Weeks before President George W. Bush announced a plan to protect African babies from AIDS, top US health officials were warned that research on the key drug was flawed and may have underreported 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 US.
But the National Institutes of Health, the government's premier 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 Tramont, reported on 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.
Records for NIH's nevirapine research in Uganda were so sloppy that NIH investigators couldn't be sure which mothers got the drug. They had to use blood samples to confirm doses, the documents show.
Less than a month after Bush announced a US$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. Africa accounts for more than two-thirds of the world's AIDS cases, with 27 million infected.
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.
Because of the problems, NIH shut down the Uganda research for 15 months, from the spring of 2002 to the summer of last year, to review the science and take corrective actions.
NIH officials said 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 US standards. The NIH has spent millions in the last two years improving its safety monitoring and record-keeping.
Senate Finance Committee Chairman Charles Grassley has asked the Justice Department to investigate NIH's conduct.
One lesson already learned 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.