drug. Instead, they had to use blood samples to confirm doses, the documents show. Less than a month after Bush announced a $500 million plan to push nevirapine across Africa to slow the AIDS epidemic, the 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.
Africa accounts for more than two-thirds of the world’s AIDS cases, with 27 million infected, and the United States sought to help slow the disease’s spread across the continent.
Nevertheless, 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 transmissions during birth. But they acknowledged their Uganda research failed to meet required U.S. standards.
As a result, NIH recently asked the National Academy of Sciences to investigate its science in the case, and has spent millions in the last two years improving its safety monitoring and record keeping.
‘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.
One lesson derived from a closer review of the Uganda research is that even single doses of nevirapine can create instant resistance, meaning 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 about 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.
The White House – though unaware of the NIH concerns – also remains confident in Bush’s $500 million plan in 2002 to send nevirapine to Africa. Bush approved $2.9 billion for global AIDS fighting next year.
‘The president’s mission is to try to stop the spread of AIDS in Africa and to come at it from a new angle, and that is what this is all about,’ spokesman Trent Duffy said.
Nevirapine is an antiretroviral drug marketed in the United States as Viramune that has been used since the 1990s to treat adult AIDS patients and is known to have potentially lethal effects like liver damage and severe rashes when taken over time.